Stimulation of lipid peroxidation and impairment of glutathione-dependent defense system in wistar rats treated with cryptopine, a rare non-narcotic opium alkaloid

Abstract

The present study was designed to evaluate the effect of repeated oral administration of cryptopine at differential dosing regimens (50, 100, 150, 200 mg/kg bwt) in vivo on lipid peroxide measures, glutathione levels (GSH) and activity of glutathione S-transferase (GST) and glutathione reductase (GR) in the liver, spleen, kidney and lung of Male Wistar rats after a 5 day treatment period. In all the tissues examined, we observed an increase in lipid peroxidation and a decline in glutathione content and activity of glutathione S-transferase and glutathione reductase in a dose-dependent manner. The decrease in GSH content did not definitively correlate with a concomitant increase of lipid peroxidation in all the tissues. Our results ensemble that the enhancement of lipid peroxidation in the tissues investigated is a consequence of depletion of glutathione to certain critical levels and impairment of the glutathione-dependent enzyme systems viz. GST and GR. Our study potentiates that decreased levels of GSH may lead to lipid peroxidation, one of the key events in cellular damage. The inhibition of GST also suggests that the detoxification of the alkaloid could be suppressed following acute exposures. Conclusively, it appears that cryptopine in vivo disturbs the cellular defense system, so that it tips in the direction of autoxidative lipid peroxidation, producing cytotoxicity.