1

IAOe?IIAEUeIA AEAAeAI?ss IAOE OE?A?IE

?INOEOOO O?C?IEIA?? ?i.I.I.AIAIIIEUeOess

EOOI?EIAA ??EIA AANEE?AIA

OAeE 612.35:612.014.3:615.015.44

AEA*AIIss O*ANO? I?IAeOEO?A IAOAAIE?CIO A?AO?AeIIIAI? EENEIOE O
OOIEOe?IIOAAII? AAIAOIOeEO?A UO??A A EOEUeOO?? OA EIEOEUeOO?? C
EE?OEIAIE EOIOA?A

Niaoe?aeuei?noue

03.00.13 — O?c?ieia?y ethaeeie ? oaa?ei

A A O I ? A O A ? A O

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

EE?A 1999 ?.

?iaioo aeeiiaii o a?aeae?e? ?ioiieia?? oa oeeoioiene/ieo ne?iaaoie

?inoeoooo o?c?ieia?? ?i. I. I. Aiaiiieueoey IAI Oe?a?ie

Iaoeiaee ea??aiee: aeieoi? a?ieia?/ieo iaoe,

Aeaen??aa ??eia Ieeiea?aia

?inoeooo o?c?ieia??
?i.I.I.Aiaiiieueoey IAI Oe?a?ie,

caa?aeoaa/ a?aeae?eo ?ioiieia?? oa
oeeoine?iaaoie

Io?oe?ei? iiiiaioe: aeieoi? a?ieia?/ieo iaoe,

AEae?ei Ethaia ?aai?aia

Oe?a?inueea Aeaaeai?y aea?aeaaiiai
oi?aae?iiy i?e

I?aceaeaioia? Oe?a?ie, i?ioani?
eaoaae?e aaeaieia??

eaiaeeaeao a?ieia?/ieo iaoe

Ia?/aiei Aaeeia ?aai?aia

?inoeooo o?c?ieia??
?i.I.I.Aiaiiieueoey IAI Oe?a?ie,

noa?oee iaoeiaee ni?a?ia?oiee
a?aeae?eo

aenia?eiaioaeueii? ea?ae?ieia??

I?ia?aeia onoaiiaa: Ee?anueeee oi?aa?neoao ?i.O.A.Oaa/aiea,

eaoaae?a o?c?ieia?? ethaeeie oa
oaa?ei

Caoeno a?aeaoaeaoueny “30”eenoiiaaea 1999 ?. i “14” aiaeei? ia
can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee Ae 26.198.01 i?e ?inoeooo?
o?c?ieia?? ?i.I.I.Aiaiiieueoey IAI Oe?a?ie ca aae?anith: 252024 Ee?a,
aoe.Aiaiiieueoey, 4.

C aeena?oaoe??th iiaeia iciaeiieoeny o a?ae?ioaoe? ?inoeoooo o?c?ieia??
?i.I.I.Aiaiiieueoey IAI Oe?a?ie

Aaoi?aoa?ao ?ic?neaiee “20”aeiaoiy 1999 ?.

A/aiee nae?aoa? niaoe?ae?ciaaii? a/aii? ?aaee,

aeieoi? a?ieia?/ieo iaoe
C.I.Ni?ie?ia-Ia??ia

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue oaie

Ia/?iea cae?enith? nai? /eneaii? ooieoe?? ye oe?e?nia nenoaia, yea
neeaaea?oueny c ??cieo aeae?a ee?oei, ui aca?iiae?thoue i?ae niaith
[Iayineee Ae.I., 1992; Uaaieaa A.E., 1992; Spitzer J., 1995].
Aaiaoioeeoe aeeiiothoue iniiai? iaoaaie?/i? ooieoe??, oae? ye i?aeo?eiea
a i?aai?ci? aiiainoaco aoaeaaiae?a, a?ee?a oa e?i?ae?a, aeaoieneeaoe?eio
oa aecie?eiio ooieoe??. Na?aae ee?oei niieo/ii? oeaieie eeth/iaa
iieiaeaiiy caeiathoue iae?ioaae ia/?iee (ee?oeie Eoioa?a) — ?
aeniei?aaeoeai? ee?oeie, a?ieia?/i? yeino? yeeo aa?”ththoue a oe?ieeo
iaaeao a caeaaeiino? a?ae eiie?aoii? neooaoe??, a oiio aiie iathoue
oi?eaeueio iiaeeea?noue ?aaaoaaoe oa ieoo?ai aeeth/aoeny a ?aaoeyoe?th
aiiainoaco ? ?icaeoie iaoieia?/iiai i?ioeano. Iieacaii, ui aaaeeeaeie
aiaeiaaiieie ?aaoeyoi?aie ooieoe?e ee?oei ia/?iee oa iaae?aoi?aie ?o
aca?iiae?? ? i?iaeoeoe iaoaaie?cio a?ao?aeiiiai? eeneioe, oeeoie?ie, NO.
Aooie?eiia oa ia?ae?eiia ?aaoeyoe?y ooieoe?e ee?oei ia/?iee, ii?yae c
ia?aiaeie oa aiaeie?eiieie aieeaaie, caaacia/o? ae?yeuei?noue oeueiai
i?aaio a o?c?ieia?/ieo oiiaao, a ?o ii?ooaiiy a oiiaao iaoieia?? ?
iaeiei c iaeaaaeeea?oeo iaoiaaiaoe/ieo iaoai?ci?a.

A?aeiii, ui ia/?iea neioaco? i?inoaaeaiaeeie oa eaeeio???ie c
a?ao?aeiiiai? eeneioe ca oeeeeiieneaaiaciei oa e?iieneaaiaciei oeyoaie
iaoaaie?cio, a?aeiia?aeii[Huber M., 1990; Hagmann W., 1991; Kawada N.,
1990; Meng X., 1994], a oaeiae ? iniiaiei i?aaiii ae?i?iaoe?? oa
aeaa?aaeaoe?? aeeicaii?ae?a nenoaiiiai iioiaeaeaiiy [Brass E., 1988;
Hagmann W., 1989; Keppler D., 1989; Leier I., 1992; Parthe S., 1990;
Stene D., 1988; Shirley M, 1990; Shirley M., 1992; Tran-Thi T., 1994;
Wettstein M., 1995; Wheelan P., 1995]. Ae?y i?inoaaeaiaeei?a ia ia/?ieo
aea/aia a a?eueo?e i???, i?ae eaeeio???i?a. Iieacaia o/anoue
i?inoaaeaiaeei?a a ?aaoeyoe?? aoaeaaiaeiiai iai?io oa aeayeeo ?ioeo
ooieoe?e aaiaoioeeo?a [Huber M., 1990; 4, Bjornsson O., 1992; Decker K.
1990; Kanemaki T., 1993; Mitkov D. 1990; Muschol W., 1991; Okumura T.,
1990; Plumley D., 1995; Satoh M., 1993], a oaeiae a ?aaoeyoe??
ooieoe?iiaeueiiai noaio iaia?aio?iaoicieo ee?oei ia/?iee [Callery M.,
1990; Georgakopoulos E., 1995; Goss J., 1993; Lysz T., 1990; Karck U.,
1989; Peters T., 1989; West M., 1993]. ? ie?ai? aeai? i?i aieea
eaeeio???i?a ia ooieoe?? ia/?iee a ii?i?, a naia ia i?ioeane nae?aoe??
aeia/? [Rodriguez-Ortigosa C., 1995]. I?e aeieeiaii? iioeiaeaeaiue
ia/?iee ci?ith?oueny iaoaaie?ci a?ao?aeiiiai? eeneioe. I?aeaeuaiiy ??aiy
eaeeio???i?a a ia/?ioe? aoei iieacaii ia oe?eiio ?yae? aeae?a ??
o?aaeaiiy in vivo, a aeieaaea neioaco eaeeio???i?a i?ecaiaeeea aei
nooo?aiai ciaioaiiy iioeiaeaeaiue, ui na?ae/eoue i?i o/anoue oeeo
iio?aeieo a?ao?aeiiiai? eeneioe a ?icaeoeo iaoieia?/iiai i?ioeano
[Kawada N., 1990; Meng X., 1994; Agha A., 1995; Gonzalez R., 1994;
Hiroichi N., 1989; Kawada N, 1990; Parry E. 1993; Reyes M., 1995].
Iieacaia oaeiae iaoiaaiaoe/ia ?ieue o?iiaienaio — i?iaeoeoo
oeeeeiieneaaiaciiai oeyoo iaoaaie?cio a?ao?aeiiiai? eeneioe. Eiai
eiioeaio?aoe?y i?aeaeuo?oueny i?e ae?? /ioe?eoei?enoiai aoaeaoeth ia
ia/?ieo in vivo oa ia eoeueoeaiaai? aaiaoioeeoe. Aaaaeaiiy ieoai
o?iiaienaio i?ecaiaeeei aei o?aaeaiiy ia/?iee, a aeieaaea ?aoeaioi??a
aei o?iiaienaio iiia?aaeaeaea ooeiaeaeaiiy [Meng X., 1994; Engin A.,
1995; Marinovich M., 1989; Nagai H., 1989]. Ii?yae c iaoiaaiaoe/iith
ae??th iaoaaie?o?a a?ao?aeiiiai? eeneioe aeyaeaia ? i?ioaeoeaia ae?y
oaeeo i?inoaaeaiaeei?a, ye IAA1, IAA2 oa i?inoaoeeee?i [Bang S., 1991;
Chamulitrat W., 1994; Chamulitrat W., 1995; Jones D., 1995; Kaminski D.,
1989; Lim S., 1995; Masaki N., 1992; Nakano H., 1994;Totsuka E., 1995;
Quiroga J., 1993]. I?ioaeoeaia /e ooeiaeaeoth/a ae?y aeeicaii?ae?a in
vivo iiaea aooe iia”ycaia c? ci?iaie i?e?ioee?eoeyoe??, c i?a?aoe??th oa
aeoeaaoe??th aai ?ia?a?oe??th iaeo?io?e?a, ae??th NO, ui iieacaii a
?yae? aeine?aeaeaiue [Fukumura D., 1996; Gaudio E., 1997; Herbert K.,
1989; Kurose I., 1996; Kurose I., 1997; Stadler J., 1995; Zhang B.,
1997], a oaeiae c i?yiei aieeaii aeeicaii?ae?a ia ooieoe?? ee?oei
ia/?iee, ui i?aeoe/ii ia aeine?aeaeaii. Aaeaeaaoiith iiaeaeeth aeey
aea/aiiy aaciina?aaeiuei? o/ano? aeeicaii?ae?a a ?aaoeyoe?? ooieoe?e
ee?oei ia/?iee ? eoeueoo?a ee?oei. Eoeueoeaoaaiiy ??cieo oei?a ee?oei
ia/?iee noi?nii aeicaiey? aea/aoe aca?iiae?th i?ae ieie. Aaaaeathoue, ui
a ia/?ioe? iniiaieie i?iaeooeaioaie aeeicaii?ae?a ? ee?oeie Eoioa?a
[Kuiper J., 1988; Mion F., 1995]. Inoaii?i /anii aeiaaaeaii, ui
aaiaoioeeoe oaeiae neioacothoue i?inoaaeaiaeeie oa eaeeio???ie, ye?
iiaeooue aeeiioaaoe ?ieue aooie?eiieo ?aaoeyoi??a [Huwyler J., 1990;
Otomo Y., 1993; Yu M., 1998]. Oaeei /eiii, i?aaenoaaey? iniaeeaee
?ioa?an aea/aiiy o/ano? aeeicaii?ae?a a aooi- oa ia?ae?eii?e ?aaoeyoe??
ooieoe?e aaiaoioeeo?a a eoeueoo?? oa eieoeueoo?? c ee?oeiaie Eoioa?a. Ia
no/aniiio aoai? ci?iai neioaco ?ioi?iaoe?eieo iieaeoe, a oiio /ene?
aeeicaii?ae?a, oa ii?ooaiith i?aeee?oeiii? aca?iiae?? iaaea?oueny
aaaeeeaa cia/aiiy a ?icaeoeo iaoieia?/ieo i?ioean?a o ia/?ioe?. Aeey
aeyaeaiiy ?ie? i?iaeoeo?a iaoaaie?cio a?ao?aeiiiai? eeneioe a
aenia?eiaio? oe?iei aeei?enoiao?oueny oa?iaeieia?/iee i?aeo?ae ?c
canoinoaaiiyi aeieaoi??a neioaco a?aeiia?aeieo aeeicaii?ae?a.

O ca”yceo c aeuaiaaaaeaiei oyaey?ony aeooaeueiei aea/aiiy aieeao
aeieaoi??a iaoaaie?cio a?ao?aeiiiai? eeneioe ia ooieoe?iiaeueiee noai
aaiaoioeeo?a, eoeueoeaiaaieo ie?aii oa noi?nii c ee?oeiaie Eoioa?a, a
ii?i? oa i?e ?o o?aaeaii?.

Ca”ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie

Oaia aeena?oaoe?? iia”ycaia c aeine?aeaeaiiyie, ye? aeeiiothoueny
a?aeae?eii ?ioiieia?? ? oeeoioiene/ieo ne?iaaoie ?inoeoooo o?c?ieia??
?i.I.I.Aiaiiieueoey IAI Oe?a?ie “Aea/aiiy o/ano? i?iaeoeo?a iaoaaie?cio
a?ao?aeiiiai? eeneioe o aca?iiae?? ?ioiieiiiaoaioieo ee?oei oa aioeo?e c
ee?oeiaie ia/?iee, na?oey, noaoaaeo caeic” (1993-1998??.).

Iaoa ? caaea/? aeine?aeaeaiiy

Aea/eoe aieea aeieaoi??a iaoaaie?cio a?ao?aeiiiai? eeneioe ia
ooieoe?iiaeueio aeoeai?noue aaiaoioeeo?a uo??a a eoeueoo?? oa
eieoeueoo?? c ee?oeiaie Eoioa?a a ii?i? oa i?e ae?? aaiaoioiene/iiai
aaaioo — /ioe?eoei?enoiai aoaeaoeth. Aeey aeinyaiaiiy iinoaaeaii? iaoe
aoee iinoaaeai? ne?aeoth/? caaaeaiiy:

1. Iaea?aeaoe oa ioa?aeoa?ecoaaoe ia?aeiio eoeueoo?o aaiaoioeeo?a oa ?o
eieoeueoo?o c ee?oeiaie Eoioa?a.

2. Aea/eoe ci?ie ooieoe?iiaeueiiai noaio aaiaoioeeo?a a eoeueoo?? oa
eieoeueoo?? c ee?oeiaie Eoioa?a a oiiaao aeieaaee e?iieneaaiace (ca
aeiiiiiaith ii?ae?a?ae?iaoay?aoiai? eeneioe) a ii?i? oa i?e ae??
/ioe?eoei?enoiai aoaeaoeth.

3. Aea/eoe ci?ie ooieoe?iiaeueiiai noaio aaiaoioeeo?a a eoeueoo?? oa
eieoeueoo?? c ee?oeiaie Eoioa?a a oiiaao aeieaaee oeeeeiieneaaiace (ca
aeiiiiiaith ?iaeiiaoaoeeio) a ii?i? oa i?e ae?? /ioe?eoei?enoiai
aoaeaoeth.

4. Aea/eoe ci?ie ooieoe?iiaeueiiai noaio aaiaoioeeo?a a eoeueoo?? oa
eieoeueoo?? c ee?oeiaie Eoioa?a a oiiaao aeieaaee o?iiaienaineioaoace
(ca aeiiiiiaith aaicee?i?aeacieo) a ii?i? oa i?e ae?? /ioe?eoei?enoiai
aoaeaoeth.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a

Aia?oa i?iaaaeaii eiiieaeni? aeine?aeaeaiiy ii aea/aiith aieeao
i?iaeoeo?a oeeeeiieneaaiace a ii??aiyii? c aieeaii i?iaeoeo?a
e?iieneaaiace ia aeeoo?caeaoi?noue, ooieoe?iiaeueio aeoeai?noue
i?oioiiae??e oa neioac na/iaeie a aaiaoioeeoao i?e ?o ie?aiiio oa
noi?niiio c ee?oeiaie Eoioa?a eoeueoeaoaaii?.

Aia?oa aeyaeaii, ui aeieaaea e?iieneaaiace i?ecaiaeeoue aei ci?i
iieaciee?a caaaeueieo oa?aeoa?enoee ooieoe?iiaeueiiai noaio aaiaoioeeo?a
— aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e oa
aeeoo?caeaoiino? ?ioaeoieo eoeueoo? aaiaoioeeo?a, a aeieaaea
oeeeeiieneaaiace ci?ith? niaoeeo?/io ooieoe?th aaiaoioeeo?a — neioac
na/iaeie.

Aia?oa iieacaia i?ioaeoeaia ae?y ii?ae?a?ae?iaoay?aoiai? eeneioe —
aeieaoi?a e?iieneaaiace oa i?ioaeoeaia ae?y aaicee?i?aeacieo — aeieaoi?a
o?iiaienaineioaoace a aeine?aeao in vitro ia aaiaoioeeoao,
eoeueoeaiaaieo ie?aii oa a eieoeueoo?? c ee?oeiaie Eoioa?a i?e o?aaeaii?
?o NNl4.

I?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a

?acoeueoaoe aeine?aeaeaiiy iathoue ooiaeaiaioaeueia cia/aiiy aeey
aeyaeaiiy aeayeeo iaoai?ci?a aooi- ? ia?ae?eiii? ?aaoeyoe?? ooieoe?e
ee?oei ia/?iee. A i?eeeaaeiiio aniaeo? iaea?aeai? aeai? aaaeeea? aeey
?icoi?iiy ?icaeoeo oiene/iiai o?aaeaiiy ia/?iee, iiina?aaeeiaaiiai
aeeicaii?aeaie, ui iaaeanoue iiaeeea?noue iaa?oiooaaoe iaoiaee aieeao ia
eiai ia?aa?a ca aeiiiiiaith aeei?enoaiiy niaoeeo?/ieo aeieaoi??a
iaoaaie?cio a?ao?aeiiiai? eeneioe.

Iniaenoee aianie caeiaoaa/a

I?e aeeiiaii? ?iaioe caeiaoaa/ai i?iaaaeaii iaoeiaee iiooe oa
iaa?oiooaaiiy aea?aiiai iai?yieo aeine?aeaeaiue. Aeeiiaii aenia?eiaioe
ii aea/aiith aieeao aeieaoi??a iaoaaie?cio a?ao?aeiiiai? eeneioe ia
aaiaoioeeoe a eoeueoo?? oa eieoeueoo?? c ee?oeiaie Eoioa?a. I?iaaaeaii
aiae?c iaea?aeaieo ?acoeueoao?a. Aenia?eiaioaeueia ?iaioa ii
iaea?aeaiith oa eoeueoeaoaaiith ee?oei i?iaaaeaia ni?eueii c
ni?a?ia?oieeaie a?aeae?eo ?ioiieia?? oa oeeoine?iaaoie ?inoeoooo
o?c?ieia?? ?i.I.I.Aiaiiieueoey IAI Oe?a?ie.

Ai?iaaoe?y ?acoeueoao?a aeena?oaoe??

Iniiai? iieiaeaiiy aeena?oaoe?? neooaee oa iaaiai?thaaee ia Ieaioi?
iaoeiai-iaaee/iiai oiaa?enoaa iaoio?c?ieia?a Oe?a?ie (Euea?a, 1993);
3-io I?aeia?iaeiiio neiiic?oi? “Nenoaiii-aioenenoaiiay ?aaoeyoeey a
aeeaie e iaaeeaie i?e?iaea” (Ee?a, 1993); 14-io c”?cae? Oe?a?inueeiai
o?c?ieia?/iiai oiaa?enoaa ?i.?.I.Iaaeiaa (Ee?a, 1994); OV c”?cae?
Oe?a?inueeiai o?c?ieia?/iiai oiaa?enoaa (Aeiiaoeuee, 1998); Ieaioi?
oiaa?enoaa iaoio?c?ieia?a Oe?a?ie (*a?i?aoe?, 1998).

Ioae?eaoe??

?acoeueoaoe aeena?oaoe?? aeeeaaeai? a 13 ioae?eaoe?yo: noaoo? — 4, oace
eiioa?aioe?e, n?iiiceoi?a, c”?cae?a, ieaioi?a — 9.

Ianya oa no?oeoo?a aeena?oaoe??

Aeena?oaoe?eia ?iaioa neeaaea?oueny ?c anooio, iaeyaeo e?oa?aoo?e, 3
?icae?e?a aeanieo aeine?aeaeaiue oa ?o iaaiai?aiiy, aeniiae?a, nieneo
aeei?enoaii? e?oa?aoo?e. ?iaioa aeeeaaeaia ia 131 noi??ioe?,
?ethno?iaaia 22 ?enoieaie ? oaaeeoeath. Nienie e?oa?aoo?e ioiieth? 280
aeaea?ae.

INIIAIEE CI?NO

Iaoa??aee ? iaoiaee

Ia”?eoii aeine?aeaeaiiy aoea ia?aeiia eoeueoo?a aaiaoioeeo?a, ee?oei
Eoioa?a oa ?o noi?nia eoeueoo?a. Aeey io?eiaiiy ee?oei ia/?iee aoee
aeei?enoai? aei?ine? naioe? uo??a e?i?? A?noa? ianith 170-180 a oa a
aeayeeo aenia?eiaioao (aeine?aeaeaiiy aeicicaeaaeii? ae?? aeieaoi??a) —
ieo? e?i?? NAA ianith 18-20 a. Aaiaoioeeoe (A) oa ee?oeie Eoioa?a (EE)
aeae?eyee ca aeiiiiiaith aeaioaoaiii? eieaaaiacii? ia?ooc?? c
iiaeaeueoei i/euaiiyi a a?aae??io? aonoeie Ia?eieo. Ee?oeie Eoioa?a
aeiaeaoeiai i/euaee ca aeiiiiiaith aaeaac??. Nooi?iue i/euaiiy
iaea?aeaieo o?aeoe?e aaiaoioeeo?a ioe?ithaaee ca ii?oieia?/ieie
iciaeaie, ee?oei Eoioa?a — ca aeiiiiiaith caaa?aeaiiy noniaic?? ee?oei
ia ia?ieneaeaco oa ianiaoeeo?/io anoa?aco.

Eoeueoeaoaaiiy ee?oei i?iaiaeeee a ia?iaeaieo eieaaaiii ieaioaoao aeey
eoeueoo? ee?oei (Sigma) a iiaeeaiiio na?aaeiaeu? RPMI 1640 c 15 iiieue
HEPES, 15 % aia??iiaeueii? oaey/i? ne?iaaoee oa aioea?ioeeaie (o 96-,
24- aai 6-eoieiaeo ieaioaoao a caeaaeiino? a?ae oiia aenia?eiaioo).
Iinaaeea ee?oei: 96-eoieiaee ieaioao — 4104 A ia eoieo oa 4105 EE ia
eoieo, 24-eoieiaee ieaioao — 1105 A ia eoieo oa 1106 EE ia eoieo,
6-eoieiaee ieaioao — 1106 A ia eoieo. *a?ac 3 aiaeeie i?ney iinaaeee
i?ee??ieai? aaiaoioeeoe a?aeieaaee oeyoii cai?ie na?aaeiaeua. Aeey
noi?niiai eoeueoeaoaaiiy aei aaiaoioeeo?a aeiaeaaaee ee?oeie Eoioa?a a
ni?aa?aeiioaii? 1:10. I?ney 18 aiaeei eoeueoeaoaaiiy i?e 37iN o aieia?e
eaia?? c 5 % NI2 ee?oeie a?aeieaaee, cai?ithaaee na?aaeiaeua ?ieoaaoe??
ia na?aaeiaeua RPMI 1640 aac aia??iiaeueii? oaey/i? ne?iaaoee ? ?inoe?io
oa cae?enithaaee a?aeiia?aei? aieeae, a naia: aeiaeaaaee
ii?ae?a?ae?iaoay?aoiao eeneioo (IAeAE) — aeieaoi? e?iieneaaiace;
?iaeiiaoaoeei (?IAe)- aeieaoi? oeeeeiieneaaiace; aaicee?i?aeacie (A?A) —
aeieaoi? o?iiaienaineioaoace (e?ioeaaa eiioeaio?aoe?y aeieaoi??a
neeaaeaea 210-5 iieue). ?ic/eiaiee a DMSO CCl4 aeiaeaaaee a eoeueoo?e
aaiaoioeeo?a oa eieoeueoo?e aaiaoioeeo?a oa ee?oei Eoioa?a aei e?ioeaai?
eiioeaio?aoe?? 5 iiieue /a?ac 30 oaeeei i?ney aeieaoi??a.

A?io?i?/iee aiae?c eoeueoo?aeueiiai na?aaeiaeua (aeoeai?noue
aeai?i-ai?iio?ainoa?ace a eoeueoo?aeueiiio na?aaeiaeu?, neioac na/iaeie
aaiaoioeeoaie, eiioeaio?aoe?y iaeiiiaiai ae?aeueaeaa?aeo, eiioeaio?aoe?y
NO2-) i?iaiaeeee ia i?ioyc? 24 aiaeei. Aeoeai?noue
aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aei??thaaee /a?ac 4 oa 24
aiaeeie eoeueoeaoaaiiy i?ney aieea?a.

Ii?oieia?/io ioe?ieo eoeueoo? i?iaiaeeee ca aeiiiiiaith na?oeiai?
i?e?ineii?? c aeei?enoaiiyi ?ia?n?eiiai ia”?eoeao ( o 100) ia o?eniaaieo
?cii?iiaiieii i?aia?aoao, caaa?aeaieo aco?-aiceiii ca ?iiaiianueeei.

Aeoeai?noue aeai?i-ai?iio?ainoa?ace (AEO) a eoeueoo?aeueiiio na?aaeiaeu?
aecia/aee eiei?eiao?e/iei iaoiaeii a i?e?iiiaeeo?eaoe?? [Ei?iaeei A.O.,
1965]. Aeoeai?noue AEO ae?aaeaee o iiieue i??oaaoo/aiaeie
eoeueoo?aeueiiai na?aaeiaeua.

Aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aaiaoioeeo?a
ioe?ithaaee ca aeiiiiiaith IOO-oanoo oa ae?aaeaee a oiiaieo iaeeieoeyo
(O.I.), ui a?aeiia?aeaee cia/aiith iioe/ii? aonoeie ?ic/eio oi?iacaio,
ooai?aiiai a eoeueoeaiaaieo aaiaoioeeoao (4104 ee?oei) ca iaeio aiaeeio,
1000 [Reichner J., 1995].

Eiioeaio?aoe?th na/iaeie a eoeueoo?aeueiiio na?aaeiaeu? aei??thaaee
eiei?eiao?e/iei iaoiaeii ca aeiiiiiaith oano-nenoaie “A?i-Ea-Oano”
(A?ii). E?euee?noue na/iaeie ae?aaeaee a iea/106 ee?oei.

Ia?aeenia ieeneaiiy e?i?ae?a ioe?ithaaee ca iaeiie/aiiyi a
eoeueoo?aeueiiio na?aaeiaeu? iaeiiai c e?ioeaaeo i?iaeoeo?a — iaeiiiaiai
ae?aeueaeaa?aeo — eiei?eiao?e/iei iaoiaeii a i?e?iiiaeeo?eaoe?? [Ohkawa
H., 1979].

I?iaeoeoe?th NO ioe?ithaaee /a?ac aecia/aiiy eiioeaio?aoe?? eiai
iaoaaie?oa — NO2- a eoeueoo?aeueiiio na?aaeiaeu? eiei?eiao?e/iei
iaoiaeii c aeei?enoaiiyi ?aaeoeaa A??nna [Archer S., 1993].

I?aaenoaaeai? aeai? ? ?acoeueoaoii o?ueio-oanoe iacaeaaeieo
aenia?eiaio?a aeey eiaeiiai iieacieea. A eiaeiiio aenia?eiaio? aieea
aeine?aeaeoaaieo ?a/iaei cae?enithaaee ia?aeaeueii a o?eie?eaoao
eoeueoo? ee?oei. Noaoenoe/ia ia?iaea iaoa??aeo i?iaaaeaia c ia/eneaiiyi
e?eoa??th Nouethaeaioa aeey ia? aeaieo [Ieaei E., 1960].

?ACOEUeOAOE AeINE?AeAEAIUe OA ?O IAAIAI?AIIss

I?iaaaeaia ii?oieia?/ia oa oeeoio?i?/ia ioe?iea aaiaoioeeo?a oa ee?oei
Eoioa?a na?ae/eoue, ui ee?oeie, aeei?enoai? aeey iaea?aeaiiy eoeueoo?,
iaee aenieee nooi?iue aeeoo?caeaoiino? oa /enoioe. Aeae?eai? ee?oeie
Eoioa?a aeaaaee ae?aaeaio niaoeeo?/io ?aaeoe?th ia ia?ea?i? oa?iaioe
ee?oei iae?ioaaaeueii-iiiioeeoa?iiai ?yaeo — ianiaoeeo?/io anoa?aco oa
ia?ieneaeaco. I?ney ii/aoeiaiai eoeueoeaoaaiiy ia?aeiia eoeueoo?a
aaiaoioeeo?a iaea aeaeyae iiiioa?o iie?aiiaeueieo ee?oei, yeo iiaeia
a?aeianoe aei eoeueoo? aeniei? u?eueiino?. Aaiaoioeeoe, eoeueoeaiaai? ia
i?ioyc? 24 aiaeei, caa??aaee ooieoe??, i?eoaiaii? ?i in vivo.

Ia iniia? aiae?co e?oa?aoo?e oa iaoeo aeine?aeaeaiue anoaiiaeaia
aoaeoeaia aeica aeieaoi??a e?iieneaaiaciiai oa oeeeeiieneaaiaciiai
oeyo?a iaoaaie?cio a?ao?aeiiiai? eeneioe — 2o10-5 iieue.

Ci?ie ooieoe?iiaeueii? aeoeaiino? ?ioaeoieo oa o?aaeaieo NNl4
aaiaoioeeo?a, eoeueoeaiaaieo ie?aii oa noi?nii c ee?oeiaie Eoioa?a i?ae
aieeaii aeieaoi??a iaoaaie?cio a?ao?aeiiiai? eeneioe ca
oeeeeiieneaaiaciei oa e?iieneaaiaciei

oeyoaie

Ci?ie aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e
aaiaoioeeo?a a eoeueoo?? ? eieoeueoo??

sse ?ioaa?aeueio oa?aeoa?enoeeo o?c?ieia?/iiai noaio aaiaoioeeo?a
ioe?ithaaee aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e ca
IOO-oanoii. ?acoeueoaoe, iaea?aeai? ca aeiiiiiaith IOO-oanoo,
ei?aeththoue c aeaieie niiaeeaaiiy ee?oeiaie eenith, iaea?aeaieie
iiey?ia?ao?/iei iaoiaeii, ui aea? ciiao aeei?enoiaoaaoe IOO-oano, ye
iieaciee i?oioiiae??aeueiiai aeeoaiiy [Klostergaard et.al., 1987].
I?oioiiae??aeueia aeeoaiiy ? iniiaiei, ii?yae c ae?eie?cii, i?ioeanii, a
oiae? yeiai aaia?o?oueny AOO, ui caaacia/o? aia?a??th aetheiiaiaaiac a
aaiaoioeeoao, neioac na/iaeie, neioac a?ee?a, ae?th AOOac oa ?io?. A
ii?i? aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e
eoeueoeaiaaieo ee?oei aoea: aaiaoioeeoe — 644, 897 (O.I.), aaiaoioeeoe a
eieoeueoo?? c ee?oeiaie Eoioa?a — 1096, 7512 (O.I.) /a?ac 4 oa 24
aiaeeie eoeueoeaoaaiiy, a?aeiia?aeii. Aeyaeaii, ui a i?enooiino? IAeAE
oeae iieaciee nooo?ai i?aeaeuo?oueny /a?ac 4 aiaeeie i?ney aieeao: a
eoeueoo?ao aaiaoioeeo?a c 644 aei 12310 (O.I.), a eieoeueoo?ao c 1096
aei 20515 (O.I.), ?0,01 a on?o aeiaaeeao. I?ney 24 aiaeei eoeueoeaoaaiiy
IAeAE i?eai?/oaaea aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa
i?oioiiae??e aaiaoioeeo?a, eoeueoeaiaaieo ie?aii c 897 (O.I.) a
?ioaeoieo ee?oeiao aei 302 (O.I.) i?e ae?? aeieaoi?a (?0,01). ?iia??ii,
aeayeee ??aaiue eaeeio???i?a oa ?ioeo i?iaeoeo?a e?iieneaaiace ?
iaiao?aeiei aeey o?eaaei? i?aeo?eiee ooieoe?iioaaiiy aaiaoioeeo?a, a
?ia?a?oe?y e?iieneaaiace ia i?ioyc? 24 aiaeei iiaea i?ecaiaeeoe aei
cieaeaiiy i?oioiiae??aeueii? aeoeaiino?. A oie aea /an, i?e noi?niiio
eoeueoeaoaaii? aaiaoioeeo?a oa ee?oei Eoioa?a ia aeyaeaii a??ia?aeiiai
cieaeaiiy aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e i?e
o?eaae?e aeieaae? e?iieneaaiace; oeae iieaciee a ?ioaeoieo eoeueoo?ao
noaiiaea 7512 O.I., i?e ae?? IAeAE ia i?ioyc? 24 aiaeei — 588. Oe? aeai?
na?ae/aoue, ui i?iaeoeoe e?iieneaaiace a?ae?a?athoue o?c?ieia?/io
aooi?aaoethth/o ?ieue ii a?aeiioaiith aei i?oioiiae??aeueiiai aeeoaiiy
aaiaoioeeo?a ?, oaeei /eiii, i?eeiathoue o/anoue a ?aaoeyoe??
ooieoe?iiaeueiiai noaio ?ioaeoieo ee?oei.

Ia aeyaeaii a??ia?aeieo ci?i aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa
i?oioiiae??e i?e ae?? ?IAe ia eoeueoeaiaai? ee?oeie a on? oa?i?ie
aeine?aeaeaiue. A?aenooi?noue ci?i oe??? caaaeueii-o?c?ieia?/ii?
oa?aeoa?enoeee eoeueoeaiaaieo ee?oei iiaea aooe iia”ycaia c oei, ui ?IAe
aeieo? neioac oe?eiai ?yaeo i?inoaaeaiaeei?a, na?aae yeeo ? ye
i?ioaeoeai?, oae ? iaoiaaiaoe/i?. Aeine?aee c aeieaaeith
o?iiaienaineioaoace ca aeiiiiiaith A?A, i?iaaaeai? a 24-aiaeeiiee
oa?i?i, iieacaee, ui A?A, ia a?aei?io a?ae ?IAe, i?aeaeuo? aeoeai?noue
aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e eoeueoeaiaaieo
aaiaoioeeo?a ia 25 % ii a?aeiioaiith aei ?ioaeoieo ee?oei, ?0,05.
Niinoa??aa?oueny aeayea i?aeaeuaiiy oeueiai iieacieea a eieoeueoo?? (ia
16 %). Oea na?ae/eoue i?i aooie?eiio down-?aaoethth/o ?ieue o?iiaienaio
ii a?aeiioaiith aei i?oioiiae??aeueiiai aeeoaiiy aaiaoioeeo?a.

Aeoiaey/e c anoaiiaeaii? in vivo iaoiaaiaoe/ii? ?ie? eaeeio???i?a, ie
aea/aee ae?th aeieaoi?a e?iieneaaiace a oiiaao oiene/iiai o?aaeaiiy
aaiaoioeeo?a /ioe?eoei?enoei aoaeaoeai. NN14 (5 iiieue) i?eai?/oaaa
aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e eoeueoo?
aaiaoioeeo?a ia 84 % /a?ac 4 aiaeeie oa ia 90 % /a?ac 24 aiaeeie i?ney
eiai canoinoaaiiy (?0,01). A eieoeueoo?? oeae iieaciee oaeiae
ciaiooaaany ia 88 % oa 73 % /a?ac 4 oa 24 aiaeeie, a?aeiia?aeii (?0,01,
ii a?aeiioaiith aei ?ioaeoieo ee?oei). Aeieaaea e?iieneaaiace ca
aeiiiiiaith IAeAE caiia?aaea aeeeeeaiiio NN14 ii?ooaiith ooieoe?e
i?oioiiae??e. Aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e
aaiaoioeeo?a, o?aaeaieo NN14, ca?eueooaaeinue a i?enooiino? IAeAE c 102
aei 816 (O.I.) ia 4 aiaeei? oa c 92 aei 6211 (O.I.) ia 24 aiaeei?
aeine?aeaeaiue (?0,01 a on?o aeiaaeeao). Aiaeia?/ia ea?oeia
niinoa??aaeany a oiiaao noi?niiai eoeueoeaoaaiiy. A i?enooiino? IAeAE
aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aaiaoioeeo?a a
eieoeueoo??, ia?iaeaieo NN14, i?aeaeuoaaeanue c 132 aei 13112 (O.I.) oa
c 205 aei 657 (O.I.) /a?ac 4 oa 24 aiaeeie aieeao aeieaoi?a,
a?aeiia?aeii (?0,01). Oe? aeai? a?aeiinii i?ioaeoeaii? ae?? IAeAE
iiaiaeaeothoueny c aeine?aeaie, i?iaaaeaieie in vivo, eiee aaaaeaiiy
oaa?eiai ?ia?a?oi??a neioaco eaeeio???i?a, cie?aia IAeAE, caiia?aaei
ooeiaeaeaiith ia/?iee NN14 [Reyes M., 1995; Perez-Alvarez V., 1993]. I?e
oeueiio nooo?ai cieaeoaaany aeo?ae oeeoicieueieo oa?iaio?a c
aaiaoioeeo?a, a oaeiae ??aaiue IIE a ia/?ioe?. Iaoiaaiaoe/ia ?ieue
eaeeio???i?a iieacaia a aaaaoueio aeine?aeaeaiiyo in vivo [Kawada N.,
1990; Agha A., 1995; Hiroichi N., 1989; McGuire G., 1996]. A oeueiio
aeiaaeeo ?o ae?y iiaea aooe iia”ycaia c aieeaii ia noaeeie, c caeo/aiiyi
iaeo?io?e?a. Iao? aeai? na?ae/aoue, ui i?iaeoeoe e?iieneaaiace iiaeooue
aaciina?aaeiuei cae?enithaaoe ooeiaeaeoth/ee aieea ia aaiaoioeeoe, aac
o/ano? nenoai i?aaio oa i?aai?cio. Iaeiei c iaoai?ci?a i?yii?
o?aaeoth/i? ae?? eaeeio???i?a /e ?ioeo i?iaeoeo?a e?iieneaaiace ia
aaiaoioeeoe i?e ?o i?aeaeuaiiio neioac? a oiiaao iaoieia?? iiaea aooe
i?eai?/aiiy i?oioiiae??aeueiiai aeeoaiiy ee?oei, ine?eueee aeieaaea
neioaco i?iaeoeo?a e?iieneaaiace, ca iaoeie aeaieie, i?ecaiaeeoue aei
iineeaiiy aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e
aaiaoioeeo?a.

I?e ae?? ?IAe a oiiaao canoinoaaiiy NN14 ia aoei aeyaeaii nooo?aeo ci?i
aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e. Ia a?aei?io
a?ae ?IAe, aeieaoi? o?iiaienaineioaoace — A?A i?iyaeya ae?aaeaio
i?ioaeoeaio ae?th, a?aeiiaethth/e cia/aiiy oeueiai iieacieea a
aaiaoioeeoao, eoeueoeaiaaieo ie?aii oa noi?nii c ee?oeiaie Eoioa?a
iaeaea aei ??aiy a ?ioaeoieo eoeueoo?ao (?0,05 ii a?aeiioaiith aei ae??
NN14). Oea na?ae/eoue i?i ooeiaeaeoth/o ae?th o?iiaienaio i?e oiene/iiio
o?aaeaii? eoeueoeaiaaieo ee?oei. Ia?aaaaeia a?eueo?noue aeaieo,
iia”caieo c aieeaii o?iiaienaio, io?eiai? a nenoai? in vivo. Iieacaii,
ui aeieaaea ?aoeaioi??a aei o?iiaienaio ia? i?ioaeoeaio ae?th [Meng X.,
1994; Engin A., 1995]. Io?eiai? iaie ?acoeueoaoe na?ae/aoue ia ei?enoue
oiai, ui aeieaoi? o?iiaienaineioaoace ia? i?ioaeoeaiee aieea i?e
aaciina?aaei?e ae?? ia aaiaoioeeoe, ui ia iiina?aaeeiaaia noaeeiieie oa
?ioeie ?aaeoe?yie.

A e?oa?aoo?? ? aeai? i?i oa, ui aeieaaea iaeiiai oeyoo iaoaaie?cio
a?ao?aeiiiai? eeneioe iiaea i?ecaiaeeoe aei iineeaiiai ooai?aiiy
i?iaeoeo?a ?ioiai oeyoo [Meng X., 1994; Griswold Don E., 1996].
Perez-Alvarez c ni?aaaoi?aie [Perez-Alvarez V., 1993] aaaaeathoue, ui
i?ioaeoeaia ae?y ?ia?a?oi??a neioaco eaeeio???i?a ia o?aaeaio ia/?ieo
/anoeiai iiina?aaeeiao?oueny ca?eueoaiiyi neioaco i?inoaaeaiaeei?a.
Iiaeia i?eionoeoe, ui IAeAE, ?ia?aoth/e e?iieneaaiaco, iineeth? neioac
i?inoaaeaiaeei?a, /anoeia c yeeo ? oeeoii?ioaeoeaieie, oiaoi caoeniee
aieea IAeAE iiina?aaeeiaaiee ae??th a?aeiia?aeieo i?inoaaeaiaeei?a. Ie,
iaeii/anii c aeieaaeith e?iieneaaiace ca aeiiiiiaith IAeAE, aeieoaaee
oeeeeiieneaaiaco ?iaeiiaoaoeeiii. Aeyaeaii, ui IAeAE ye naia ii nia?,
oae ? i?e aeei?enoaii? noi?nii c ?IAe iaea iaeiaeiao ae?th ia
aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aaiaoioeeo?a a
ii?i? oa i?e o?aaeaii? NN14, oiaoi ae?y IAeAE ia aaiaoioeeoe iia”ycaia
naia c i?eai?/aiiyi ooai?aiiy i?iaeoeo?a e?iieneaaiace, a ia c
iineeaiiyi neioaco i?inoaaeaiaeei?a.

Oaeei /eiii, iaaaaeai? ?acoeueoaoe aeyaeythoue a?aei?ii?noue ae??
aeieaoi??a e?iieneaaiace oa oeeeeiieneaaiace ia aeoeai?noue
aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aaiaoioeeo?a a eoeueoo??
oa eieoeueoo?? c ee?oeiaie Eoioa?a a ii?i? oa i?e o?aaeaii? NN14. IAeAE
nooo?ai ci?ithaaea oeae iieaciee, oiae? ye ?iaeiiaoaoeei i?aeoe/ii ia
aieeaaa ia iueiai. A?A, ia a?aei?io a?ae ?iaeiiaoaoeeio, iineethaaa
aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e a ii?i? oa i?e
o?aaeaii? NN14. Aoea aeyaeaia a?aei?ii?noue ae?? IAeAE ia ?ioaeoi? oa
NN14-o?aaeai? ee?oeie: aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa
i?oioiiae??e ?ioaeoieo aaiaoioeeo?a i?e ae?? IAeAE i?aeaeuoaaeanue a
4-aiaeeiiee oa?i?i oa cieaeoaaeanue a iiaeaeueoiio, oiae? ye a oiiaao
ae?? NN14, IAeAE iie?iooaaea ooieoe?iiaeueiee noai i?oioiiae??e
aaiaoioeeo?a a on? oa?i?ie aeine?aeaeaiiue. I?enooi?noue ee?oei Eoioa?a
a eoeueoo?? aaiaoioeeo?a caiia?aaea cieaeaiith aeoeaiino?
aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e i?e ae?? IAeAE ia i?ioyc?
24-aiaeei.

Ci?ie aeoeaiino? AEO a eoeueoo?aeueiiio na?aaeiaeu?

Aeoeai?noue oeeoicieueiiai oa?iaioo aaiaoioeeo?a AEO a eoeueoo?aeueiiio
noia?iaoaio? a?aeia?aaea? aeo?ae oa?iaioo c ee?oei a ?acoeueoao? ?o
ooeiaeaeaiiy. Iaioee ??aaiue AEO na?ae/eoue i?i a?eueoo
aeeoo?caeaoi?noue aaiaoioeeo?a a eoeueoo??. Ine?eueee a ia?aeii?e
eoeueoo?? aaiaoioeeo?a a?aeaoaa?oueny caeiiii??iee i?ioean iinooiiai?
aeaa?aaeaoe?? /anoeie ee?oei, c /anii niinoa??aa?oueny iinooiiaa
ca?eueoaiiy aeoeaiino? AEO a na?aaeiaeu?.

Iieacaii, ui aianaiiy IAeAE a eoeueoo?o aaiaoioeeo?a i?ecaiaeeei aei
ciaioaiiy ia 38 % aeoiaeo AEO c ee?oei /a?ac 24 aiaeeie (?0,01).
Cieaeaiiy aeoeaiino? AEO i?iyaeyeinue a noi?ni?e eoeueoo?? aaea /a?ac 4
aiaeeie i?ney aieeao (ia 29 % , ?0,05 ii a?aeiioaiith aei eiio?ieth), oa
aoei ae?aaeaiei /a?ac 16 oa 24 aiaeeie (?0,01 a iaio aeiaaeeao). Oe?
aeai? na?ae/aoue, ui i?iaeoeoe e?iieneaaiaciiai oeyoo iaoaaie?cio
a?ao?aeiiiai? eeneioe caeaoi? aaciina?aaeiuei ooeiaeaeoaaoe aaiaoioeeoe.
Ia aeyaeaii nooo?aeo ci?i aeoeaiino? AEO i?e ae?? ?IAe oa A?A ia
eoeueoeaiaai? aaiaoioeeoe oa eieoeueoo?o a o?c?ieia?/ieo oiiaao.

Aaaaeaiiy NN14 (5 iiieue) a eoeueoo?aeueia na?aaeiaeua i?ecaiaeeei aei
oiene/iiai o?aaeaiiy aaiaoioeeo?a a eoeueoo?? oa eieoeueoo?? c ee?oeiaie
Eoioa?a. Oea i?iyaeyeiny a i?aeaeuaii? aeoeaiino? AEO a noia?iaoaioao
aaiaoioeeo?a ia 88 %, ia 130 % oa 92 % /a?ac 4, 16 oa 24 aiaeeie,
a?aeiia?aeii (?0,01 ii a?aeiioaiith aei ?ioaeoieo ee?oei, a on?o
aeiaaeeao). A eieoeueeo?? oea i?aeaeuaiiy neeaaeaei 110 %, 119 % oa 120
% /a?ac 4, 16 oa 24 aiaeeie, a?aeiia?aeii (?<0,01 ii a?aeiioaiith aei ?ioaeoieo ee?oei). A oeeo oiiaao IAeAE i?iyaeyea ae?aaeaio i?ioaeoeaio ae?th, cieaeoth/e ??aaiue AEO a noia?iaoaioao eoeueoo? aaiaoioeeo?a oa ?o eieoeueoo? a on? oa?i?ie aeine?aeaeaiiy (aaiaoioeeoe - ia 44 %, 19 % oa 25 % /a?ac 4, 16 oa 24 aiaeeie, ?<0,05 ii a?aeiioaiith aei ee?oei, o?aaeaieo NN14; aaiaoioeeoe + ee?oeie Eoioa?a - ia 20 %, 41 % oa 45 % /a?ac 4, 16 oa 24 aiaeeie, a?aeiia?aeii, ?<0,05 ii a?aeiioaiith aei ee?oei, o?aaeaieo NN14). Aeoiaey/e c oeueiai iiaeia i?eionoeoe, ui IAeAE, cieaeoth/e ??aaiue aiaeiaaiieo i?iaeoeo?a e?iieneaaiace a aaiaoioeeoao, caiia?aa? ooeiaeaeoth/?e ?o ae??, ui i?iyaey?oueny a i?aeaeuaii? aeeoo?caeaoiino? eoeueoeaiaaieo aaiaoioeeo?a. Oaeei /eiii, a oiiaao iaoieia?? eaeeio???ie, iaiaaii, iiaeooue aaciina?aaeiuei cae?enithaaoe ooeiaeaeoth/ee aieea ia aaiaoioeeoe. ?IAe ia ci?ithaaa aeo?ae AEO c aaiaoioeeo?a. Oi/a ?ia?a?oe?y oeeeeiieneaaiace ca aeiiiiiaith ?IAe ia aeeeeeaea ci?i aeeoo?caeaoiino? o?aaeaieo aaiaoioeeo?a, aeieaaea ie?aii? eaiee oeueiai oeyoo - o?iiaienaineioaoace - ca aeiiiiiaith A?A iaea nooo?aee aoaeo. Iieacaii, ui A?A i?ecaiaeea aei ciaioaiiy ia 22 % aeoiaeo AEO c aaiaoioeeo?a, o?aaeaieo NN14, /a?ac 24 aiaeeie (?0,05). Cieaeaiiy aeoeaiino? AEO a noia?iaoaio? eieoeueoo? aeyaeyeiny aaea /a?ac 4 aiaeeie i?ney aieeao (ia 36 %, ?0,05 ii a?aeiioaiith aei aaiaoioeeo?a, o?aaeaieo NN14), oa aoei ae?aaeaiei ia 24-e aiaeei? ae?? A?A (ia 28 % ii a?aeiioaiith aei eieoeueoo?, o?aaeaieo NN14, ?0,05). Oaeei /eiii, aoea anoaiiaeaia a?aei?ii?noue ae?? aeieaoi??a e?iieneaaiace oa oeeeeiieneaaiace ia aeoeai?noue AEO a eoeueoo?aeueiiio na?aaeiaeu? ye a ii?i?, oae ? i?e o?aaeaii? NN14. IAeAE cieaeoaaea oeae iieaciee, oiae? ye ?IAe ?noioii ia aieeaaa ia iueiai. A oie aea /an A?A, aeieaoi? o?iiaienaineioaoace, cieaeoaaa aeoeai?noue AEO a eoeueoo?aeueiiio na?aaeiaeu? aaiaoioeeo?a oa eieoeueoo? a oiiaao ae?? NN14, ui na?ae/eoue i?i ooeiaeaeoth/o ae?th o?iiaienaio i?e aeieeiaii? oiene/iiai o?aaeaiiy. I?ioaeoeaia ae?y IAeAE oa A?A aoea a?eueo ae?aaeaiith a eieoeueoo?? aaiaoioeeo?a c ee?oeiaie Eoioa?a, i?ae a ie?aii eoeueoeaiaaieo aaiaoioeeoao oa i?iyaeyeany ?ai?oa. Ci?ie neioaco na/iaeie aaiaoioeeoaie Iaie ia aoei aeyaeaii nooo?aeo ci?i neioaco na/iaeie aaiaoioeeoaie i?e ae?? aeieaoi?a e?iieneaaiace IAeAE, o oie /an ye aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e ee?oei cia/ii ci?ithaaeanue. Oea na?ae/eoue i?i ni?yiiaaiee ?aaoethth/ee aieea, yeee iathoue i?iaeoeoe e?iieneaaiace ia ??ci? ooieoe?? aaiaoioeeo?a. Ia a?aei?io a?ae IAeAE, ?IAe cieaeoaaa neioac na/iaeie ia 30 % oa ia 20 % a ii?i? oa i?e o?aaeaii? NN14, a?aeiia?aeii (?0,05) i?e eiai ae?? ia i?ioyc? 24 aiaeei eoeueoeaoaaiiy. Oe? aeai? na?ae/aoue i?i oa, ui noia?iee aieea an?o i?iaeoeo?a oeeeeiieneaaiace i?ecaiaeeoue aei i?aeaeuaiiy neioaco na/iaeie, cae?enithth/e, oaeei /eiii, ?aaoeyoe?th aeaoieneeaoe?eii? ooieoe?? ia/?iee a ii?i? oa i?e iaoieia??. I?e ae?? ?ioiai aeieaoi?o iaoaaie?cio a?ao?aeiiiai? eeneioe ca oeeeeiieneaaiaciei oeyoii - A?A - oaeiae niinoa??aaeiny a??ia?aeia cieaeaiiy neioaco na/iaeie, oiaoi o?iiaienai, iaiaaii, a?a? up-?aaoethth/o ?ieue ii a?aeiioaiith aei niaoeeo?/ii? ooieoe?? aaiaoioeeo?a - neioaco na/iaeie. E??i oiai, iao? aeai? iieacothoue, ui ?ia?aoth/a ae?y ?IAe ia neioac na/iaeie a cia/i?e i??? iiina?aaeeiaaia cieaeaiiyi neioaco o?iiaienaio. Oaeei /eiii, aoei aeyaeaii iniaeeaino? ae?? aeieaoi??a e?iieneaaiaciiai oa oeeeeiieneaaiaciiai oeyo?a iaoaaie?cio a?ao?aeiiiai? eeneioe ia neioac na/iaeie aaiaoioeeoaie: IAeAE ia aieeaaa ia oeth ooieoe?th, oiae? ye ?iaeiiaoaoeei oa A?A i?eai?/oaaee ??. Aeyaeaii oaeiae aeeoa?aioe?eiaaio ae?th aeeicaii?ae?a ia ??ci? ooieoe?? aaiaoioeeo?a. Ci?ie ia?aeeniiai ieeneaiiy e?i?ae?a (IIE) Ae?y canoiniaaieo aeieaoi??a e?iieneaaiace oa oeeeeiieneaaiace ? a?aeiinii niaoeeo?/iith. Ca aeayeeie aeaieie, IAeAE oa ?yae ?ioeo aeieaoi??a iathoue aioeieneaeaioi? aeanoeaino?, oiaoi ciaioothoue ia?aeenia ieeneaiiy e?i?ae?a [Tang D., 1996]. Ie aeine?aeaeoaaee ci?ie ?ioaineaiino? i?ioean?a IIE ii iaeiie/aiith e?ioeaaiai i?iaeoeoo - iaeiiiaiai ae?aeueaeaa?aeo - a eoeueoo?aeueieo noia?iaoaioao a?ae aaiaoioeeo?a i?e ae?? IAeAE, ?IAe oa A?A. Oeae iieaciee ? ?ioi?iaoeaiei, ine?eueee iieacaii, ui 95 % IAeA iaeiie/o?oueny a ciai?oiueiee?oeiiiio na?aaeiaeu? eoeueoeaiaaieo aaiaoioeeo?a [Gunther T., 1995]. Iao? aeai? na?ae/aoue, ui an? aeei?enoai? aeieaoi?e cieaeothoue e?euee?noue IAeA a eoeueoo?aeueiiio na?aaeiaeu? a?ae aaiaoioeeo?a. Oi/a IAeAE, ?IAe oa A?A cieaeothoue e?euee?noue IAeA a no?aei?e i??? (ia 46 %, 37 % oa 27 %, a?aeiia?aeii), ci?ie aeoiaeo AEO c aaiaoioeeo?a oa aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aeyaeythoueny o?eueee i?e ae?? IAeAE oa A?A, a ci?ie neioaco na/iaeie - o?eueee i?e ae?? ?IAe oa A?A. Oe? aeai? na?ae/aoue, ui aieea aeei?enoaieo aeieaoi??a ia ooieoe?iiaeueiee noai aaiaoioeeo?a, a iniiaiiio, iaoiiaeaiee aeieaaeith neioaco a?aeiia?aeieo iio?aeieo a?ao?aeiiiai? eeneioe ? a cia/ii iaio?e i??? iia”ycaiee c i?eoaiaiieie aeieaoi?ai aioeieneaeaioieie aeanoeainoyie oa i?eai?/aiiyi IIE. I?iaeoeoe?y ieneaeo acioo ee?oeiaie Eoioa?a, eoeueoeaiaaieie ie?aii oa noi?nii c aaiaoioeeoaie Aeine?aeaeoth/e iaoai?cie ae?? aeieaoi??a iaoaaie?cio a?ao?aeiiiai? eeneioe, iaiao?aeii iaoe ia oaac?, ui oey ae?y iiaea aooe iiina?aaeeiaaia NO. Inoaii?i /anii oe?iei aeeneooo?oueny ieoaiiy i?i ?ieue NO a ooieoe?iioaaii? ia/?iee a ii?i? oa i?e iaoieia??. A aeine?aeao in vivo iieacaia ?iaeoeoe?y NO i?e o?aaeaii? ia/?iee ieoae NN14 [Rockey D., 1997]. Iieacaii, ui aeeeeeaia ee?oeiaie Eoioa?a i?oioiiae??aeueia aeenooieoe?y aaiaoiiieo ee?oei oa aaiaoioeeo?a iiina?aaeeiaaia, a cia/i?e i???, ae??th NO [Fukumura D., 1996; Herbert K., 1989; Kurose I., 1996]. ? aeai? i?i o?aaeoth/ee aieea NO ia aeeoaiiy i?oioiiae??e aaiaoioeeo?a uo??a in vitro [Fisch C., 1996]. Iieacaia ?nioaaiiy aca?iica”yceo i?ae neioacii aeeicaii?ae?a oa NO [Harbrecht B., 1996; Harbrecht B., 1997; Rosa M., 1996]. Aeoiaey/e c oeueiai, ie aaaaeaee aeioe?eueiei aeyaeoe iiaeeeao o/anoue NO a aoaeoao aeieaoi??a neioaco aeeicaii?ae?a. E??i oiai, Studler c ni?aaaoi?aie [Stadler J., 1995] iieacaee, ui a oiiaao i?aeaeuaiiai neioaco NO a aaiaoioeeoao ?ia?ao?oueny ooai?aiiy na/iaeie, ine?eueee a aeaiiio aeiaaeeo eaea iiaa i?i eiieo?aioe?th ca caaaeueiee noano?ao L-a?a?i?i. Aaaeeeai aoei anoaiiaeoe, /e iiina?aaeeiaaia ?ia?aoth/a ae?y ?IAe oa A?A ia neioac na/iaeie i?aeaeuaiith i?iaeoeoe??th NO. A ie?ai?e na??? aenia?eiaio?a ie aei??thaaee ??aaiue NO a eoeueoo?aeueiiio na?aaeiaeu? i?e ae?? aeieaoi??a ia eoeueoeaiaai? ee?oeie. I?iaeoeoe?y NO a ?ioaeoieo Eoioa??anueeeo ee?oeiao aoea iacia/iith oa neeaaeaea 0,660,13 iiieue/106 ee?oei. A noia?iaoaioao ie?aii eoeueoeaiaaieo aaiaoioeeo?a NO2- a aeaieo oiiaao ia aecia/aany. I?e noi?niiio eoeueoeaoaaii? aaiaoioeeo?a oa ee?oei Eoioa?a oeae iieaciee aoa iaaeeaeaiee aei e?eueeino? NO2- a ie?aii eoeueoeaiaaieo ee?oeiao Eoioa?a. Ia aeyaeaii a??ia?aeieo ci?i eiioeaio?aoe?? NO2- i?e ae?? IAeAE oa ?IAe, oiaoi aeyaeai? iaie aoaeoe aeieaoi??a e?iieneaaiace oa oeeeeiieneaaiace ia ooieoe?? aaiaoioeeo?a ia iiina?aaeeiaai? NO. Iniaeeaino? ci?i ooieoe?iiaeueiiai noaio aaiaoioeeo?a a oiiaao ?o eieoeueoeaoaaiiy c ee?oeiaie Eoioa?a Aea/aiiy ci?i ooieoe?iiaeueiiai noaio aaiaoioeeo?a, eoeueoeaiaaieo noi?nii c ee?oeiaie Eoioa?a i?e ae?? aeieaoi??a iaoaaie?cio a?ao?aeiiiai? eeneioe, aeicaiey? ioe?ieoe ia?ae?eiio ?aaoethth/o ?ieue i?iaeoeo?a, neioac yeeo aeieo?oueny, o ooieoe?iioaaii? aaiaoioeeo?a. Iao? aeine?aeaeaiiy iieacaee, ui ni?yiiaai?noue ci?i aeine?aeaeoaaieo iieaciee?a i?e ae?? IAeAE, ?IAe oa A?A aoea iaeiaeiaith ye a aaiaoioeeoao, eoeueoeaiaaieo ie?aii, oae ? a aaiaoioeeoao, eoeueoeaiaaieo noi?nii c ee?oeiaie Eoioa?a, a ii?i? ? i?e o?aaeaii? ee?oei NN14. Oea na?ae/eoue i?i oa, ui aeieaaea neioaco i?inoaaeaiaeei?a ? eaeeio???i?a a aaiaoioeeoao ? a ee?oeiao Eoioa?a i?ecaiaeeoue aei no?aeieo ?acoeueoao?a, oiaoi aooie?eii? oa ia?ae?eii? aoaeoe aeeicaii?ae?a iiae?ai?. Oi/a ci?ie iieaciee?a ooieoe?e aaiaoioeeo?a, eoeueoeaiaaieo ie?aii oa noi?nii c ee?oeiaie Eoioa?a, ye?nii ia a?ae??ciyeeny, ne?ae a?aei?oeoe oe?eee ?yae e?euee?nieo iniaeeainoae ae?? aeieaoi??a a eieoeueoo?? ii??aiyii c eoeueoo?ith aaiaoioeeo?a. Oae, i?ioaeoeaia ae?y IAeAE ia aeeoo?caeaoi?noue aaiaoioeeo?a a ii?i? aoea a?eueo ae?aaeaiith a eieoeueoo?? oa i?iyaeyeany ?ai?o - aaea a 4 aiaeeiiee oa?i?i aeine?aeaeaiiy. I?ioaeoeaia ae?y IAeAE oa A?A a oiiaao o?aaeaiiy NN14 aoea oaeiae a?eueo ae?aaeaiith i?e noi?niiio eoeueoeaoaaii?. Aaaeeeai a?aei?oeoe, ui noaoenoe/ii a??ia?aeiee ?ia?aoth/ee aoaeo IAeAE ia aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e o 24-aiaeeiiee oa?i?i aeine?aeaeaiiy aoa aeyaeaiee o?eueee a eoeueoo?? aaiaoioeeo?a. I?enooi?noue ee?oei Eoioa?a a eoeueoo?? aaiaoioeeo?a a aeaye?e i??? caiia?aaea cieaeaiith aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e. Iiyniaiiyi oeueiai yaeua iiaea aooe a?eueoa a eieoeueoo??, i?ae a eoeueoo??, e?euee?noue i?iaeoeo?a e?iieneaaiaciiai oeyoo iaoaaie?cio a?ao?aeiiiai? eeneioe, ye?, iaaii, i?eeiathoue o/anoue a i?aeo?eioe? ooieoe?iioaaiiy ee?oei. C ?ioiai aieo, ia?ae?eii? aieeae ee?oei Eoioa?a iiaeooue caaacia/oaaoe a?eueoo ?acenoaioi?noue aaiaoioeeo?a aei ae?? ciai?oi?o oaeoi??a. Oaeei /eiii, noeoii?noue io?eiaieo aeaieo na?ae/eoue i?i oa, ui i?iaeoeoe e?iieneaaiaciiai oa oeeeeiieneaaiaciiai oeyo?a iaoaaie?cio a?ao?aeiiiai? eeneioe i?eeiathoue o/anoue a aooi- oa ia?ae?eii?e ?aaoeyoe?? ooieoe?iiaeueiiai noaio aaiaoioeeo?a a ii?i?; aeieaaea e?iieneaaiace oa o?iiaienaineioaoace ia? i?ioaeoeaiee aoaeo ia aaiaoioeeoe, o?aaeai? /ioe?eoei?enoei aoaeaoeai. A E N I I A E E 1. I?inoaaeaiaeeie ? eaeeio???ie ? aaaeeeaeie ?aaoeyoi?aie ooieoe?e ia/?iee a o?c?ieia?/ieo oiiaao oa i?e aeieeiaii? iaoieia?/ieo i?ioean?a. A?eueo?noue aeine?aeaeaiue, iia”ycaieo c ae??th aeeicaii?ae?a, i?iaaaeai? in vivo, eiee ?o aieea iiaea aooe iiina?aaeeiaaiee ci?iaie ia i?aaiiiio ??ai?. Ieoaiiy i?i aaciina?aaei?e aieea i?inoaaeaiaeei?a ? eaeeio???i?a ia ooieoe?iiaeueiee noai ??cieo iiioeyoe?e ee?oei ia/?iee a ii?i? oa i?e iaoieia?? aea/aia iaaeinoaoiuei. 2. Aaeaeaaoiith iiaeaeeth aeey aea/aiiy aaciina?aaeiuei? o/ano? i?inoaaeaiaeei?a ? eaeeio???i?a a ?aaoeyoe?? ooieoe?iioaaiiy ??cieo iiioeyoe?e ee?oei ia/?iee ? eoeueoo?a ee?oei. Aeey aea/aiiy aooi- oa ia?ae?eiieo aieea?a aeeicaii?ae?a aeei?enoaee oa?iaeieia?/iee i?aeo?ae, a naia aieeaaee aeieaoi?aie ie?aieo eaiie iaoaaie?cio a?ao?aeiiiai? eeneioe (oeeeeiieneaaiace, e?iieneaaiace oa o?iiaienaineioaoace) ia aaiaoioeeoe, eoeueoeaiaai? ie?aii ? noi?nii c ee?oeiaie Eoioa?a a ii?i? oa i?e ?o o?aaeaii? NNl4. 3. Anoaiiaeai? iniaeeaino? ae?? aeieaoi??a iaoaaie?cio a?ao?aeiiiai? eeneioe ia ooieoe?iiaeueiee noai eoeueoeaiaaieo aaiaoioeeo?a uo??a. Aeieaoi? e?iieneaaiace IAeAE i?aeaeuo? i?oioiiae??aeueia aeeoaiiy aaiaoioeeo?a (ca aeaieie aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e) o 4-aiaeeiiee oa?i?i oa cieaeo? oeae iieaciee /a?ac 24 aiaeeie, i?aeaeuo? aeeoo?caeaoi?noue aaiaoioeeo?a (ca aeaieie aeoeaiino? AEO a eoeueoo?aeueiiio na?aaeiaeu?), aea ia aieeaa? ia neioac na/iaeie. Aeieaoi? oeeeeiieneaaiace ?IAe cieaeo? neioac na/iaeie a eoeueoeaiaaieo aaiaoioeeoao, a oie aea /an ia aeeeeea? nooo?aeo ci?i ?o aeeoo?caeaoiino? oa ooieoe?e i?oioiiae??e. 4. A oiiaao oiene/iiai o?aaeaiiy aeyaeaii i?ioaeoeaiee aoaeo IAeAE, yea cieaeo? ??aaiue AEO a eoeueoo?aeueiiio na?aaeiaeu? oa caiia?aa? i?eai?/aiith aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aaiaoioeeo?a, aeeeeeaiiio NNl4. ?IAe a oeeo oiiaao ia aieeaa? ia aeeoo?caeaoi?noue oa aeoeai?noue i?oioiiae??e aaiaoioeeo?a. 5. Noi?nia aeei?enoaiiy IAeAE oa ?IAe ia? o? ae aoaeoe, ui ? IAeAE naia ii nia?; oea na?ae/eoue, ui ae?y IAeAE ia aaiaoioeeoe ia iiina?aaeeiaaia i?aeaeuaiiyi neioaco i?iaeoeo?a oeeeeiieneaaiace i?e i?eai?/aii? e?iieneaaiace. 6. Anoaiiaeaii, ui A?A, aeieaoi? ie?aii? eaiee oeeeeiieneaaiaciiai oeyoo iaoaaie?cio a?ao?aeiiiai? eeneioe - o?iiaienaineioaoace, ci?ith? ooieoe?? aaiaoioeeo?a a ii?i?, i?aeaeuoth/e aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e oa cieaeoth/e neioac na/iaeie. Ia a?aei?io a?ae ?IAe, A?A i?iyaey? ae?aaeaio i?ioaeoeaio ae?th a oiiaao o?aaeaiiy NNl4, cieaeoth/e aeo?ae AEO oa i?aeaeuoth/e aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aaiaoioeeo?a. 7. Anoaiiaeaii, ui aeyaeai? iniaeeaino? ae?? aeieaoi??a ia eoeueoeaiaai? aaiaoioeeoe ia iiina?aaeeiaai? ci?iaie neioaco NO oa ci?iaie IIE. 8. I?eioeeiia? caeiiii??iino? ci?i iieaciee?a ooieoe?iiaeueii? aeoeaiino? aaiaoioeeo?a i?e ae?? aeieaoi??a ia eieoeueoo?o ni?aiaaeathoue c? ci?iaie a ie?aii eoeueoeaiaaieo aaiaoioeeoao, iaeiae i?ioaeoeaia ae?y IAeAE oa A?A a?eueo ae?aaeaia a eieoeueoo??. I?enooi?noue ee?oei Eoioa?a a eoeueoo?? aaiaoioeeo?a caiia?aa? cieaeaiith aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e eieoeueoeaiaaieo ee?oei i?ae aieeaii IAeAE ia 24 aiaeei? aeine?aeaeaiiy, ui na?ae/eoue i?i ia?ae?eii? noaa?e?coth/? aieeae ee?oei Eoioa?a ia aaiaoioeeoe. 9. Iaea?aeai? aeai? aeacothoue ia oa, ui i?iaeoeoe e?iieneaaiace ? aaaeeeaeie aooi- oa ia?ae?eiieie ?aaoeyoi?aie ooieoe?e aaiaoioeeo?a, ye? aieeaathoue ia ianiaoeeo?/i? iieacieee ooieoe?iiaeueii? aeoeaiino? ee?oei, oae? ye ?o aeeoo?caeaoi?noue oa aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e. A oie aea /an i?iaeoeoe oeeeeiieneaaiace, cie?aia o?iiaienai, i?eeiathoue o/anoue a ?aaoeyoe?? niaoeeo?/ii? ooieoe?? aaiaoioeeo?a, oaei? ye neioac na/iaeie. 10. Aeyaeaiee i?ioaeoeaiee aoaeo aeieaaee e?iieneaaiace oa o?iiaienaineioaoace a oiiaao o?aaeaiiy aaiaoioeeo?a NNl4 na?ae/eoue, ui i?iaeoeoe e?iieneaaiace oa o?iiaienaineioaoace iathoue aaciina?aaei?e ooeiaeaeoth/ee aieea ia aaiaoioeeoe i?e oiene/iiio o?aaeaii? ia/?iee, iaeiei c iaoai?ci?a ooeiaeaeaiiy iiaea aooe i?eai?/aiiy aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aaiaoioeeo?a. NIENIE IIOAE?EIAAIEO I?AOeUe CA OAIITH AeENA?OAOe?? Noaoo?: 1. Iaeiaii I.A., Eooi?eiaa ?.A., I?eiiaiei ?.?. O/anoue aiaeiaaiieo aeeicaii?ae?a a ooieoe?iiaeuei?e aeoeaiino? ee?oei ia/?iee ieoae a eoeueoo?? // Aeiiia?ae? IAI.- 1996.- ? 12.- N.176-179. 2. Eooi?eiaa ?.A., Ei?i?e/oe A.I., Iaeiaii I.A. Aieea /ioe?eoei?enoiai aoaeaoeth ia aaiaoioeeoe oa ee?oeie Eoioa?a a eoeueoo?? // A?niee A?eioea?e?anueeiai Aea?ae.aa?a?.oi?aa?n.-1998.- aei.6, /.2.-N.171-174. 3. Makogon N., Lushnikova I., Korneitchuk A., Alexeyeva I. Effects of nordihydroguaiaretic acid and indomethacin on the viability and functional activities of normal and carbon tetrachloride-injured rat hepatocytes cultured alone and with Kupffer cells // Acta Physiol. Pharmacol. Bulg.- 1998.-V.23, N 2.- P.33-38. 4. Iaeiaii I.A., Eooi?eiaa ?.A., Aeaen??aa ?.I., Ei?i?e/oe A.I. Aieea aeieaoi??a oeeeeiieneaaiace oa o?iiaienaineioaoace ia eoeueoeaiaai? aaiaoioeeoe uo??a a ii?i? oa i?e o?aaeaii? /ioe?eoei?enoei aoaeaoeai // Aenia?ei. oa ee?i?/ia o?c?ie. ? a?io?i?y.- 1999.- ? 2.- N.45-51 Oace: 1. Aeaen??aa ?.I., Iaeiaii I.A., Eooi?eiaa ?.A. Ci?ie neioaco AeIE, ?IE oa a?eea a eoeueoeaiaaieo ia?aio?iaoicieo oa iaia?aio?iaoicieo ee?oeiao ia/?iee i?e oiene/iiio oa ?ioiiiio ?o o?aaeaii? // A ei.: Ee?oeii? oa iieaeoey?i? iaoai?cie ?icaeoeo iaoieia?/ieo i?ioean?a.- Oac.aeii. Ieaioio iaoeiai-iaae.oia-aa iaoio?c?ieia?a Oe?a?ie (23-24 aa?aniy 1993 ?.), Euea?a.- 1993.- N.1. 2. Aeaenaaaa E.I., Iaaeiae/ N.E., Iaeiaii I.A., Eooieeiaa E.A. O/anoea oeceieiae/anee aeoeaiuo aauanoa, auaeaeyaiuo eeaoeaie ia/aie, a noeioeyoeee e eiaeaeoeee eiioiieiiiaoaioiuo eeaoie // A ei.: Nenoaiii-aioenenoaiiay ?aaoeyoeey a ii?ia e i?e iaoieiaee. - Iao/.o?oaeu 3-ai Iaaeaeoia?iaeiiai neii. “Nenoaiii-aioenenoaiiay ?aaoeyoeey a aeeaie e iaaeeaie i?e?iaea” (10-13 iiya?y, 1993), Eeaa.- 1993.- N.76-80. 3. Aeaen??aa ?.I., Iaeiaii I.A., Ii?oie/aiei A.A., Eooi?eiaa ?.A. Ci?ie aeoeaiino? ?ioiieiiiaoaioieo ee?oei i?ae aieeaii ?a/iaei, ui aeae?eythoue ia?aio?iaoici? oa iaia?aio?iaoici? ee?oeie ia/?iee // Oac.aeiiia?ae. 14 c”?cae? Oe?.o?c?ie.oia.?i.?.I.Iaaeiaa, Ee?a.- 1994.- N.181. 4. Makogon N., Pavlovich S., Bryzgina T., Martynova T., Lushnikova I. Cultivated intact and injured mice liver cells produce substances which change the proliferation of immune cells // 12-th European immunology meeting, Barcelona.- 1994.- ?.346. 5. Iaaeiae/ N.E., Ii?oie/aiei A.A., Eooieeiaa E.A., Iaeiaii I.A., Ieeiiaiei E.?. Aeeyiea eioaeoiuo e oiene/anee iia?aaeaeaiiuo eeaoie ia/aie a oneiaeyo aeieaaeu oeeeeiieneaaiacu e eeiieneaaiacu ia eiioiieiiiaoaioiua eeaoee // Oac.aeiee. ? ?inneene. Eiia?. ii iaoioeceieiaee n iaaeaeoia?.o/anoeai, (Iineaa, 17-19 ieo.).- 1996.- N.155-156. 6. Alexeyeva I., Makogon N., Lushnikova I., Nikonenko I. Lipoxygenase inhibitors influence viability and oxygen consumption of murine liver cells in primary culture // 10th International Confer. on prostaglandins and related Compounds, Vienna.- 1996.- ?.105. 7. Aeaen??aa ?.I., Iaeiaii I.A., Eooi?eiaa ?.A., Ei?iae/oe A.I. ?ieue aeeicaii?ae?a a aooie?eii?e oa ia?ae?eii?e ?aaoeyoe?? ooieoe?e ee?oei ia/?iee a eoeueoo?? // Oace aeiee. ia OO c”?cae? Oe?.o?c?ie.oia. (Aeiiaoeuee, 12-15 o?aaiy 1998 ?.), O?c?ie.aeo?i.- 1998.- O.44, ? 3.- N.181. 8. Aeaen??aa ?.I., A?eca?ia O.I., Aeaenthe E.?., Iaaeiae/ N.?., Iaeiaii I.A., Ia?oeiiaa O.A., Ii?oie/aiei A.A., Eooi?eiaa ?.A., Ei?i?e/oe A.I., Noo?ia A.N. ?ieue aeeicaii?ae?a a aooie?eii?e ? ia?ae?eii?e ?aaoeyoe?? ooieoe?e ee?oei ia/?iee oa ?ioiieiiiaoaioieo ee?oei ca oiia ia/?ieiai? iaoieia?? // Oace aeiee. ia Ieaioi? oia.iaoio?c?ieia?a Oe?a?ie (*a?i?aoe?, 20-22 o?aaiy 1998 ?.), O?c?ie.aeo?i.- 1998.- O.44, ? 4.- N.52. 9. Alexeyeva I., Makogon N., Lushnikova I., Korneitchuk A. The influence of arachidonic acid metabolism inhibitors on some functions of normal and carbon tetrachloride-injured rat hepatocytes culrured alone and with Kupffer cells // XIIIth International Congress of Pharmacology (Munchen, 26-31 July, 1998).- 1998.- ?.R 351. AIIOAOe??: Eooi?eiaa ?.A. Aea/aiiy o/ano? i?iaeoeo?a iaoaaie?cio a?ao?aeiiiai? eeneioe o ooieoe?iioaaii? aaiaoioeeo?a uo??a a eoeueoo?? oa eieoeueoo?? c ee?oeiaie Eoioa?a.- Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa a?ieia?/ieo iaoe ca niaoe?aeuei?noth 03.00.13 - O?c?ieia?y ethaeeie oa oaa?ei.- ?inoeooo o?c?ieia?? ?i.I.I.Aiaiiieueoey IAI Oe?a?ie, Ee?a, 1999. Aeine?aeaeoaaee aieea aeieaoi??a e?iieneaaiace - ii?ae?a?ae?iaoay?aoiai? eeneioe (IAeAE), oeeeeiieneaaiace - ?iaeiiaoaoeeio (?IAe) oa o?iiaienaineioaoace - aaicee?i?aeacieo (A?A) ia ooieoe?iiaeueiee noai aaiaoioeeo?a a eoeueoo?? oa eieoeueoo?? c ee?oeiaie Eoioa?a a ii?i? oa i?e o?aaeaii? CCl4. Iieacaii, ui IAeAE i?aeaeuo? aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e aaiaoioeeo?a, ui oa?aeoa?eco? i?oioiiae??aeueia aeeoaiiy, a 4-aiaeeiiee oa?i?i oa cieaeo? oeae iieaciee /a?ac 24 aiaeeie, i?aeaeuo? aeeoo?caeaoi?noue ee?oei (ca aeaieie aeoeaiino? AEO a eoeueoo?aeueiiio na?aaeiaeu?), aea ia aieeaa? ia neioac na/iaeie. A oiiaao o?aaeaiiy aaiaoioeeo?a /ioe?eoei?enoei aoaeaoeai IAeAE ia? i?ioaeoeaio ae?th - cieaeo? aeo?ae AEO c ee?oei oa caiia?aa? i?eai?/aiith aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e. Aoaeo a?eueo ae?aaeaiee a eieoeueoo?? aaiaoioeeo?a c ee?oeiaie Eoioa?a. ?IAe cieaeo? neioac na/iaeie a aaiaoioeeoao, aea ia aeeeeea? nooo?aeo ci?i ?o aeeoo?caeaoiino? ? aeoeaiino? aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e a ii?i? oa i?e o?aaeaii? CCl4. Anoaiiaeaii, ui A?A ci?ith? ooieoe?? aaiaoioeeo?a a ii?i?, i?aeaeuoth/e aeoeai?noue aeaeo?ii-o?ainii?oiiai eaioethaa i?oioiiae??e oa cieaeoth/e neioac na/iaeie, a oaeiae i?iyaey? ae?aaeaio i?ioaeoeaio ae?th a oiiaao o?aaeaiiy NNl4. Iaea?aeai? aeai? na?ae/aoue, ui aeeicaii?aee ? aaaeeeaeie aooi- oa ia?ae?eiieie ?aaoeyoi?aie ooieoe?e aaiaoioeeo?a a ii?i?, a oaeiae, ui i?iaeoeoe e?iieneaaiace oa o?iiaienaineioaoace, iaiaaii, iathoue aaciina?aaei?e ooeiaeaeoth/ee aieea ia aaiaoioeeoe i?e oiene/iiio o?aaeaii? ia/?iee. EETH*IA? NEIAA: aaiaoioeeoe, ee?oeie Eoioa?a, aeieaoi?e e?iieneaaiace, oeeeeiieneaaiace oa o?iiaienaineioaoace, /ioe?eoei?enoee aoaeaoeue. Eooieeiaa E.A. Eco/aiea o/anoey i?iaeoeoia iaoaaieecia a?aoeaeiiiaie eeneiou a ooieoeeiie?iaaiee aaiaoioeeoia e?un a eoeueoo?a e eieoeueoo?a n eeaoeaie Eoioa?a. - Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe ii niaoeeaeueiinoe 03.00.13 - Oeceieiaey /aeiaaea e aeeaioiuo. - Einoeooo oeceieiaee ei.A.A.Aiaiiieueoea IAI Oe?aeiu, Eeaa, 1999. I?iaeoeou iaoaaieecia a?aoeaeiiiaie eeneiou (yeeicaiieaeu) yaeythony aaaeiuie ?aaoeyoi?aie ooieoeee eeaoie ia/aie a oeceieiae/aneeo oneiaeyo e i?e aicieeiiaaiee iaoieiae/aneeo i?ioeannia, a oaeaea iaaeeaoi?aie iaaeeeaoi/iuo acaeiiaeaenoaee. Aieueoeinoai enneaaeiaaiee, iinayuaiiuo aeaenoaeth yeeicaiieaeia, i?iaaaeaiu in vivo, eiaaea eo aeeyiea iiaeao auoue iiin?aaeiaaii eciaiaieyie ia i?aaiiii o?iaia. Aii?in i iaiin?aaenoaaiiii aeaenoaee i?inoaaeaiaeeiia e eaeeio?eaiia ia ooieoeeiiaeueiia ninoiyiea ?acee/iuo iiioeyoeee eeaoie ia/aie a ii?ia e i?e iaoieiaee eco/ai iaaeinoaoi/ii. Aaeaeaaoiie iiaeaeueth aeey eco/aiey iaiin?aaenoaaiiiai aeeyiey i?inoaaeaiaeeiia e eaeeio?eaiia ia ooieoeee eeaoie ia/aie yaeyaony ia?ae/iay eoeueoo?a eeaoie. Aeey eco/aiey o/anoey i?iaeoeoia iaoaaieecia a?aoeaeiiiaie eeneiou a aooi- e ia?ae?eiiie ?aaoeyoeee ooieoeee aaiaoioeeoia a eoeueoo?a e eieoeueoo?a n eeaoeaie Eoioa?a a aeaiiie ?aaioa eniieueciaaee oa?iaeieiae/aneee iiaeoiae n i?eiaiaieai aeieaoi?ia: oeeeeiieneaaiacu - eiaeiiaoaoeeia (EIAe), eeiieneaaiacu - ii?aeeaeae?iaoay?aoiaie eeneiou (IAeAE) e o?iiaienaineioaoacu - aaiceeeieaeaciea (AEA). Aanue eiiieaen aicaeaenoaee aeieaoi?aie i?iaaaeai a oeceieiae/aneeo oneiaeyo, a oaeaea a oneiaeyo iia?aaeaeaiey eeaoie /aou?aooei?enoui oaea?iaeii (NNl4). Eciaiaiey ooieoeee ioaeaeueii eoeueoeae?oaiuo aaiaoioeeoia i?e aeaenoaee aeieaoi?ia iicaieytho noaeeoue ia o/anoee yeeicaiieaeia a aooie?eiiie ?aaoeyoeee ooieoeee eeaoie. Niaianoiia eoeueoeae?iaaiea aaiaoioeeoia n eeaoeaie Eoioa?a eniieueciaaii aeey eco/aiey o/anoey yeeicaiieaeia a ia?ae?eiiie ?aaoeyoeee. Ioeaieaaee aeecianiiniaiinoue aaiaoioeeoia ii auoiaeo a eoeueoo?aeueioth n?aaeo oeeoicieueiiai oa?iaioa - aeaieiaieiio?ainoa?acu (AEO), ieoioiiae?eaeueiia aeuoaiea ii aeoeaiinoe yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee (IOO-oano) e aeaoieneeaoeeiiioth ooieoeeth ii aeoeaiinoe neioaca ii/aaeiu. Iieacaii, /oi IAeAE iiauoaao aeoeaiinoue yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee aaiaoioeeoia /a?ac 4 /ana e nieaeaao yoio iieacaoaeue /a?ac 24 /ana iinea aicaeaenoaey. I?enoonoaea eeaoie Eoioa?a a eoeueoo?a aaiaoioeeoia i?aaeioa?auaao nieaeaiea aeoeaiinoe yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee i?e aeaenoaee IAeAE a 24 /aniaie n?ie enneaaeiaaiey, /oi naeaeaoaeuenoaoao i ia?ae?eiiii noaaeeece?othuai aeeyiee Eoioa?ianeeo eeaoie ia aaiaoioeeou. Aeieaaea eeiieneaaiacu iiauoaao aeecianiiniaiinoue eeaoie, ii ia aeeyao ia neioac ii/aaeiu. NCl4 aucuaaao iia?aaeaeaiea eoeueoeae?oaiuo aaiaoioeeoia, nieaeay aeoeaiinoue yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee e iiauoay auoiae AEO a eoeueoo?aeueioth n?aaeo. A oneiaeyo iia?aaeaeaiey aaiaoioeeoia /aou?aooei?enoui oaea?iaeii IAeAE ieacuaaao i?ioaeoeaiia aeaenoaea - i?aaeioa?auaao oaiaoaiea aeoeaiinoe yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee e nieaeaao auoiae AEO ec eeaoie. I?ioaeoeaiue yooaeo aieaa au?aaeai a eieoeueoo?a aaiaoioeeoia n eeaoeaie Eoioa?a. EIAe, iai?ioea, nieaeaao neioac ii/aaeiu, ii ia aucuaaao nouanoaaiiuo eciaiaiee aeecianiiniaiinoe e aeoeaiinoe yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee aaiaoioeeoia eae a ii?ia, oae e a oneiaeyo aeaenoaey NCl4. Onoaiiaeaii, /oi AEA, aeieaoi? ioaeaeueiiai caaia oeeeeiieneaaiaciiai iooe iaoaaieecia a?aoeaeiiiaie eeneiou, eciaiyao ooieoeee aaiaoioeeoia a ii?ia, iiauoay aeoeaiinoue yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee e nieaeay neioac ii/aaeiu, a oaeaea i?iyaeyao au?aaeaiiia i?ioaeoeaiia aeaenoaea i?e iia?aaeaeaiee aaiaoioeeoia NCl4. Iineieueeo nieaeaiea neioaca ii/aaeiu i?e aeaenoaee EIAe e AEA auei au?aaeaii a noiaeiie noaiaie, ii-aeaeeiiio, eiaeae?othuaa aeaenoaea EIAe ia yoo ooieoeeth aaiaoioeeoia a cia/eoaeueiie noaiaie iiin?aaeiaaii nieaeaieai neioaca o?iiaienaia. Iaie iieacaii, /oi iniaaiiinoe aeaenoaey aeieaoi?ia ia aaiaoioeeou a eoeueoo?a ia iiin?aaeiaaiu eciaiaieyie neioaca NO e ia?aeeniiai ieeneaiey eeieaeia. Iieo/aiiua aeaiiua naeaeaoaeuenoaotho, /oi i?iaeoeou eeiieneaaiaciiai iooe iaoaaieecia a?aoeaeiiiaie eeneiou yaeythony aaaeiuie aooi- e ia?ae?eiiuie ?aaoeyoi?aie ooieoeee aaiaoioeeoia, eioi?ua aeeytho ia iieacaoaee ooieoeeiiaeueiie aeoeaiinoe eeaoie, oaeea eae eo aeecianiiniaiinoue e aeoeaiinoue yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee. A oi aea a?aiy i?iaeoeou oeeeeiieneaaiacu, a /anoiinoe o?iiaienai, i?eieiatho o/aonea a ?aaoeyoeee niaoeeoe/aneie ooieoeee aaiaoioeeoia - neioaca ii/aaeiu. Auyaeaiiue i?ioaeoeaiue yooaeo aeieaaeu eeiieneaaiacu e o?iiaienaineioaoacu a oneiaeyo iia?aaeaeaiey eoeueoeae?oaiuo eeaoie NN14 naeaeaoaeuenoaoao, /oi i?iaeoeou eeiieneaaiacu e o?iiaienaineioaoacu ieacuaatho iaiin?aaenoaaiiia iia?aaeaeathuaa aeaenoaea ia aaiaoioeeou i?e oiene/aneii iia?aaeaeaiee ia/aie, iaeiei ec iaoaieciia eioi?iai iiaeao auoue oaiaoaiea aeoeaiinoe yeaeo?ii-o?ainii?oiie oeaie ieoioiiae?ee aaiaoioeeoia. EETH*AAUA NEIAA: aaiaoioeeou, eeaoee Eoioa?a, aeieaoi?u eeiieneaaiacu, oeeeeiieneaaiacu e o?iiaienaineioaoacu, /aou?aooei?enoue oaea?iae Lushnikova I.V. Effects of arachidonic acid metabolites on the functional activities of rat hepatocytes cultured alone and with Kupffer cells.- Manuscript. Thesis for a candidate’s degree by speciality 03.00.13 - physiology of human and animals.- Bogomoletz Institute of Physiology of the NAS of Ukraine, Kiev, 1999. In order to study the contribution of eicosanoids to the regulation of the functions of normal and carbon tetrachloride (CCl4) - injured liver cells, primary cultures of hepatocytes (HC) either alone or in coculture with Kupffer cells (KC) were exposed to lipoxygenase inhibitor (nordihydroguaiaretic acid - NDGA), cyclooxygenase inhibitor (indomethacin - IND) and thromboxane synthetase inhibitor (benzylimidazole - BIA) in the presence and absence of CCl4. NDGA addition decreased the ALT release from HC, increased the mitochondrial electron transport chain activity (ETC activity) at 4 h and decreased this parameter at 24 h. Treatment with CCl4 resulted in increased ALT release and decreased ETC activity in HC and their cocultures with KC. The addition of NDGA decreased ALT levels and increased ETC activity in CCl4-injured cells. Urea production (UP) was not significantly affected by NDGA. In contrast, addition of IND decreased UP by HC, and did not alter ALT release and ETC activity in control and CCl4-treated cells. BIA decreased ALT release from CCl4-injured hepatocytes, increased ETC activity in control and CCl4-injured cells and decreased urea production by cultured hepatocytes. These results indicate that arachidonic acid metabolites are involved in the regulation of HC functions. This work also shows that a protective action of lipoxygenase and thromboxane synthetase inhibitors on CCl4-injured liver is mediated, at least in part, by their direct effects on HC, in particular by increasing the mitochondrial activity. KEY WORDS: hepatocytes, Kupffer cells, lipoxygenase, cyclooxygenase and thromboxane synthetase inhibitors, carbon tetrachloride

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