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Механізми дії хлориду ртуті та хлориду кобальту на активність delta-амінолевулінатсинтази в печінці щурів: Автореф. дис… канд. біол. наук / Т.В. Бар

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I?I?NOA?NOAI INA?OE OE?A?IE

OA?E?ANUeEEE AeA?AEAAIEE OI?AA?NEOAO

Aa?aii?e Oaoyia Aieiaeeie??aia

OAeE 577.151.04:57.044:546(492+732)

IAOAIICIE AeI? OEI?EAeO ?OOOI OA

OEI?EAeO EIAAEUeOO IA AEOEAIINOUe

(-AIIIIEAAOEIIAONEIOACE A IA*IIOeI UO?IA

03.00.04– A?io?i?y

AAOI?AOA?AO

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

Oa?e?a – 1999

Aeena?oaoe??th ? ?oeiien. ?iaioo aeeiiaii ia eaoaae?? a?io?i??
Oa?e?anueeiai aea?aeaaiiai oi?aa?neoaoo I?i?noa?noaa ina?oe Oe?a?ie.

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

Eae?iai Iaaei Aaenaio?eiae/,

caa?aeoaa/ eaoaae?ith a?io?i??

Oa?e?anueeiai aea?aeaaiiai oi?aa?neoaoo

I?i?noa?noaa ina?oe Oe?a?ie

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

*a/ioe?i Ieaen?e Aaneeueiae/,

caa?aeoaa/ eaoaae?ith o?i?? oa a?io?i??

Oa?e?anueeiai ciiaaoa?eia?iiai ?inoeoooo

I?i?noa?noaa ina?oe Oe?a?ie

aeieoi? a?ieia?/ieo iaoe,

noa?oee iaoeiaee ni?a?ia?oiee,

Ia?nueeee ?aaai Ao?i?iiae/, i?ioani? ca eaoaae?ith o?c?ieia?? ethaeeie
oa oaa?ei Oa?e?anueeiai aea?aeaaiiai oi?aa?neoaoo I?i?noa?noaa ina?oe
Oe?a?ie

I?ia?aeia onoaiiaa ?inoeooo a?io?i?? ?i. I.A.Iaeeaae?ia IAI Oe?a?ie
(a?aeae?e a?io?i?? eioa?iaio?a), i.Ee?a.

Caoeno a?aeaoaeaoueny ” 07 ” ea?oiy 1999 ?. i 1515 aiaeei? ia
can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee E 64.051.17 i?e Oa?e?anueeiio
aea?aeaaiiio oi?aa?neoao? I?i?noa?noaa ina?oe Oe?a?ie ca aae?anith:
310077, Oa?e?a, ie.Naiaiaee, 4, aoae.III-15.

C aeena?oaoe??th iiaeia iciaeiieoenue o Oeaio?aeuei?e iaoeia?e
a?ae?ioaoe? Oa?e?anueeiai aea?aeaaiiai oi?aa?neoaoo I?i?noa?noaa
ina?oe Oe?a?ie ca aae?anith: 310077, Oa?e?a-77, ie.Naiaiaee, 4.

Aaoi?aoa?ao ?ic?neaiee 1999 ?.

A/aiee nae?aoa? niaoe?ae?ciaaii? a/aii? ?aaee eaiaeeaeao a?ieia?/ieo
iaoe, noa?oee iaoeiaee ni?a?ia?oiee

Iaaeaeei A.?.

Caaaeueia oa?aeoa?enoeea ?iaiOE

Aeooaeuei?noue oaie. Oe?iea aeei?enoaiiy aaaeeeo iaoae?a a ae?iaie/eo
oe?eyo, ca?eueoaiiy ia’?io ?o aeiaoaaiiy oa ia?a?iaee ni?e/eieee
inoaii?i /anii cia/ia iaeiie/aiiy aaaeeeo iaoae?a oa ?o niieoe a
iaaeieeoiueiio na?aaeiaeu? [O?aooaiaa?a E.I., Eieanieeia A.N., Eoeiaaiei
A.I., 1994]. Iaaeeeoeiaa iaaeoiaeaeaiiy iaoae?a aei i?aai?cio ethaeeie
oa oaa?ei aeeeeea? ??ciiiai?oi? ooieoe?iiaeuei? oa iaoaaie?/i?
ii?ooaiiy [Iineaeaa TH.E., 1985; A?oia TH.A., Ieaoaiaaa O.A., 1989], o
oiio /ene? iia’ycai? c a?ineioacii aaio oa aaiii?ioa?i?a [Marks G.,
1985]. ?icaeoie oiene/ieo ii?o???e oa cieaeaiiy ai?noo ee?oeiieo
aaiii?ioa?i?a i?ae aieeaii nieae aaaeeeo iaoae?a a cia/i?e i??? ?
iane?aeeii ii?ooaiiy ?aaoeyoe?? eeth/iaiai oa?iaioo a?ineioaco aaio
(-ai?iieaaoe?iaoneioace (EO 2.3.1.37) [Rimington C., 1989]. Anoaiiaeaii,
ui nie? eiaaeueoo, ieaoeie, i?eaeth aai cae?ca aeeeeeathoue aeaiooaci?
ci?ie aeoeaiino? (-ai?iieaaoe?iaoneioace ((-AEE-neioace) a ia/?ioe?
nnaaoe?a: cieaeaiiy a ia?o? aiaeeie ? iiaeaeueoa i?aeaeuaiiy [Maines
M.D., 1984; Eaeeiai I.A., Aaeiaaoeeay E.A., 1986]. Iaeiae iaoai?cie ye
aaeueioaaiiy, oae ? ?iaeoeoe?? ?iiaie iaoae?a eeth/iaiai oa?iaioo
a?ineioaco aaio caeeoathoueny ia i?iyniaieie. Ia aea/aii oaeiae aieea
ia (-AEE-neioacio aeoeai?noue iai?aai?/ieo niieoe ?ooo?, ai?no yeeo a
iaaeieeoiueiio na?aaeiaeu? cia/ii ca?eueoeeinue [O?aooaiaa?a E.I.,
Ei?ooi I.I., 1990].

Ii?yae c i?yiith ?ia?aoth/ith ae??th ia neioac aai aeoeai?noue
(-AEE-neioace, nie? aaaeeeo iaoae?a iiaeooue aeeeeeaoe i?aeaeuaiiy a
ee?oeiao ia/?iee eiioeaio?aoe?? a?eueiiai aaio [Eaeeiai I.A. e ae?.,
1996; Ieeeo/aiei E.A. e ae?., 1998], ui ? iniiaiei ?aaoeyoi?ii
aeoeaiino? (-AEE-neioace [May B.K. et al., 1990; Ades I.Z., 1990;
Lathrop J.T., Timko M.P., 1993], aea aeaea?aea iaeiie/aiiy aaio ia
anoaiiaeai?. Aeooaeueiith i?iaeaiith a oeueiio ieai? iinoa? iiooe
iiaeeeaeo oeyo?a caiia?aaiiy aaiie?co i?ae aieeaii aaaeeeo iaoae?a c
iaoith aeeeth/eoe iaaei??ia iaaeoiaeaeaiiy aaio a ia/?ieo c e?ia’yiiai
?oneo. Aeiaeaoeiaei iaoai?ciii ae?? ?ii?a Co2+, Zn2+, Sn2+ ia
(-AEE-neioaco iiaea c’yaeoenue oi?ioaaiiy iaoaeiii?o??eiiaeo
eiiieaen?a, oei /anii ye ?iie Hg2+, Pb2+, Ni2+, Pt2+ oa ?io? ia
caeaoi? cai?uoaaoe Fe2+ a aaiii?ioa?iao [Maines M.D., 1984]. Aeacai?
?ica?aeiino? aeanoeainoae ?ii?a eiaaeueoo oa ?ooo?, ii?yae c ?o oe?ieei
aeei?enoaiiyi a i?aeoe/i?e ae?yeueiino? ethaeeie oa cia/iei
?iciianthaeaeaiiyi a ciai?oiueiio na?aaeiaeu? [O?aooaiaa?a E.I.,
Eieanieeia A.N., Eoeiaaiei A.I., 1994], iaoiiaeee aea?? oeeo iaoae?a
aeey aeine?aeaeaiiy.

A?aoiaoth/e aeuaaeeeaaeaia, anoaiiaeaiiy iaoai?ci?a ae?? oei?eaeo ?ooo?
oa oei?eaeo eiaaeueoo ia aeoeai?noue eeth/iaiai oa?iaioo a?ineioaco
aaio, (-AEE-neioace, a ia/?ioe? nnaaoe?a c’yaey?oueny aeooaeueiei oa
ia?niaeoeaiei a ieai? iiaeaeueoi? ?ic?iaee ?aeiiaiaeaoe?e uiaei
e?eoaaiiy aino?eo io?o?iue nieyie aaaeeeo iaoae?a oa oiene/ieo ii?o???e.

Aca?iica’ycie aeaii? ?iaioe c iaoeiaeie i?ia?aiaie. Aeena?oaoe?eia
aeine?aeaeaiiy aoei /anoeiith aea?aeathaeaeaoii? oaie IAe? a?ieia??
Oa?e?anueeiai aea?aeoi?aa?neoaoo “Eeioeiii oa iieaeoey?ii iaoaiicie
aaeaioaoei? iaoaaieicio i?e ieeniiio no?ani” (? Ae? 0197U008188).

Iaoa ? caaea/? aeine?aeaeaiiy. Iaoith ?iaioe aoei anoaiiaeaiiy
iniiaieo iaoai?ci?a ae?? ?ii?a Hg2+ ? Ni2+ ia aeoeai?noue (-AEE-neioace
a ia/?ioe? ? ?ie? aaiie?co oa ci?i ??aiy a?aeiiaeaiiai aeooao?iio (GSH)
a ?aae?caoe?? oeeo iaoai?ci?a. O ca’yceo c iaoith aeine?aeaeaiiy, a
oaeiae a?aoiaoth/e, ui ??aaiue a?aeiiaeaiiai aeooao?iio a cia/i?e i???
aecia/a?oueny aeoeai?noth aeooao?ii?aaeoeoace ? aaia?aoe??th IAAeOI
[Pinto R.E., Barley W., 1969], aoee iinoaaeai? oae? caaea/?:

Aea/eoe aieea HgCl2 oa CoCl2 ia aeoeai?noue (-AEE-neioace,
aeooao?ii?aaeoeoace, aetheici-6-oinoaoaeaaeae?iaaiace oa ai?no
a?aeiiaeaiiai aeooao?iio a ia/?ioe?, a oaeiae ia ai?no i?iaeoeo?a
aaiie?co ? aai-ca’ycoaaeueiiai a?eeo aaiiiaeneio a ne?iaaooe? e?ia?
uo??a.

Aea/eoe aieea HgCl2, aai?io oa ne?iaaoee e?ia? ?ioaeoieo ? aeine?aeieo
oaa?ei ia aeoeai?noue (-AEE-neioace ia/?ioe? a aeine?aeao in vitro.

A?aoiaoth/e aeai? uiaei aioeaaiie?oe/ii? ae?? (-aae?aiiaeieaoi?o
i?ii?aiieieo [Niieineee A.I. e ae?., 1988] oa aioeieneaeaioii? ae??
a?aeiiaeaiiai aeooao?iio [Meister A., Anderson M.E., 1983], aea/eoe
aieea noi?niiai aaaaeaiiy i?ii?aiieieo ? HgCl2 aai CoCl2, a oaeiae
noi?niiai aaaaeaiiy CoCl2 ? GSH, ia aeuaiaaaaeai? a?io?i?/i? iieacieee.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a. Aia?oa anoaiiaeaii, ui oei?eae
eiaaeueoo aeeeeea? iaeiie/aiiy a ne?iaaooe? e?ia? iiaeeo?eiaaieo
eiaaeueoii aaiii?ioa?i?a oa a?eueo ae?aaeaia ? o?eaaea, o ii??aiyii? c
oei?eaeii ?ooo?, aaeueioaaiiy aeoeaiino? (-AEE-neioace a ia/?ioe?.

Aia?oa anoaiiaeaii, ui cieaeaiiy aeoeaiino? (-AEE-neioace a ia/?ioe? ?
iaeiie/aiiy i?iaeoeo?a aaiie?co a ne?iaaooe? e?ia? a ia?o? aiaeeie ae??
HgCl2 oa CoCl2 caiia?aa?oueny i?e iiia?aaeiueiio aaaaeaii?,
a?aeiia?aeii, (-aae?aiiaeieaoi?o i?ii?aiieieo oa a?aeiiaeaiiai
aeooao?iio.

Iieacaii, ui ?iaeoeoth/a ae?y aea/aieo nieae iaoae?a ia (-AEE-neioacio
aeoeai?noue iiaea aooe iineaaeaia iiia?aaei?i aaaaeaiiyi i?ii?aiieieo
aai, ye anoaiiaeaii aeey oei?eaeo eiaaeueoo, aaaaeaiiyi a?aeiiaeaiiai
aeooao?iio.

Anoaiiaeaii, ui ci?ie ai?noo a?aeiiaeaiiai aeooao?iio a ia/?ioe? i?e
ae?? HgCl2 oa CoCl2 a iaai?e i??? caeaaeaoue a?ae iaeiie/aiiy i?iaeoeo?a
aaiie?co a ne?iaaooe? e?ia? ? caiia?aathoueny a oiiaao a?aenooiino?
aaiie?co.

Oai?aoe/ia oa i?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a. Caeiaoo? a
oe?e ?iaio? aeai? na?ae/aoue i?i caeaaei?noue aeeiai?ee aeoeaiino?
eeth/iaiai oa?iaioo a?ineioaco aaio a?ae iaeiie/aiiy i?iaeoeo?a
aaiie?co ? caeaoiino? ?ii?a iaoaeo oi?ioaaoe iaoaeiii?o??eiiaee
eiiieaen, ui cia/ii ?icoe?th? oyae uiaei ?aaoeyoe?? a?ineioaco aaio a
ia/?ioe? nnaaoe?a.

I?aeoe/ia cia/aiiy ia? anoaiiaeaiiy aaaeeeai? ?ie? aaiie?co a
iaoai?ciao ae?? ?ii?a aaaeeeo iaoae?a ia a?ineioac aaio a ia/?ioe?, a
oaeiae caeaoiino? (-aae?aiiaeieaoi?o i?ii?aiieieo oa a?aeiiaeaiiai
aeooao?iio caiia?aaoe aaiie?co a ia?o? aiaeeie ae??, a?aeiia?aeii, HgCl2
oa CoCl2. Caa??aaiiy aeoeaiino? (-AEE-neioace a ia/?ioe? ia
eiio?ieueiiio ??ai? a ia?o? aiaeeie ? ciaioaiiy aai caiia?aaiiy
iiaeaeueoi? ?iaeoeoe?? oa?iaioo i?ae aieeaii oeeo iaoae?a a oiiaao
a?aenooiino? aaiie?co iiaea aooe aeei?enoaii i?e ?ic?iaoe?
oa?aiaaoe/ieo caoiae?a uiaei e?eoaaiiy io?o?iue nieyie aaaeeeo iaoae?a
oa oiene/ieo ii?oe??e.

Iniaenoee aianie caeiaoaa/a. Aeena?oaoe?eia aeine?aeaeaiiy aeeiiaii
i?ae iaoeiaei ea??aieoeoaii aeieo. a?ie. iaoe I.A.Eae?iaia, a
ni?a?ia?oieoeoa? c eaiae. a?ie. iaoe ?.A.I?e?o/aiei, c yeeie aaoi? ia?
ni?euei? ioae?eaoe??. An? ?acoeueoaoe, ui i?eaaaeai? a ?oeiieno,
iaea?aeai? aaoi?ii naiino?eii. Aeena?oaioii iniaenoi i?iaaaeaii
aenia?eiaioe ? aecia/aiiy aea?aieo aeey aeine?aeaeaiiy a?io?i?/ieo
iieaciee?a, i?iaiae?ciaaia e?oa?aoo?a ca oaiith aeine?aeaeaiiy,
iaaiai?aii iaea?aeai? ?acoeueoaoe.

Ai?iaaoe?y ?acoeueoao?a aeena?oaoe??. Ca iaoa??aeaie aeena?oaoe??
c?iaeai? aeiiia?ae? ia i?aeia?iaeiiio neiiic?oi? “Aeieiae/aneea
iaoaieciu noa?aiey”, Oa?e?a, 1996 ? ., ia VII a?io?i?/iiio c’?cae?,
Ee?a, 1997 ?., ia i?aeia?iaei?e eiioa?aioe?? “Ooiaeaiaioaeueiua e
i?eeeaaeiua aniaeou nia?aiaiiie aeioeiee”, N.-Iaoa?ao?a, 1998 ?., ia
iaoeia?e eiioa?aioe?? iieiaeeo a/aieo-a?ieia?a OAeO, Oa?e?a 1996 ?.

Ioae?eaoe??. Ca iaoa??aeaie aeena?oaoe?? iioae?eiaaii 4 noaoo? oa 5 oac
aeiiia?aeae.

No?oeoo?a ? ianya ?iaioe. Aeena?oaoe?y neeaaea?oueny c? anooio, iaeyaeo
e?oa?aoo?e, iaoiaee/ii? /anoeie, o?ueio ?icae?e?a ?acoeueoao?a
aeine?aeaeaiue oa ?o iaaiai?aiiy, aeniiae?a ? ia?ae?eo e?oa?aoo?ieo
iineeaiue (260 aeaea?ae). ?iaioa aeeeaaeaia ia 136 noi?. ?acoeueoaoe
aeine?aeaeaiue ?ethno?iaaii 19 ?enoieaie oa 17 oaaeeoeyie.

INIIAIEE CI?NO ?IAIOE

O ia?oiio ?icae?eo ?iaioe iiaeaii iaeyae e?oa?aoo?e ca oaiith
aeena?oaoe??. Iniaeeaa oaaaa i?eae?eaia iniiaiei iaoai?ciai ?aaoeyoe??
(-ai?iieaaoe?iaoneioace a ia/?ioe? nnaaoe?a, a oiio /ene? ?ie? aaio,
aai-ca’ycoaaeueieo a?ee?a oa ai?iiiaeueieo oaeoi??a a ?aaoeyoe??
oa?iaioo, a oaeiae aieeao nieae aaaeeeo iaoae?a oa ci?i ??aith
a?aeiiaeaiiai aeooao?iio a ia/?ioe?. ?icaeyiooe a?ieia?/i? ooieoe?? GSH,
oa oaeoi?e, ui aieeaathoue ia eiai ai?no a ia/?ioe? nnaaoe?a.

O ae?oaiio ?icae?eo iienaii iaoa??aee oa iniiai? iaoiaee aeine?aeaeaiiy.

Iaoa??aee oa iaoiaee aeine?aeaeaiiy

A ?iaio? aeei?enoai? uo?e e?i?? A?noa? 3-o i?ny/iiai a?eo iaio noaoae.
Naiee ciaoiaeeeenue a oac? proestrus [Ee?oaiaeao ss.Ae., 1973].
CoCl2(6H2O oa HgCl2 aoei aaaaeaii a noaeaoaeuei?e aeic?,
a?aeiia?aeii, 3 ia [Maines M.D., 1977; Eaeeiai I.A., Aaeiaaoeeay E.A,
1986] oa 0,7 ia [Maines M.D., 1977] ia 100 a iane o?ea oaa?eie.
I?ii?aiieie (0,025% ?ic/ei) aoei aaaaeaii a aeic? 0,15 ia ia 100 a
iane o?ea [Bassukevitz Y. et al., 1989], a?aeiiaeaiee aeooao?ii (10%
?ic/ei) – a aeic? 50 ia ia 100 a iane o?ea [Eiiaae A.Ae. e ae?.,
1988]. An? niieoee aaaaeaii aioo??oiuei/a?aaeiii. I?e noi?niiio
aaaaeaii? i?ii?aiieie aoei aaaaeaii ca 30 oa aei aaaaeaiiy oei?eaeo
eiaaeueoo aai ?ooo?, a?aeiiaeaiee aeooao?ii – ca 15 oa aei aaaaeaiiy
CoCl2. Oaa?ei a?aee a aeine?ae i?ney aaaaeaiiy HgCl2 aai CoCl2 – /a?ac
30 oa, 2 aiae aai 24 aiae; i?ney aaaaeaiiy o?eueee i?ii?aiieieo – /a?ac
1 aiae, 2,5 aiae aai 24 aiae (eiio?ieue ia aeieaoi?); i?ney aaaaeaiiy
o?eueee a?aeiiaeaiiai aeooao?iio – /a?ac 15 oa, 45 oa oa 2 aiae
(eiio?ieue ia GSH). Ia’?eoii aeine?aeaeaiiy aoee ia/?iea oa e?ia
oaa?ei. A aeine?aeao in vitro aeei?enoaii ia/?ieo ?ioaeoieo
uo??a-naioe?a.

Ia/?ieo ia?oocoaaee oieiaeiei o?c?ieia?/iei ?ic/eiii in situ.
Iinoi?oioiiae??aeueio o?aeoe?th io?eioaaee aeeoa?aioe?aeueiei
oeaio?eooaoaaiiyi a 0,1 I E-Na-oinoaoiii aooa??, pH 7,5 [Auaiei I.Ae.,
1982].

Aecia/aiiy (-AEE-neioacii? aeoeaiino? i?iaaaeaii a aiiiaaiao? ia/?iee
ca iaoiaeii [Marver H.S. et al., 1966]. (-AEE, ui ooai?thaaeanue, aoei
ia?aaaaeaii aei oi?ie i??ieo eei’yo?iiyi a i?enooiino? aoeaoeeaoeaoiio
[Granick S., 1966]. I??ieueio oi?io (-AEE a?aeae?eyee a?ae
ai?iiaoeaoiio [Sassa S. et al., 1975] oa ?? ai?no aecia/aee i?ney
caaa?aethaaiiy ?aaeoeaii Y?e?oa. Ieoiio aeoeai?noue oa?iaioo ae?aaeaee
a iiieue (-AEE/ ia a?eeo ca 1 aiae.

Ai?no GSH aecia/aee a aiiiaaiao? ia/?iee niaeo?ioioiiao?e/ii ii
iiaeeiaiith eiiieaeno c aeeienaiii i?e 305 ii [Iooeeeia O.A., 1982] oa
ae?aaeaee a ieiieue/a ne?i? oeaieie. Aeoeai?noue aeooao?ii?aaeoeoacu
[*a?iia I.I., 1979] oa aetheici-6-oinoaoaeaaeae?iaaiace [Bottomley R.H.
et al., 1963] aecia/aee a iinoi?oioiiae??aeuei?e o?aeoe??
niaeo?ioioiiao?e/ii ii ci?i? iiaeeiaiiy IAAeOI (340 ii) i?e 37oC a
i?enooiino? a?aeiia?aeieo noano?ao?a. Aeoeai?noue oa?iaio?a ae?aaeaee a
iiieue IAAeOI/ia a?eeo ca 1 oa.

Niaeo? iiaeeiaiiy ne?iaaoee e?ia? ?a?no?oaaee ia aeaioi?iiaiaaiio
niaeo?ioioiiao?? Specord UV-VIZ i?e 37oC a 0,1 I Na-oinoaoiiio aooa??,
?I 7,1 [Hrkal Z., Muller-Eberhard U., 1971]. Ia i?aenoaa? ci?i
iioe/ii? aonoeie ne?iaaoee e?ia? a Soret-cii? (ciia iiaeeiaiiy
aaiii?ioa?i?a: 380-450 ii) oa i?e 280 ii ?iaeee aeniiaie i?i ai?no,
a?aeiia?aeii, aaio oa aaiii?ioa?i?a [Smith A., 1993; Yonetani T. et al.,
1974] (i?iaeoeoe aaiie?co), oa aaiiiaeneio [Takahashi N. et al., 1985].
Iioe/io aonoeio ?ic?aoiaoaaee ii ??cieoe? iaeneioio oa i?i?ioio
iiaeeiaiiy a a?aeiia?aei?e cii? [Perkampus H.-H., 1992] oa ae?aaeaee a
( A/ia a?eeo.

Ai?no a?eeo aecia/aee ca iaoiaeii Eio?? a iiaeeo?eaoe?? I?eea?a
[Miller G.L., 1959]. Noaoenoe/io ia?iaeo i?iaaaeaii ca iaoiaeii
Nouethaeaioa-O?oa?a.

O o?aoueiio, /aoaa?oiio oa i’yoiio ?icae?eao aeena?oaoe?? iaaaaeaii
iniiai? ?acoeueoaoe aeine?aeaeaiue oa ?o iaaiai?aiiy.

?acoeueoaoe aeine?aeaeaiue oa ?o iaaiai?aiiy

Aieea oei?eaeo ?ooo? oa oei?eaeo eiaaeueoo ia aeoeai?noue
(-ai?iieaaoe?iaoneioace oa ai?no a?aeiiaeaiiai aeooao?iio a ia/?ioe?
uo??a. Oei?eae ?ooo? oa oei?eae eiaaeueoo aeeeeeathoue aeaiooacio ci?io
(-AEE-neioacii? aeoeaiino? a ia/?ioe? uo??a iaio noaoae a ia?oo aeiao
i?ney aaaaeaiiy: cieaeaiiy a ia?o? aiaeeie c ianooiiei i?aeaeuaiiyi ia
24 aiaeeio (oaae.1,2).

Oaaeeoey 1

Aeoeai?noue (-AEE-neioace, aeooao?ii?aaeoeoace,
aetheici-6-oinoaoaeaaeae?iaaiace (Ae-6-OAeA) oa ai?no GSH a ia/?ioe? ?
iioe/ia aonoeia ne?iaaoee e?ia? uo??a-naioe?a a ??ci? no?iee i?ney
aaaaeaiiy HgCl2 aai CoCl2 (M±m, n=6-8)

*an i?ney ae??

Ae?y Eiio?ieue 30 oa 2 aiae 24 aiae

Aeoeai?noue (-AEE-neioace, iiieue AEE/ia a?eeo ca 1 aiae

HgCl2 0,098±0,003 0,067±0,006(p3) 0,096±0,007 0,168±0,009(p3)

CoCl2 0,085±0,007 0,025±0,004(p3) 0,036±0,004(p3) 0,141±0,010(p2)

Iioe/ia aonoeia ne?iaaoee e?ia? a Soret-cii?, (A/ia a?eeo

HgCl2 0,045±0,002 0,064±0,004(p2) – –

CoCl2 0,045±0,002 0,052±0,003(t) 0,060±0,002(p2) 0,036±0,002(p1)

Iioe/ia aonoeia ne?iaaoee e?ia? i?e 280 ii, (A/ia a?eeo

HgCl2 0,69±0,06 0,52±0,03(p1) – –

CoCl2 0,71±0,05 0,60±0,06 0,55±0,02(p1) 0,69±0,03

Ai?no a?aeiiaeaiiai aeooao?iio, ieiieue/a oeaieie

HgCl2 4,81±0,24 4,19±0,2(t) 3,47±0,14(p3) 5,34±0,23

CoCl2 4,41±0,22 3,64±0,3(t) 3,88±0,3 5,08±0,26(t)

Aeoeai?noue aeooao?ii?aaeoeoace, iiieue IAAeOI/ia a?eeo ca 1 oa

HgCl2 73,9±5,8 70,3±4,1 55,2±4,9(p1) 75,9±5,2

CoCl2 69,9±5,4 82,9±5,1 53,7±7,1(p1) 66,8±4,2

Aeoeai?noue Ae-6-OAeA, iiieue IAAeOI/ia a?eeo ca 1 oa

HgCl2 27,3±2,5 30,2±2,4 20,8±1,2(p1) 32,3±2,6

CoCl2 31,3±2,4 37,7±3,0 42,5±3,2(p1) 53,2±5,1(p2)

I?ei?oee: p1 – pOaaeeoey 2 Aeoeai?noue (-AEE-neioace, aeooao?ii?aaeoeoace, aetheici-6-oinoaoaeaaeae?iaaiace (Ae-6-OAeA) oa ai?no GSH a ia/?ioe? ? iioe/ia aonoeia ne?iaaoee e?ia? uo??a-naieoeue a ??ci? no?iee i?ney aaaaeaiiy HgCl2 aai CoCl2 (M±m, n=6-8) *an i?ney ae?? Ae?y Eiio?ieue 30 oa 2 aiae 24 aiae Aeoeai?noue (-AEE-neioace, iiieue AEE/ia a?eeo ca 1 aiae HgCl2 0,081±0,005 0,049±0,005(p2) 0,079±0,005 0,266±0,013(p3) CoCl2 0,084±0,005 0,038±0,005(p2) 0,033±0,004(p3) 0,196±0,016(p3) Iioe/ia aonoeia ne?iaaoee e?ia? a Soret-cii?, (A/ia a?eeo HgCl2 0,021±0,002 0,049±0,006(p2) – – CoCl2 0,021±0,002 0,060±0,006(p2) 0,039±0,004(p2) 0,022±0,002 Iioe/ia aonoeia ne?iaaoee e?ia? i?e 280 ii, (A/ia a?eeo HgCl2 0,76±0,03 0,54±0,02(p1) – – CoCl2 0,76±0,06 0,64±0,02(t) 0,52±0,02(p2) 0,61±0,03(p1) Ai?no a?aeiiaeaiiai aeooao?iio, ieiieue/a oeaieie HgCl2 4,10±0,22 3,26±0,3(t) 2,78±0,20(p2) 7,54±0,3(p3) CoCl2 4,11±0,16 5,07±0,33(t) 4,33±0,32 8,13±0,4(p3) Aeoeai?noue aeooao?ii?aaeoeoace, iiieue IAAeOI/ia a?eeo ca 1 oa HgCl2 61,3±4,4 62,7±6,7 68,5±3,7 67,0±5,1 CoCl2 54,5±4,7 61,1±3,6 66,8±5,5 70,8±3,8(p1) Aeoeai?noue Ae-6-OAeA, iiieue IAAeOI/ia a?eeo ca 1 oa HgCl2 43,3±3,9 49,5±4,8 68,5±3,7(p2) 77,0±3,9(p3) CoCl2 45,3±4,0 46,1±6,2 45,4±4,2 39,5±4,4 I?ei?oee: p1 – pOaaeeoey 3 Aeoeai?noue (-AEE-neioace a ia/?ioe? uo??a a aeine?aeao in vitro i?e ?ieoaaoe?? aiiiaaiaoo ia/?iee ?ioaeoieo uo??a-naioe?a a i?enooiino? HgCl2, aai?io, aai ne?iaaoee e?ia? (e?ioeaaa eiioeaio?aoe?y 10%) ?ioaeoieo ? aeine?aeieo uo??a (iiieue AEE/ia a?eeo ca 1 aiae, M±m, n=4-5) Oiiae ?ieoaaoe?? Aeoeai?noue Nooiaiue ?ia?aoaaiiy Eiio?ieue 0,096(0,006 0 35 ieI HgCl2 0.043(0.005(p1) 50% 50 ieI HgCl2 0 100% 50 ieI HgCl2 + 50 ieI Oeen 0,099(0,015 0 50 ieI HgCl2 + 100 ieI AeOO 0,105±0,007 0 0,1 ieI aai?i 0,041(0,006(p1) 53% 1 ieI aai?i 0 100% Ne?iaaoea I a 0,080(0,009 18% Ne?iaaoea II b 0,079(0,008 17% Ne?iaaoea III c 0,049(0,010(p1) 49% I?ei?oee: p1 - p Barannik O.V. The mechanisms of mercury chloride and cobalt chloride action on (-aminolevulinate synthase activity in rat liver.– Manuscript. Thesis for a scientific degree of candidate of biological sciences by speciality 03.00.04 – biochemistry.– Kharkov State University, Kharkov, 1999. The thesis is devoted to the investigation of the mechanisms of mercury or cobalt chloride action on the activity of the heme biosynthesis key enzyme, (-aminolevulinate synthase, in rat liver. The entering of the heavy metals to the human and animal organism leads to different functional and metabolic disorders, including the disorders of heme and hemoproteins biosynthesis. Toxic porphyrias development is mainly due to the breach of the regulation of (-aminolevulinate synthase ((-ALAS) activity. Heavy metals ions may act on the (-ALAS activity both straight and by the increasing of free heme content. The influence of the liver reduced glutathione (GSH) content alterations under metal action is also probable. So the possibility of the weakening of heavy metal action on the liver (-aminolevulinate synthase activity by prevention of the hemolysis and excessive heme and metal-porphyrin entering from the circulation to the liver cells and the influence of the liver reduced glutathione content alterations were studied. The dissertation consists on the introduction, the review of the literature on the chosen theme, the description of the main methods of the investigation, three parts of the experimental results with their discussion, conclusions and literature cited. The literature review is devoted to the regulation of the (-ALAS activity in rat liver, including the role of heme-binding proteins and heme transport from the circulation to the liver, and to the regulation of the reduced glutathione content and the role of the glutathione reductase and NADPH-generating dehydrogenase in the supporting of the cell pool of GSH. The experiments have revealed mercury chloride (0,7 mg per 100 g body weight) to cause 30% inhibition of the rat liver (-ALAS activity and hemolysis products accumulation in rat serum 30 min after injection. 2 hours after injection (-ALAS activity returns to control levels. Cobalt chloride (3 mg per 100 g body weight) caused cobalt-modificated hemoproteins accumulation in rat serum and more expressed and prolonged inhibition of the liver (-ALAS activity first hours after administration. Data obtained reveal the influence of the ability of metal ion to form metal-porphyrin complex and the hemolysis products accumulation in rat serum, but not of the liver reduced glutathione content on (-ALAS activity dynamics. No gender-linked features of the (-ALAS activity were found in intact rats. The direction of the rat liver (-ALAS activity alterations was independent on the animal gender. The hemolysis products content was less in the serum of intact females, than of males, and sharply increased in females 30 min after metal salt administration. 24 hours after metal salt injection the increase of the (-ALAS activity was observed, being more expressed in females. The reduced glutathione decrease was observed in rat liver 2 hours after HgCl2 administration and in males was found to be followed by the inhibition of glutathione reductase and glucose-6-phosphate dehydrogenase in the liver. Co-administration of HgCl2 and propranolol has prevented both the decrease of rat liver (-ALAS activity and hemolysis products accumulation in rat serum. GSH content didn’t fall first hours after HgCl2 administration if no hemolysis take place. CoCl2 and propranolol co-administration hasn’t alter the durability and the degree of (-ALAS activity inhibition, but has caused the accumulation of the hemolysis products in rat serum and liver GSH content decrease 30 min after the action. The induction of rat liver (-ALAS 24 hours after co-administration of metal salt and propranolol was less expressed than after the injection only metal salt. The propranolol injection (0,15 mg per 100 g body weight) was found to decrease both rat liver (-ALAS activity and hemolysis products content in rat serum. Co-administration cobalt chloride and reduced glutathione (50 mg per 100 g body weight) has prevented the inhibition of (-ALAS in the liver and modificated hemolysis products accumulation in rat serum. Only GSH injection was found to increase the rat liver reduced glutathione content (15 and 45 min after action) and the (-ALAS inhibition (45 min and 2 h 15 min after injection). The inhibition of the liver (-ALAS activity after propranolol and GSH treatment and the weakening of metal action on the (-ALAS activity in rat liver after co-administration of HgCl2 and (-adrenoblocator propranolol, having amphyphilic properties, or CoCl2 and water-soluble antioxydant GSH confirm the expediency of the propranolol and reduced glutathione application for the inherited and toxic porphyria treatment. The prevention of the liver (-aminolevulinate synthase inhibition and less or no further induction after HgCl2 and CoCl2 action under conditions of no hemolysis products accumulation testifies on the great role of hemolysis in the realisation of mercury and cobalt chloride action of the heme biosynthesis key enzyme in liver. Key words: heme, (-aminolevulinate synthase, reduced glutathione, mercury chloride, cobalt chloride, propranolol. I?aeienaii aei ae?oeo 16.12.98 ?. Oi?iao 60x84/16 Oi. ae?oe. a?e. 1,0. Oe?aae – 100 i?ei. Cai.23 *I «Iiaeai», Oa?e?a, i?.Eai?ia, 60 – I?ae noi?niei aaaaeaiiyi i?ii?aiieieo oa HgCl2 ?icoi??oueny aaaaeaiiy oei?eaeo ?ooo? /a?ac 30 oa i?ney ?i’?eoe?? i?ii?aiieieo; i?ae /anii i?ney noi?niiai aaaaeaiiy i?ii?aiieieo oa HgCl2 ?icoi??oueny /an, ui ieioea c iiiaioo aaaaeaiiy oei?eaeo ?ooo? – I?ae noi?niei aaaaeaiiyi i?ii?aiieieo oa NiCl2 ?icoi??oueny aaaaeaiiy oei?eaeo eiaaeueoo /a?ac 30 oa i?ney ?i’?eoe?? i?ii?aiieieo; i?ae /anii i?ney noi?niiai aaaaeaiiy i?ii?aiieieo oa NiCl2 ?icoi??oueny /an, ui ieioea c iiiaioo aaaaeaiiy oei?eaeo eiaaeueoo. I?ae noi?niei aaaaeaiiyi GSH oa NiCl2 ?icoi??oueny aaaaeaiiy oei?eaeo eiaaeueoo /a?ac 15 oa i?ney ?i’?eoe?? a?aeiiaeaiiai aeooao?iio; i?ae /anii i?ney noi?niiai aaaaeaiiy GSH oa NiCl2 ?icoi??oueny /an, ui ieioea c iiiaioo aaaaeaiiy oei?eaeo eiaaeueoo.

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