Effects of pretreatment with SKF-525A on triphenyltin metabolism and toxicity in mice.

:The effects of cytochrome P-450 inhibition by alpha-phenyl-alpha-propylbenzeneacetic acid 2-[diethylamino]-ethyl ester hydrochloride (SKF-525A), which inhibits the activity of a number of cytochrome P-450s, on triphenyltin metabolism and toxicity in mice were studied. At 24 h after triphenyltin administration, the triphenyltin levels in the tissues of SKF-525A-pretreated mice were about three times of those in the tissues of SKF-525A-untreated mice and the ratio of metabolites to parent triphenyltin in the tissues of SKF-525A-pretreated mice was lower than those in the tissues of SKF-525A-untreated mice. These data indicate that the pretreatment of SKF-525A decelerated the triphenyltin metabolism and increased triphenyltin accumulation in the tissues of mice. Although triphenyltin did not affect plasma glucose levels of in the SKF-525A-untreated mice, the triphenyltin produced marked hyperglycemia in SKF-525A-pretreated mice. These results suggest that the inhibition of cytochrome P-450 system enzymes by SKF-525A affects the metabolism and toxicity of triphenyltin and has a key role in inducing the hyperglycemic action of triphenyltin, i.e. by increasing triphenyltin accumulation in the mice.

Ohhira S ，Matsui H ，Watanabe K 《TOXICOLOGY LETTERS》

Effects of pretreatment with cytochrome P-450 inducers, especially phenobarbital on triphenyltin metabolism and toxicity in hamsters.

Ohhira S ，Matsui H ，Watanabe K 《TOXICOLOGY》

Effect of SKF-525A on liver metabolism and hepatotoxicity of tri- and dibutyltin compounds in mice.

Ueno S ，Suzuki T ，Susa N ，Furukawa Y ，Sugiyama M ... -  《ARCHIVES OF TOXICOLOGY》

Inhibition of cocaine oxidative metabolism attenuates endotoxin potentiation of cocaine mediated hepatotoxicity.

Labib R ，Turkall R ，Abdel-Rahman MS 《TOXICOLOGY》

In vitro metabolism of isoline, a pyrrolizidine alkaloid from Ligularia duciformis, by rodent liver microsomal esterase and enhanced hepatotoxicity by esterase inhibitors.

Tang J ，Akao T ，Nakamura N ，Wang ZT ，Takagawa K ，Sasahara M ，Hattori M ... -  《DRUG METABOLISM AND DISPOSITION》