Influence of Changes in Glutathione Concentration on Body Temperature and Tolerance to Cerebral Ischemia

L. S. Kolesnichenko^1*, V. I. Kulinsky¹, G. V. Sotnikova², and V. Yu. Kovtun³

¹Department of Bioorganic and Bioinorganic Chemistry and Department of Biochemistry, Irkutsk State Medical University, ul. Krasnogo Vosstaniya 1, Irkutsk 664003, Russia; fax: (395) 224-0826; E-mail: kulinsky@pp.irkutsk.ru

²Department of Physico-Chemical Biology, Irkutsk State University, ul. K. Marksa 1, Irkutsk 664000, Russia; fax: (395) 241-1855; E-mail: gaika@mail.ru

³SPC Pharmprotection, Vashutinskoe Shosse 11, Khimki 141400, Moscow Region, Russia; fax: (095) 572-4600; E-mail: pharmg@cityline.ru

^* To whom correspondence should be addressed.

Received March 28, 2002

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Two compounds that deplete glutathione (buthionine sulfoximine and diethyl maleate) with different mechanisms of action decrease body temperature and increase tolerance to complete global cerebral ischemia, both correlating closely with the glutathione concentration decrease. Glutathione apparently participates in the regulations of these functional parameters. GSH diethyl ester does not influence the latter, though it increases moderately the GSH concentration. Injection of GSH ester into the cerebral ventricles or subcutaneously selectively increases the GSH level in the brain and liver. An influence of the brain on the glutathione system in the liver was revealed. Diethyl maleate and GSH ester increase the activity of glutathione metabolizing enzymes under certain conditions.

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KEY WORDS: glutathione system, compounds depleting GSH, GSH ester, body temperature, cerebral ischemia

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