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.