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N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents

Lai, Ian K., Dhakal, Kiran, Gadupudi, Gopi S., Li, Miao, Ludewig, Gabriele, Robertson, Larry W., Olivier, Alicia K.
Toxicology 2012 v.302 no.1 pp. 25-33
acetylcysteine, agonists, antioxidants, body weight, cysteine, dietary supplements, dose response, fatty acids, fatty liver, feed intake, glutathione, glutathione transferase, growth retardation, lipid content, liver, oxidative stress, polychlorinated biphenyls, protective effect, rats, toxicology
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.