PP63 - Xanthine oxidase regulates pesticides-induced oxidative stress in rat polymorphonuclear leukocytes via NOS-independent pathway

Abstract

Oxidative stress is reported to be a key malefactor in pesticides-induced toxicity. Xanthine oxidase (XO) is implicated in pesticides-induced oxidative stress and nitric oxide (NO) plays a decisive role in XO-mediated toxicity. The study aimed to investigate the role of XO in pesticides-induced (combined maneb/MB and paraquat/PQ-induced) oxidative stress in polymorphonuclear leucocytes (PMNs) and its subsequent relationship with inducible NO synthase (iNOS)-mediated nitrosative stress. Male Wistar rats were administered with MB and PQ, twice a week, for 2 weeks along with vehicles. In a few sets, rats were also treated with aminoguanidine/AG (an iNOS inhibitor), allopurinol/AP (a XO inhibitor), pyrrolidine dithiocarbamates/PDTC (a NF-κB inhibitor), pentoxyphylline/PTX (a TNF-α inhibitor) and dexamethasone (an anti-inflammatory drug) along with respective controls. While pesticides augmented reactive oxygen species (ROS), lipid peroxidation (LPO) and nitrite production, iNOS expression and superoxide dismutase (SOD) and XO activity, catalase activity was attenuated. AP ameliorated pesticides-induced changes in ROS, LPO, SOD, catalase and XO however nitrite content and iNOS remained unaltered. AG, on the other hand, alleviated pesticides-induced alterations in LPO, nitrite, catalase and iNOS in the PMNs but ROS, SOD and XO were found to be unchanged. Furthermore, PDTC, PTX and DEX also attenuated pesticides-induced increase in XO expression in the PMNs. The results demonstrate that XO mediates pesticides-induced oxidative stress in the PMNs through iNOS-independent mechanism, which might be regulated by inflammatory cytokines.