Dimerumic acid protected oxidative stress-induced cytotoxicity in isolated rat hepatocytes

• Published in: Cell biology and toxicology Vol. 24; no. 4; pp. 283 - 290
• Main Authors: Yamashiro, Jun-ichi, Shiraishi, Sumihiro, Fuwa, Toru, Horie, Toshiharu
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-08-2008; Springer Nature B.V
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Survival; Chemiluminescence; Cytochrome P-450 Enzyme System - metabolism; Cytoprotection; Cytotoxicity; Dose-Response Relationship, Drug; Enzymes; Glutathione - metabolism; Hepatocytes - drug effects; Hepatocytes - enzymology; Hepatocytes - metabolism; Hepatocytes - pathology; Hepatotoxicity; L-Lactate Dehydrogenase - metabolism; Life Sciences; Lipid Peroxidation - drug effects; Liver; Male; Metabolites; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Monascus; Monascus anka; Oxidants - toxicity; Oxidative stress; Oxidative Stress - drug effects; Peroxidation; Pharmacology/Toxicology; Piperazines - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Salicylates - toxicity; tert-Butylhydroperoxide - toxicity; Toxicity; Dimerumic acid; Oxidative stress; Isolated rat hepatocyte; Antioxidant
• ISSN: 0742-2091; 1573-6822
• DOI: 10.1007/s10565-007-9037-7

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 μM 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 μM 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 μM DMA was higher than that without DMA; however, 100 μM 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 μM DMA. Thus, DMA showed an antioxidative effect in hepatocytes and protected against hepatotoxicity by suppressing oxidative stress without affecting CYP enzymes.