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Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/ob mice.
Hepatology. 2007 Jun; 45(6):1355-65.Hep

Abstract

Cytochrome P450 2E1 (CYP2E1) activates several hepatotoxins and contributes to alcoholic liver damage. Obesity is a growing health problem in the United States. The aim of the present study was to evaluate whether acetone- or pyrazole-mediated induction of CYP2E1 can potentiate liver injury in obesity. CYP2E1 protein and activity were elevated in acetone- or pyrazole-treated obese and lean mice. Acetone or pyrazole induced distinct histological changes in liver and significantly higher aminotransferase enzymes in obese mice compared to obese controls or acetone- or pyrazole-treated lean mice. Higher caspase-3 activity and numerous apoptotic hepatocytes were observed in the acetone- or pyrazole-treated obese mice. Increased protein carbonyls, malondialdehyde, 4-hydroxynonenal-protein adducts, elevated levels of inducible nitric oxide synthase, and higher 3-nitrotyrosine protein adducts were found in livers of acetone- or pyrazole-treated obese animals, suggesting elevated oxidative and nitrosative stress. Liver tumor necrosis factor alpha levels were higher in pyrazole-treated animals. The CYP2E1 inhibitor chlormethiazole and iNOS inhibitor N-(3-(aminomethyl)-benzyl) acetamidine abrogated the toxicity and the oxidative/nitrosative stress elicited by the induction of CYP2E1.

CONCLUSION

These results show that obesity contributes to oxidative stress and liver injury and that induction of CYP2E1 enhances these effects.

Authors+Show Affiliations

Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17538970

Citation

Dey, Aparajita, and Arthur I. Cederbaum. "Induction of Cytochrome P450 2E1 [corrected] Promotes Liver Injury in Ob/ob Mice." Hepatology (Baltimore, Md.), vol. 45, no. 6, 2007, pp. 1355-65.
Dey A, Cederbaum AI. Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/ob mice. Hepatology. 2007;45(6):1355-65.
Dey, A., & Cederbaum, A. I. (2007). Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/ob mice. Hepatology (Baltimore, Md.), 45(6), 1355-65.
Dey A, Cederbaum AI. Induction of Cytochrome P450 2E1 [corrected] Promotes Liver Injury in Ob/ob Mice. Hepatology. 2007;45(6):1355-65. PubMed PMID: 17538970.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/ob mice. AU - Dey,Aparajita, AU - Cederbaum,Arthur I, PY - 2007/6/1/pubmed PY - 2007/7/13/medline PY - 2007/6/1/entrez SP - 1355 EP - 65 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 45 IS - 6 N2 - UNLABELLED: Cytochrome P450 2E1 (CYP2E1) activates several hepatotoxins and contributes to alcoholic liver damage. Obesity is a growing health problem in the United States. The aim of the present study was to evaluate whether acetone- or pyrazole-mediated induction of CYP2E1 can potentiate liver injury in obesity. CYP2E1 protein and activity were elevated in acetone- or pyrazole-treated obese and lean mice. Acetone or pyrazole induced distinct histological changes in liver and significantly higher aminotransferase enzymes in obese mice compared to obese controls or acetone- or pyrazole-treated lean mice. Higher caspase-3 activity and numerous apoptotic hepatocytes were observed in the acetone- or pyrazole-treated obese mice. Increased protein carbonyls, malondialdehyde, 4-hydroxynonenal-protein adducts, elevated levels of inducible nitric oxide synthase, and higher 3-nitrotyrosine protein adducts were found in livers of acetone- or pyrazole-treated obese animals, suggesting elevated oxidative and nitrosative stress. Liver tumor necrosis factor alpha levels were higher in pyrazole-treated animals. The CYP2E1 inhibitor chlormethiazole and iNOS inhibitor N-(3-(aminomethyl)-benzyl) acetamidine abrogated the toxicity and the oxidative/nitrosative stress elicited by the induction of CYP2E1. CONCLUSION: These results show that obesity contributes to oxidative stress and liver injury and that induction of CYP2E1 enhances these effects. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/17538970/Induction_of_cytochrome_P450_2E1_[corrected]_promotes_liver_injury_in_ob/ob_mice_ L2 - https://doi.org/10.1002/hep.21603 DB - PRIME DP - Unbound Medicine ER -