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

Author:
Lai, Ian K., Dhakal, Kiran, Gadupudi, Gopi S., Li, Miao, Ludewig, Gabriele, Robertson, Larry W., Olivier, Alicia K.
Source:
Toxicology 2012 v.302 no.1 pp. 25-33
ISSN:
0300-483X
Subject:
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
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.
Agid:
1103836