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.
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.
Takagi
A
A
Division of Toxicology, National Institute of Hygienic Sciences, Tokyo, Japan.
Kawasaki
N
N
Momma
J
J
Aida
Y
Y
Ohno
Y
Y
Hasegawa
R
R
Kurokawa
Y
Y
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008830:Microbodies / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D002084:Butylated Hydroxytoluene; D002374:Catalase; D009251:NADPH-Ferrihemoprotein Reductase; C030577:2,2'-methylenebis(ethyl-6-tert-butylphenol)