Prophylactic effect of melatonin on lead-induced inhibition of heme biosynthesis and deterioration of antioxidant systems in male rats.
We studied the protective role of the pineal hormone melatonin on lead-induced suppression of the heme synthesis pathway as a consequence of reduced antioxidant systems in rat. We injected rats intramuscularly with lead acetate (10 mg/kg body weight) daily for 7 days, which significantly abolished heme synthesis as evidenced by decreased blood hemoglobin, liver delta-aminolevulinic acid synthetase, erythrocytic delta-aminolevulinic acid dehydratase, and hepatic iron content. These effects were accompanied with marked elevation of hepatic lipid peroxidation and decreased enzymatic antioxidants such as glutathione reductase, glutathione-S-transferase, superoxide dismutase, and catalase, as well as nonenzymatic antioxidants such as total sulfhydryl groups and glutathione. Furthermore, lead treatment caused hepatic deficiency in copper and zinc accompanied by a significant elevation of lead concentration in both plasma and liver. Daily pretreatment with melatonin (30 mg/kg body weight) intragastrically prevented the suppressive effects of lead on heme-synthesizing enzymes and iron deficiency. In addition, preadministration of melatonin reduced the inhibitory effect of lead on both enzymatic and nonenzymatic antioxidants. This was accompanied by marked normalization of lipid peroxidation and modulation of copper and zinc levels in liver. The action of melatonin on lead-induced changes was attributed to protection of the antioxidant capacity in cells in addition to the ability of melatonin to scavenge free radicals.
El-Missiry
M A
MA
Department of Zoology, Faculty of Science, Mansoura University, Egypt. sinfac@mum.mans.eun.eg
D000624:5-Aminolevulinate Synthetase / Q000037:antagonists & inhibitors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism; D006418:Heme / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D007854:Lead / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000097:blood; D051381:Rats
D000975:Antioxidants; D007854:Lead; D006418:Heme; D000624:5-Aminolevulinate Synthetase; D000623:Porphobilinogen Synthase; D005978:Glutathione; D008550:Melatonin