Regulation of heme oxygenase activity in rat liver during oxidative stress induced by cobalt chloride and mercury chloride.

Activities of heme oxygenase and tryptophan-2,3-dioxygenase and cytochrome P450 content in liver as well as absorption of the Soret band and optical density at 280 nm in serum were determined 2 and 24 h after administration of HgCl(2) and CoCl(2) and after co-administration of the metal salts with alpha-tocopherol. Administration of HgCl(2) and CoCl(2) increased the contents of hemolysis products in the serum, induced heme oxygenase, and decreased cytochrome P450 content in the liver. Injection of HgCl(2) increased the activity of tryptophan-2,3-dioxygenase holoenzyme and enzyme saturation with the heme, but administration of CoCl(2) decreased these parameters. Pretreatment with alpha-tocopherol completely blocked the changes induced by HgCl(2) after 24 h. Induction of heme oxygenase induced by CoCl(2) was not blocked by alpha-tocopherol, but this antioxidant normalized the increase in the level of hemolysis products in the serum and decrease in tryptophan-2,3-dioxygenase holoenzyme activity and cytochrome P450 content. Mechanisms of regulation of heme oxygenase by mercury and cobalt ions are discussed.

[Metabolism of heme and hemoproteins in rat liver upon administration of mercuric chloride]. / Metabolizm gema i gemoproteinov v pecheni krys pri vvedenii khlorida rtuti.

Rat liver delta-aminolevulinate synthase (delta-ALAS) activity in the early period after mercury chloride administration (0.7 mg per 100 g body weight) was found to be followed by free heme level increase, which was registered by the increase of heme saturation of the heme-binding protein tryptophan-2,3-dioxygenase (T-2,3-DO). delta-ALAS and heme oxygenase activity increase was observed 24 h after action. Microsomal cytochromes P450 and b5 levels decrease. Heme saturation of the T-2,3-DO returned to control level. Heme oxygenase and T-2,3-DO induction promoted hepatocytes free heme level normalization. Heme oxygenase and delta-ALAS induction role in the liver cells defense from the oxidative damage is discussed.