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

Ian K Lai; Kiran Dhakal; Gopi S Gadupudi; Miao Li; Gabriele Ludewig; Larry W Robertson; Alicia K Olivier

doi:10.1016/j.tox.2012.07.007

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

Journal article

Peer reviewed

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

Ian K Lai, Kiran Dhakal, Gopi S Gadupudi, Miao Li, Gabriele Ludewig, Larry W Robertson and Alicia K Olivier

Toxicology (Amsterdam), Vol.302(1), pp.25-33

12/08/2012

DOI: 10.1016/j.tox.2012.07.007

PMCID: PMC3438370

PMID: 22824115

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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.

Antioxidants

Oxidative Stress

Toxicology

acetylcysteine

agonists

body weight

cysteine

dietary supplements

dose response

fatty acids

fatty liver

feed intake

glutathione

glutathione transferase

growth retardation

lipid content

liver

polychlorinated biphenyls

protective effect

rats

Details

Title: Subtitle: N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents
Creators: Ian K Lai
Kiran Dhakal
Gopi S Gadupudi
Miao Li
Gabriele Ludewig
Larry W Robertson
Alicia K Olivier
Resource Type: Journal article
Publication Details: Toxicology (Amsterdam), Vol.302(1), pp.25-33
Publisher: Elsevier Ireland Ltd
DOI: 10.1016/j.tox.2012.07.007
PMID: 22824115
PMCID: PMC3438370
ISSN: 0300-483X
eISSN: 1879-3185
Language: English
Date published: 12/08/2012
Academic Unit: Occupational and Environmental Health; Iowa Superfund Research Program
Record Identifier: 9984214689302771

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