Triphenyl tin hepatotoxicity in rats

Area of Science:

• Toxicology
• Hepatology
• Drug Metabolism

Background:

• Triphenyl tin (TPT) is a known organotin compound.
• Hepatic microsomal enzymes and biliary excretion are critical for xenobiotic metabolism and elimination.

Purpose of the Study:

• To investigate the effects of triphenyl tin (TPT) on hepatic microsomal enzyme activities and biliary excretion in rats.
• To explore the role of glutathione conjugation in TPT-induced changes in sulfobromophthalein (BSP) excretion.

Main Methods:

• Rats were treated with triphenyl tin (TPT) at 1 mg/kg i.p. daily for 3 days.
• In vitro hepatic microsomal aniline hydroxylase and aminopyrine N-demethylase activities were measured.
• Biliary excretion of sulfobromophthalein (BSP), procainamide ethobromide, and amaranth was assessed.
• Hepatic glutathione-S-transferase activity was also evaluated.

Main Results:

• TPT treatment significantly reduced hepatic microsomal aniline hydroxylase and aminopyrine N-demethylase activities.
• Biliary excretion of sulfobromophthalein (BSP) was significantly decreased in TPT-treated rats.
• TPT did not affect bile flow, liver weight, serum enzyme activities, or the biliary excretion of procainamide ethobromide and amaranth.
• TPT inhibited rat liver glutathione-S-transferase activity.

Conclusions:

• Triphenyl tin (TPT) impairs hepatic microsomal enzyme activities and reduces the biliary excretion of sulfobromophthalein (BSP) in rats.
• Reduced glutathione conjugation, due to TPT's inhibition of glutathione-S-transferase, likely contributes to the decreased biliary BSP excretion.
• TPT's effects are specific to certain metabolic pathways, as other excretory functions remained unaffected.