A Comparative Study of Gene Expression Profiles in Rat Liver After Administration of Alpha-Hexachlorocyclohexane and Lindane

Sumida, Kayo; Saito, Koichi; Oeda, Kenji; Yakabe, Yoshikuni; Otsuka, Masanori; Matsumoto, Hiroshi; Sekijima, Masaru; Nakayama, Koji; Kawano, Yukiko; Shirai, Tomoyuki

doi:10.2131/jts.32.261

Cited by 5 publications

(1 citation statement)

References 44 publications

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“…Acute lindane intoxication causes altered gene expression in rat liver. [56] There are reports that certain exogenous antioxidants strengthen the cellular xenobiotic metabolizing system, thereby protecting cells from oxidative stress. [7] In search for these new chemical entities as modulators of xenobiotic metabolism, we reviewed literature on Ayurvedic medicinal plants.…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective effect of curcumin on lindane-induced oxidative stress in male wistar rats

Singh

Sharma

2011

Toxicol Int

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Lindane, an organochlorine pesticide, is recognized as a major public health concern because of its potential toxic effects on human health. Its persistence in the body fluids may lead to continuous blood circulation, liver exposure and hepatotoxicity. The present study was undertaken to evaluate the possible protective role of curcumin on lindane-induced hepatotoxicity. Forty-two healthy adult male Wistar rats were divided into seven groups of six rats each. Group I was given dimethylsulfoxide. A single dose of lindane (60 mg/kg bw) was given to group II. Lindane (30 mg/kg bw) was given daily to group III for 14 days. Treatment with curcumin (100 and 200 mg/kg) was given to groups IV and V before (pretreatment) and to groups VI and VII after (post-treatment) 14 days exposure of lindane. Oxidative stress parameters and antioxidative enzymes were investigated in the liver of exposed and treated rats. A significant increase in lipid peroxidation, and decrease in glutathione level, Superoxide dismutase catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase and NADPH quinine reductase activities was observed in liver of rats exposed to lindane. Curcumin (Pre- and post-treatment) nearly normalized all these parameters. Histological alterations were also observed in the liver tissue after lindane exposure. Treatment with curcumin significantly prevented the lindane-induced histological alterations. In conclusion, curcumin has protective effect over lindane-induced oxidative damage in rat liver.

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Section: Introductionmentioning

confidence: 99%

Hepatoprotective effect of curcumin on lindane-induced oxidative stress in male wistar rats

Singh

Sharma

2011

Toxicol Int

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Toxicogenomics: transcription profiling for toxicology assessment

Zhou

Chou

Watkins

2009

Experientia Supplementum

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Carcinogenicity and mode of action evaluation for alpha-hexachlorocyclohexane: Implications for human health risk assessment

Bradley

Shoenfelt

Durda

2016

Regulatory Toxicology and Pharmacology

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Alpha-hexachlorocyclohexane (alpha-HCH) is one of eight structural isomers that have been used worldwide as insecticides. Although no longer produced or used agriculturally in the United States, exposure to HCH isomers is of continuing concern due to legacy usage and persistence in the environment. The U.S. Environmental Protection Agency (EPA) classifies alpha-HCH as a probable human carcinogen and provides a slope factor of 6.3 (mg/kg-day)(-1) for the compound, based on hepatic nodules and hepatocellular carcinomas observed in male mice and derived using a default linear approach for modeling carcinogens. EPA's evaluation, last updated in 1993, does not consider more recently available guidance that allows for the incorporation of mode of action (MOA) for determining a compound's dose-response. Contrary to the linear approach assumed by EPA, the available data indicate that alpha-HCH exhibits carcinogenicity via an MOA that yields a nonlinear, threshold dose-response. In our analysis, we conducted an MOA evaluation and dose-response analysis for alpha-HCH-induced liver carcinogenesis. We concluded that alpha-HCH causes liver tumors in rats and mice through an MOA involving increased promotion of cell growth, or mitogenesis. Based on these findings, we developed a threshold, cancer-based, reference dose (RfD) for alpha-HCH.

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A Comparative Study of Gene Expression Profiles in Rat Liver After Administration of Alpha-Hexachlorocyclohexane and Lindane

Cited by 5 publications

References 44 publications

Hepatoprotective effect of curcumin on lindane-induced oxidative stress in male wistar rats

Hepatoprotective effect of curcumin on lindane-induced oxidative stress in male wistar rats

Toxicogenomics: transcription profiling for toxicology assessment

Carcinogenicity and mode of action evaluation for alpha-hexachlorocyclohexane: Implications for human health risk assessment

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