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Melatonin attenuates lipopolysaccharide‐induced down‐regulation of pregnane X receptor and its target gene CYP3A in mouse liver
Author(s) -
Xu DeXiang,
Wei Wei,
Sun MeiFang,
Wei LingZhen,
Wang JianPing
Publication year - 2005
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2004.00171.x
Subject(s) - pregnane x receptor , melatonin , cyp3a , medicine , endocrinology , biology , glutathione , superoxide dismutase , lipopolysaccharide , glutathione peroxidase , glutathione reductase , nuclear receptor , oxidative stress , cytochrome p450 , transcription factor , biochemistry , gene , enzyme , metabolism
Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily that regulates target gene transcription in a ligand‐dependent manner. Our earlier study indicated that reactive oxygen species contribute to lipopolysaccharide (LPS)‐induced down‐regulation of PXR and its target gene CYP3A in mouse liver. Melatonin is a powerful endogenous antioxidants. In this study, we investigated the effects of melatonin on LPS‐induced down‐regulation of PXR and CYP3A in mouse liver. Mice were intraperitoneally administrated different doses of melatonin before and/or after LPS treatment. PXR and CYP3A11 mRNA levels were measured using RT‐PCR. Erythromycin N ‐demethylase (ERND) was used as an indicator of CYP3A catalytic activity. Results indicated that melatonin significantly attenuated LPS‐induced down‐regulation of PXR and CYP3A11 mRNA levels in a dose‐dependent manner. Repeated doses of melatonin (10 mg/kg) treatments also significantly attenuated LPS‐induced down‐regulation of dexamethasone‐inducible CYP3A11 mRNA level and ERND activity in mouse liver. In addition, the present study also shows that melatonin significantly increased hepatic superoxide dismutase, Se‐dependent glutathione peroxidase, glutathione reductase and catalase activities and glutathione levels in LPS‐treated mice. These findings suggest that melatonin may exert its protective effects on LPS‐induced down‐regulation of PXR and CYP3A via counteracting LPS‐induced oxidative stress in mouse liver.