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S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury.
Am J Physiol Gastrointest Liver Physiol. 2007 Jul; 293(1):G91-103.AJ

Abstract

Pyrazole treatment to induce cytochrome P-450 2E1 (CYP2E1) was recently shown to cause liver injury in ob/ob mice but not in lean mice. The present study investigated the effects of S-adenosyl-l-methionine (SAM) on the CYP2E1-dependent liver injury in ob/ob mice. Pyrazole treatment of ob/ob mice for 2 days caused necrosis, steatosis, and elevated serum transaminase and triglyceride levels compared with saline ob/ob mice. Administration of SAM (50 mg/kg body wt ip every 12 h for 3 days) prevented the observed pathological changes as well as the increase of apoptotic hepatocytes, caspase 3 activity, and serum TNF-alpha levels. SAM administration inhibited CYP2E1 activity but not CYP2E1 content. The pyrazole treatment increased lipid peroxidation, 4-hydroxynonenal and 3-nitrotyrosine protein adducts, and protein carbonyls. These increases in oxidative and nitrosative stress were prevented by SAM. Treatment of ob/ob mice with pyrazole lowered the endogenous SAM levels, and these were elevated after SAM administration. Mitochondrial GSH levels were very low after pyrazole treatment of the ob/ob mice; this was associated with elevated levels of malondialdehyde and 4-hydroxynonenal and 3-nitrotyrosine protein adducts in the mitochondria. All these changes were prevented with SAM administration. SAM protected against pyrazole-induced increase in serum transaminases, necrosis, triglyceride levels, caspase-3 activity, and lipid peroxidation even when administered 1 day after pyrazole treatment. In the absence of pyrazole, SAM lowered the slightly elevated serum transaminases, triglyceride levels, caspase-3 activity, and lipid peroxidation in obese mice. In conclusion, SAM protects against and can also reverse or correct CYP2E1-induced liver damage in ob/ob mice.

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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17446309

Citation

Dey, Aparajita, et al. "S-adenosyl Methionine Protects Ob/ob Mice From CYP2E1-mediated Liver Injury." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 293, no. 1, 2007, pp. G91-103.
Dey A, Caro AA, Cederbaum AI. S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G91-103.
Dey, A., Caro, A. A., & Cederbaum, A. I. (2007). S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. American Journal of Physiology. Gastrointestinal and Liver Physiology, 293(1), G91-103.
Dey A, Caro AA, Cederbaum AI. S-adenosyl Methionine Protects Ob/ob Mice From CYP2E1-mediated Liver Injury. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G91-103. PubMed PMID: 17446309.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. AU - Dey,Aparajita, AU - Caro,Andres A, AU - Cederbaum,Arthur I, Y1 - 2007/04/19/ PY - 2007/4/21/pubmed PY - 2007/9/13/medline PY - 2007/4/21/entrez SP - G91 EP - 103 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 293 IS - 1 N2 - Pyrazole treatment to induce cytochrome P-450 2E1 (CYP2E1) was recently shown to cause liver injury in ob/ob mice but not in lean mice. The present study investigated the effects of S-adenosyl-l-methionine (SAM) on the CYP2E1-dependent liver injury in ob/ob mice. Pyrazole treatment of ob/ob mice for 2 days caused necrosis, steatosis, and elevated serum transaminase and triglyceride levels compared with saline ob/ob mice. Administration of SAM (50 mg/kg body wt ip every 12 h for 3 days) prevented the observed pathological changes as well as the increase of apoptotic hepatocytes, caspase 3 activity, and serum TNF-alpha levels. SAM administration inhibited CYP2E1 activity but not CYP2E1 content. The pyrazole treatment increased lipid peroxidation, 4-hydroxynonenal and 3-nitrotyrosine protein adducts, and protein carbonyls. These increases in oxidative and nitrosative stress were prevented by SAM. Treatment of ob/ob mice with pyrazole lowered the endogenous SAM levels, and these were elevated after SAM administration. Mitochondrial GSH levels were very low after pyrazole treatment of the ob/ob mice; this was associated with elevated levels of malondialdehyde and 4-hydroxynonenal and 3-nitrotyrosine protein adducts in the mitochondria. All these changes were prevented with SAM administration. SAM protected against pyrazole-induced increase in serum transaminases, necrosis, triglyceride levels, caspase-3 activity, and lipid peroxidation even when administered 1 day after pyrazole treatment. In the absence of pyrazole, SAM lowered the slightly elevated serum transaminases, triglyceride levels, caspase-3 activity, and lipid peroxidation in obese mice. In conclusion, SAM protects against and can also reverse or correct CYP2E1-induced liver damage in ob/ob mice. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/17446309/S_adenosyl_methionine_protects_ob/ob_mice_from_CYP2E1_mediated_liver_injury_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00004.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -