Inhibition of hepatic microsomal monooxygenase system by organotins in vitro in freshwater fish

• Published in: Aquatic Toxicology
• Main Authors: Fent, Karl, Bucheli, Thomas D.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 1994
• Subjects: freshwater fish; tributyltin; triphenyltin; microsomal monooxygenase system; cytochrome P450; NADPH cytochrome P450 reductase; NADH cytochrome b5 reductase; Anguilla anguilla; European eel
• Online Access: https://doi.org/10.1016/0166-445x(94)90024-8

The interaction in vitro of organotins tributyltin (TBT) and triphenyltin (TPT) with the hepatic microsomal monooxygenase systems in the freshwater fish, rainbow trout ( Oncorhynchus mykiss ), European eel ( Anguilla anguilla ), and bullhead ( Cottus gobio ) was studied. Hepatic microsomes were incubated in vitro with TBT and TPT and various components analyzed. Ethoxyresorufin O -deethylase (EROD) activity was strongly inhibited by TBT and TPT in a concentration-dependent manner in all fish. Rainbow trout microsomes were more sensitive than were eel or bullhead microsomes. Total inhibition of EROD activity occurred both at 0.5 mM TBT and TPT in rainbow trout, whereas I mM decreased EROD activity to 15% (TBT) or 3% (TPT) in eel, and 35% (TBT) or 18% (TPT) in bullhead, respectively. As this effect may be caused by inhibition of different components of the microsomal electron transport system, different enzymes were studied separately. In all fish, both organotins led to a time- and concentration-dependent decrease in spectral total microsomal P450 content, and formation of cytochrome P420. TPT led to a greater inactivation of P450 enzyme than TBT, and induced a 50% loss in all fish at 0.08 mM TPT, whereas in case of TBT a 50% loss occurred at 0.18 mM in rainbow trout, 0.30 mM in bullhead, and 0.83 mM in eel. Cytochrome b 5 content was not affected, but both organotins led to an almost selective inhibition of either NADH or NADPH cytochrome c reductase activity in trout and eel, or of both in bullhead. Whereas TBT inhibited NADH cytochrome c reductase, TPT acted strongly on NADPH cytochrome e reductase. The study demonstrates species-related significant and selective effects of TBT and TPT on different components of the microsomal monooxygenase system in freshwater fish. This leads to inactivation of native enzymes and inhibition of enzyme activities.