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Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism.

Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism. Research Abstract Details 

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  • Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism. Abstract Text:

    cheng fangCheng Fang,melissa behrMelissa Behr,fang xieFang Xie,shijun luShijun Lu,meghan doretMeghan Doret,hongxiu luoHongxiu Luo,weizhu yangWeizhu Yang,kenneth aldousKenneth Aldous,xinxin dingXinxin Ding,jun guJun Gu,

    Chloroform causes hepatic and renal toxicity in a number of species. In vitro studies have indicated that chloroform can be metabolized by P450 enzymes in the kidney to nephrotoxic intermediate, although direct in vivo evidence for the role of renal P450 in the nephrotoxicity has not been reported. This study was to determine whether chloroform renal toxicity persists in a mouse model with a liver-specific deletion of the P450 reductase (Cpr) gene (liver-Cpr-null). Chloroform-induced renal toxicity and chloroform tissue levels were compared between the liver-Cpr-null and wild-type mice at 24 h following differing doses of chloroform. At a chloroform dose of 150 mg/kg, the levels of blood urea nitrogen (BUN) were five times higher in the exposed group than in the vehicle-treated one for the liver-Cpr-null mice, but they were only slightly higher in the exposed group than in the vehicle-treated group for the wild-type mice. Severe lesions were found in the kidney of the liver-Cpr-null mice, while only mild lesions were found in the wild-type mice. At a chloroform dose of 300 mg/kg, severe kidney lesions were observed in both strains, yet the BUN levels were still higher in the liver-Cpr-null than in the wild-type mice. Higher chloroform levels were found in the tissues of the liver-Cpr-null mice. These findings indicated that loss of hepatic P450-dependent chloroform metabolism does not protect against chloroform-induced renal toxicity, suggesting that renal P450 enzymes play an essential role in chloroform renal toxicity.

    Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism. Publishing Authors By Initials

    c fangC Fang,m behrM Behr,f xieF Xie,s luS Lu,m doretM Doret,h luoH Luo,w yangW Yang,k aldousK Aldous,x dingX Ding,j guJ Gu,

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    Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Toxicology and applied pharmacology

    VOLUME: 227

    Page Numbers: 48-55

    Journal Abbreviation: Toxicol. Appl. Pharmacol.

    ISSN: 0041-008X

    DAY: 23

    MONTH: 10

    YEAR: 2007

    Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism. Information

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    LANGUAGE: eng

    NlmUniqueID: 416575

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    Grant and Affiliation Information for Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism.

    AFFILIATION: Wadsworth Center, New York State Department of Health, Empire State Plaza, Box 509, Albany, NY 12201-0509, USA; School of Public Health, State University of New York at Albany, NY 12201, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Toxicol Appl Pharmacol

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