TOXICITY STUDIES OF A SYNTHETIC ANTIOXIDANT, 2,2'-METHYLENEBIS (4-ETHYL-6-TERT-BUTYLPHENOL) IN RATS 2. UNCOUPLING EFFECT ON OXIDATIVE PHOSPHORYLATION OF LIVER MITOCHONDRIA

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Effects of 2, 2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) on hepatic mitochondrial oxidative phosphorylation in vitro, and on hepatic peroxisomal enzymes activities and microsomal mixed-function oxidase activities were studied. 1. A low concentration of MBEBP, less than 50μM, increased state 4 respiration and decreased state 3 respiration. However, a higher concentration of MBEBP, greater than 100μM, acted as a respiratory inhibitor. Therefore, MBEBP was found to act as an uncoupler of oxidative phosphorylation in rat liver mitochondria. 2. MBEBP significantly decreased peroxisomal enzymes, cyanide-insensitive palmitoyl-CoA oxidizing activity and catalase activity in the livers of rats fed 0.2, 1.0 or 5.0% MBEBP for 4 weeks. 3. In microsomal enzyme assay, NADPH cytochrome c reductase activity was significantly increased, however, cytochrome P-450, cytochrome b_5 levels, aminopyrine N-demethylase and benzo [a] pyrene hydroxylase activities were not significantly increased in the livers of rats fed 1.0 or 5.0% MBEBP for 4 weeks. The weight loss and the decrease of serum triglyceride level observed in the MBEBP-treated rats seemed to be caused by its uncoupling effects, which might also be the cause of the testicular damage induced by MBEBP.
日本トキシコロジー学会の論文
1993-02-25