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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.

Abstract
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 50 microM, increased state 4 respiration and decreased state 3 respiration. However, a higher concentration of MBEBP, greater than 100 microM, 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 b5 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.
AuthorsA Takagi, N Kawasaki, J Momma, Y Aida, Y Ohno, R Hasegawa, Y Kurokawa
JournalThe Journal of toxicological sciences (J Toxicol Sci) Vol. 18 Issue 1 Pg. 49-55 (Feb 1993) ISSN: 0388-1350 [Print] Japan
PMID8474150 (Publication Type: Journal Article)
Chemical References
  • Triglycerides
  • Butylated Hydroxytoluene
  • Catalase
  • NADPH-Ferrihemoprotein Reductase
  • 2,2'-methylenebis(ethyl-6-tert-butylphenol)
Topics
  • Animals
  • Butylated Hydroxytoluene (analogs & derivatives, toxicity)
  • Catalase (metabolism)
  • In Vitro Techniques
  • Male
  • Microbodies (enzymology)
  • Microsomes, Liver (enzymology)
  • Mitochondria, Liver (drug effects, metabolism)
  • NADPH-Ferrihemoprotein Reductase (metabolism)
  • Oxidative Phosphorylation (drug effects)
  • Oxygen Consumption (drug effects)
  • Rats
  • Rats, Wistar
  • Testis (drug effects)
  • Triglycerides (blood)

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