INHIBITION OF HEPATIC-MICROSOMAL MONOOXYGENASE SYSTEM BY ORGANOTINS IN-VITRO IN FRESH-WATER FISH

The interaction in vitro of organotins tributyltin (TBT) and triphenyl tin (TPT) with the hepatic microsomal monooxygenase systems in the fre shwater fish, rainbow trout (Oncorhynchus mykiss), European eel (Angui lla anguilla), and bullhead (Cottus gobio) was studied. Hepatic micros omes were incubated in vitro with TBT and TPT and various components a nalyzed. Ethoxyresorufin O-deethylase (EROD) activity was strongly inh ibited by TBT and TPT in a concentration-dependent manner in all fish. Rainbow trout microsomes were more sensitive than were eel or bullhea d microsomes. Total inhibition of EROD activity occurred both at 0.5 m M TBT and TPT in rainbow trout, whereas 1 mM decreased EROD activity t o 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 differen t components of the microsomal electron transport system, different en zymes were studied separately. In all fish, both organotins led to a t ime- 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 fi sh 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. Cytochro me b5 content was not affected, but both organotins led to an almost s elective inhibition of either NADH or NADPH cytochrome c reductase act ivity in trout and eel, or of both in bullhead. Whereas TBT inhibited NADH cytochrome c reductase, TPT acted strongly on NADPH cytochrome c reductase. The study demonstrates species-related significant and sele ctive effects of TBT and TPT on different components of the microsomal monooxygenase system in freshwater fish. This leads to inactivation o f native enzymes and inhibition of enzyme activities.