title: Decrease in hepatotoxicity by lead exposure is not explained by its mitogenic response.
abstract: The present research was conducted to evaluate the effect of mitogen pre-exposure on CCl4-induced hepatotoxicity. Male Wistar rats were administered a single i.p. injection of CCl4 (0.3 ml kg-1 in corn oil) 48 h following either a single dose of lead nitrate (0.33 mg kg-1) or distilled water via i.v. injection. Hepatotoxicity, as measured by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was monitored 6, 24, 48, 72 and 120 h after CCl4 exposure. The lead nitrate-pretreated rats displayed markedly lower serum ALT and AST levels at 24, 48 and 72 h than rats pretreated with distilled water. However, treatment with the antimitotic agent colchicine did not alter the lead-induced protection. These findings suggest that the lead-induced protection is not associated with the major mitogenic response of lead, despite its strong temporal association. A critical review of the available toxicological data also argues against the lead protection being a function of its capacity to inhibit cytochrome P-450.
authors.affiliation: School of Public Health, N344 Morrill Science Center, University of Massachusetts, Amherst 01003, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Calabrese
authors.forename: L A
authors.initials: LA
authors.lastname: Baldwin
authors.forename: D A
authors.initials: DA
authors.lastname: Leonard
authors.forename: X Q
authors.initials: XQ
authors.lastname: Zhao
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D003078:Colchicine / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007275:Injections, Intravenous; D007854:Lead / Q000494:pharmacology*; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009566:Nitrates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008934:Mitogens; D009566:Nitrates; D007854:Lead; C017461:lead nitrate; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003078:Colchicine