MODULATORY EFFECT OF ORGANOTIN COMPOUNDS ON HEPATIC AND CENTRAL NERVOUS SYSTEM’S REDOX HOMEOSTASIS AND APYRASE ACTIVITIES IN RATS.

Abstract

This study sought to evaluate and compare the modulatory effect of the organotin compounds (OTCs) - dibultytin dilaurate (DBD), tributyltin chloride (TBC) and triphenyltin chloride (TPT) on redox homeostasis and the activities of the purinergic enzymes- nucleoside triphosphate diphosphohydrolase (NTPDase) and ecto-5’-nucleotidase in rat brain, spinal and hepatic tissues under in vitro and in vivo situations. The possible in vitro modulation of redox homeostasis evoked by the OTCs were evaluated by assessment of their radical scavenging abilities as well as their influence on the production of both basal and pro-oxidant-induced lipid peroxidation products in the selected tissues. In addition, the effects of the organotins on the activities of the purinergic enzymes were also determined in vitro. Furthermore, the effect of the OTCs on redox status and activities of the purinergic enzymes in rat models were also assessed. The results showed that both TBC and TPT evoked a pro-oxidative-like effect on both basal and pro-oxidant-induced lipid peroxidation while DBD exhibited inhibitory effects on the production of lipid peroxidation products by mechanism(s) that is not related to its ability to scavenge radicals. Also, while TBC and TPT markedly inhibited the activities of the purinergic enzymes under in vitro condition, DBD had no effect on the activities of the purinergic enzymes. Moreso, under in vivo situations, all the OTCs markedly increased lipid peroxidation, decreased reduced glutathione content and decreased the ability of the tissues evaluated to scavenge radicals in a dose dependent manner. Finally, there was a dose dependent inhibition of the activities of the purinergic enzymes in rats administered with the OTCs. Apparently, the organotins tested in this study evoked their deleterious effects in mammals through mechanisms that ultimately lead to a disturbed redox homeostasis and altered activities of enzymes that partake in the purinergic signalling systems. This may explain in part the contributing mechanisms for the observed neuro- and hepatotoxicities of the OTCs.