PROTECTIVE ROLE OF DIPHENYL DISELENIDE IN THE REDOX IMBALANCE ASSOCIATED WITH PENTACHLOROPHENOL-MEDIATED TOXICITY

Abstract

The present study sought to evaluate the likely protective role of diphenyl diselenide (DPDS) on the redox imbalance associated with pentachlorophenol (PCP) toxicity in rat cerebral, hepatic, spinal and renal tissues in vitro and in vivo. The effects of PCP on lipid peroxidation were investigated in vitro in the presence of various pro-oxidants such as 3-nitropropionic acid, iron (II), hydrogen peroxide, quinolinic acid, sodium nitroprusside and sodium oxalate. In the in vivo study, forty (n=5) experimental rats (200-250g) were orally administered with 1, 10, and 100 ppm solutions of pentachlorophenol for 100 days and were treated along with 3mg/kg body weight DPDS. The effect of PCP on cerebral, hepatic, spinal and renal lipid status and the activities of the purine-dependent signalling enzymes -NTPDase and 5’-nucleotidase were examined by measuring the level of formation of thiobarbituric acid reactive species and the activities of nucleotide hydrolysing enzymes respectively. The experimental results showed that PCP inhibited cerebral, spinal, hepatic and renal lipid peroxidation in vitro in a concentration-dependent manner by preventing the formation of thiobarbituric acid reactive substances. In contrast, the in vivo result revealed that PCP induced cerebral, hepatic and renal lipid peroxidation as typified by an increased amount of malondialdehyde (MDA) production in these tissues. The cerebral, hepatic and renal glutathione level as well as radical scavenging ability of the tested tissues were significantly reduced in PCP-treated experimental animals whereas DPDS restored these alterations to control level. Moreso, the cerebral, hepatic and renal activities of NTPDase, 5’-nucleotidase, δ-aminolevulinic acid dehydratase (δ-ALAD) and Na+/K+-ATPase were significantly reduced in PCP-treated experimental animals and DPDS was able to restore the activities of these enzymes to control level. Furthermore, an increase in the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, and triglycerides were also observed in PCP-treated experimental animals while DPDS reduced the activities of the ALT and AST enzymes as well as the concentration of the urea, creatinine and triglycerides in the serum. The results from the present investigation suggest that PCP tested in this study evoked the deleterious effects in mammals through mechanisms that ultimately lead to a disturbed redox system and altered activities of some purine-dependent signalling enzymes which could be considered as a contributing factor to its reno- and hepatotoxicity. The results in this work showed that treatment with DPDS was effective in protecting against cerebral, renal and hepatic damage induced by PCP-mediated toxicity.