Coexposure of lead- and lipopolysaccharide-induced liver injury in rats: involvement of nitric oxide-initiated oxidative stress and TNF-alpha.
In this study, we investigated the interaction between lipopolysaccharide (LPS) and lead (Pb) and the involvement of tumor necrosis factor-alpha (TNF-alpha) and oxidative stress in Pb-plus-LPS (Pb/LPS)-induced liver damage in rats. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-alpha, nitric oxide (NO), and lipid peroxidation (LPO) were determined in rats treated with Pb and/or LPS. Pb ranging from 0 to 15 mg/kg dose dependently increased AST, ALT, NO, or LPO in LPS-treated rats. Pretreatment with iNOS inhibitor 1400W reduced NO, LPO, TNF-alpha, AST, and ALT in Pb/LPS-treated rats. Thus, Pb increased LPS-induced liver damage, which might be associated with increased NO-initiated oxidative stress and TNF-alpha in rats.
Liu
Ming-Yie
MY
Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan 704, Taiwan. myliu@mail.ncku.edu.tw
Cheng
Yu-Jung
YJ
Chen
Cheng-Kuang
CK
Yang
Bei-Chang
BC
D000410:Alanine Transaminase / Q000097:blood; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001596:Benzylamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007854:Lead / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000293:injuries*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D009942:Organometallic Compounds / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism*
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009573:Nitrites; D009942:Organometallic Compounds; D014409:Tumor Necrosis Factor-alpha; D007854:Lead; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C008261:lead acetate