title: Dimerumic acid protected oxidative stress-induced cytotoxicity in isolated rat hepatocytes.
abstract: Dimerumic acid (DMA) is contained in Monascus anka and Monascus pilosus fermented products. The purpose of this study was to evaluate the effect of DMA against salicylic acid (SA)- and tert-butylhydroperoxide (t-BHP)-induced oxidative stress and cytotoxicity in the liver, using rat liver microsomes and isolated rat hepatocytes. DMA was extracted from monascus-garlic-fermented extract using M. pilosus. In rat liver microsomes, 1 microM DMA decreased SA-induced lipid peroxidation but did not affect the production of the oxidative metabolite of SA via CYP. In isolated rat hepatocytes, 1 microM DMA decreased SA-induced lipid peroxidation and chemiluminescence (CL) generation and the intracellular glutathione-reduced form/oxidized form (GSH/GSSG) ratio in the presence of 1 microM DMA was higher than that without DMA; however, 100 microM DMA suppressed the leakage of lactate dehydrogenase (LDH). On the other hand, t-BHP-induced lipid peroxidation, CL generation, and LDH leakage were prevented by 100 microM DMA. Thus, DMA showed an antioxidative effect in hepatocytes and protected against hepatotoxicity by suppressing oxidative stress without affecting CYP enzymes.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Yamashiro
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Shiraishi
authors.forename: Toru
authors.initials: T
authors.lastname: Fuwa
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Horie
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000633:toxicity; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D000975:Antioxidants; D016877:Oxidants; D010879:Piperazines; D012459:Salicylates; C001011:dimerum acid; D003577:Cytochrome P-450 Enzyme System; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione