ROLE OF DIPHENYL DISELENIDE IN CARBOFURAN – INDUCED DISTURBED REDOX SYSTEMS UNDER IN VITRO AND IN VIVO CONDITIONS IN RATS

Abstract

One of the mechanisms by which carbofuran (CF) exerts its toxicity is via oxidative stress, thus leading to drastic decrease in the activities of antioxidant enzymes and pool of vital antioxidant components in mammalian systems. To combat these hazardous effects, a very potent source of antioxidant pool would be of utmost importance. The present study was designed to investigate the influence of diphenyl diselenide (DPDS) – a synthetic organoselenium compound with antioxidant properties – on the oxidative stress induced by carbofuran under in vitro and in vivo conditions. The possible antioxidative or prooxidative effects of DPDS and CF, respectively, on lipid peroxidation were investigated in vitro in the presence and absence of various pro-oxidants such as iron, sodium oxalate, sodium nitroprusside and 3- nitropropionic acid. For the in vivo assay, adult female rats (180-200g) (n = 40) were randomly divided into eight groups (n = 5): and treated with either CF (1, 10, 100 ppm) alone or in combination with 3 mg/kg DPDS. The treatment lasted for 100 days; and the effects of CF and DPDS compounds were evaluated in the treated animals. The in vitro results showed that CF caused an increase in lipid peroxidation in the presence of prooxidants, but exhibited a somewhat antioxidant effect in the absence of these prooxidants. The prooxidative effect of CF was attenuated in the presence of DPDS. The in vivo results revealed a significant increase in TBARS production in cerebral, hepatic and renal tissues; and increase in plasma levels of ALT, AST, urea and creatinine in CF-treated groups. However, DPDS markedly caused a decrease in TBARS formation; and plasma levels of levels of ALT, AST, urea and creatinine. Additionally, there was a significant reduction in GSH level and radical scavenging ability in tissues of CF-treated groups when compared to the control group. More so, the activities of NTPDase, 5′-nucleotidase, δ-aminolevulinic acid dehydratase (ALA-D) and Na+/K+-ATPase were significantly reduced in CF treated experimental animals and DPDS was able to restore the activities of these enzymes to control level. The results from the present investigation suggest that CF evoked deleterious effects in the experimental animals through mechanisms that ultimately lead to a disturbed redox system and altered activities of some purinergic enzymes which could be considered as a contributing factor to its nephro- and hepato-toxicity. More so, the results showed that treatment with DPDS was effective in protecting against cerebral, renal and hepatic damage induced by CF-mediated toxicity.