title: N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents.
abstract: Potent aryl hydrocarbon receptor agonists like PCB 126 (3,3',4,4',5-pentachlorobiphenyl) cause oxidative stress and liver pathology, including fatty liver. Our question was whether dietary supplementation with N-acetylcysteine (NAC), an antioxidant, can prevent these adverse changes. Male Sprague-Dawley rats were fed a standard AIN-93G diet (sufficient in cysteine) or a modified diet supplemented with 1.0% NAC. After one week, rats on each diet were exposed to 0, 1, or 5μmol/kg body weight PCB 126 by i.p. injection (6 rats per group) and euthanized two weeks later. PCB-treatment caused a dose-dependent reduction in growth, feed consumption, relative thymus weight, total glutathione and glutathione disulfide (GSSG), while relative liver weight, glutathione transferase activity and hepatic lipid content were dose-dependently increased with PCB dose. Histologic examination of liver tissue showed PCB 126-induced hepatocellular steatosis with dose dependent increase in lipid deposition and distribution. Dietary NAC resulted in a reduction in hepatocellular lipid in both PCB groups. This effect was confirmed by gravimetric analysis of extracted lipids. Expression of CD36, a scavenger receptor involved in regulating hepatic fatty acid uptake, was reduced with high dose PCB treatment but unaltered in PCB-treated rats on NAC-supplemented diet. These results demonstrate that NAC has a protective effect against hepatic lipid accumulation in rats exposed to PCB 126. The mechanism of this protective effect appears to be independent of NAC as a source of cysteine/precursor of glutathione.
authors: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, IA, United States.
authors: Ian K
authors: IK
authors: Lai
authors: Kiran
authors: K
authors: Dhakal
authors: Gopi S
authors: GS
authors: Gadupudi
authors: Miao
authors: M
authors: Li
authors: Gabriele
authors: G
authors: Ludewig
authors: Larry W
authors: LW
authors: Robertson
authors: Alicia K
authors: AK
authors: Olivier
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018955:CD36 Antigens / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D012720:Severity of Illness Index
chemical_list: D000975:Antioxidants; D018955:CD36 Antigens; D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls; D005978:Glutathione; C023035:3,4,5,3',4'-pentachlorobiphenyl; D000111:Acetylcysteine