INFLUENCE OF CARBOFURAN AND PENTACHLOROPHENOL ON THE REDOX STATUS AND PURINERGIC SIGNALING IN RATS

Abstract

Pesticides are one of the few toxic substances deliberately released into the environment to control pests. However, their non-selectivity towards intended target species often results in adverse health effects in these species including humans. The precise biochemical and molecular phenomenon of pesticides toxicity in non-target species can be complex and far from being completely elucidated. Consequently, the present study sought to evaluate the likely participation of disturbed redox imbalances as well as altered purinergic signaling as possible components of toxicological mechanisms elicited by two pesticides carbofuran (CF) and pentachlorophenol (PCP). The effect of both pesticides on redox homeostasis were evaluated under in vitro condition by assessing their ability to induce/enhance lipid peroxidation and Reactive Oxygen Species (ROS) production in both hippocampal slices and different complexes of isolated liver mitochondria. Furthermore, the modulatory effects of both pesticides on the activity of purinergic signaling enzymes such as Na+/K+-ATPase, 5’-nucleotidase (5-NT), nucleoside triphosphate disphosphorylase (NTPDase) were evaluated. Finally, different doses of CF (1- 8 mg /kg body weight) and PCP (37 – 300 mg/kg body weight) were administered intraperitoneally into adult albino rats and the redox status, as well as the activities of the purinergic enzymes were assessed. Data obtained revealed that under in vitro condition, PCP exerted considerable inhibitory effect on the peroxidation of cerebral and hepatic lipids subjected to various oxidative assaults while CF had no significant effect. Although both pesticides neither scavenged DPPH radicals nor reduced Fe3+ nor chelated Fe2+, PCP but not CF decreased ROS production in hippocampal slices and isolated mitochondria. Also, PCP mediated ROS production in the mitochondria by inhibiting the activities of both complex I and II activity in the organelle. Furthermore, PCP markedly inhibited all purine-cleaving enzymes tested whereas these enzymes iii were insensitive to CF. Conversely, under in vivo condition, both pesticides evoked an increase in lipid peroxidation and activities of 5-NT and NTPDase whereas the activities Na+/K+-ATPase was inhibited. Summarily, the results of this study showed that the toxicological response of mammalian systems associated with pesticides toxicity can be complex and in vitro data may not be translatable in vivo. However, the pathophysiology of CF and PCP toxicity under in vivo conditions appear to be intrinsically associated with disturbed redox systems and altered purinergic signaling.