EFFECTS OF LITHIUM-CHLORIDE ON HEME METABOLISM AND METALLOTHIONEIN CONTENT IN THE LIVER AND BRAIN OF RATS

The effects of lithium chloride (LiCl) on the contents of metallothionein and metals (lithium and zinc) and on the activities of key enzymes in heme metabolic pathways were investigated in the liver and brain of male Wistar rats. Animals were given a single i.p. injection of LiCl at a dose of 100 or 200 mg/kg. Control rats were treated with isoequivalent doses of NaCl. Serum lithium (Li) concentration was revealed a significant enhancement at 3 h after a single LiCl (200 mg/kg, i.p.) administration. Li concentration in the hepatic cytosol was also found peak level at 3 h after LiCl administration, but Li in the brain cytosol reached to peak level at 6 h. Hepatic heme oxygenase activity reached to peak value at 6 h after a single injection of LiCl (200 mg/kg) to rats and subsequently restored to normal level in 24 h. delta-aminolevulinic acid synthetase activity decreased at 6 h after LiCl (200 mg/kg) administration. Contents of cytochrome P-450 and b5 and microsomal total heme were not affected significantly under this experimental condition. Metallothionein content in the hepatic cytosol was markedly increased at 12 h after LiCl (200 mg/kg) administration, and this increase was still noted 24 h after the treatment. These induced effects by LiCl on the heme oxygenase and metallothionein appear to be due to the action as a metal of Li salt rather than its pharmacological action.