Adaptive tolerance in mice upon subchronic exposure to chloroform: Increased exhalation and target tissue regeneration

Toxicology and Applied Pharmacology
Sathanandam S AnandHarihara M Mehendale

Abstract

The aims of the present study were to characterize the subchronic toxicity of chloroform by measuring tissue injury, repair, and distribution of chloroform and to assess the reasons for the development of tolerance to subchronic chloroform toxicity. Male Swiss Webster (SW) mice were given three dose levels of chloroform (150, 225, and 300 mg/kg/day) by gavage in aqueous vehicle for 30 days. Liver and kidney injury were measured by plasma ALT and BUN, respectively, and by histopathology. Tissue regeneration was assessed by (3)H-thymidine incorporation into hepato- and nephro-nuclear DNA and by proliferating cell nuclear antigen staining. In addition, GSH and CYP2E1 in liver and kidney were assessed at selected time points. The levels of chloroform were measured in blood, liver, and kidney during the dosing regimen (1, 7, 14, and 30 days). Kidney injury was evident after 1 day with all three doses and sustained until 7 days followed by complete recovery. Mild to moderate liver injury was observed from 1 to 14 days with all three dose levels followed by gradual decrease. Significantly higher regenerative response was evident in liver and kidney at 7 days, but the response was robust in kidney, preventing progression of injury beyo...Continue Reading

References

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Citations

Aug 20, 2009·Critical Reviews in Food Science and Nutrition·Alan R BoobisStephen S Olin
Oct 18, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·K M SutherlandL S Van Winkle
Feb 3, 2007·Toxicology·Binu K PhilipHarihara M Mehendale
May 1, 2007·Current Protocols in Toxicology·Sachin S DeviHarihara M Mehendale

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