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Mirjana Djukic

University of Belgrade, Serbia

Title: Oxidative/Nitrosative stress underlying neurotoxic mechanisms of paraquat

Biography

Biography: Mirjana Djukic

Abstract

Paraquat (PQ) neurotoxicity has not thoroughly investigated. Red-ox metabolism of PQ2+ results in superoxide anion radical (O2•) formation. Consequent free radical reactions escalate due to stable resonance radical structure (PQ•+). The OS/NS-associated neurotoxic pathways of PQ were investigated in striatum of Wistar rats after single intrastriatal administration of PQ+ and applied pretreatments, including: N-nitro-L-arginine-methyl ester (L-NAME); 2-amino-5-phosphonovaleric acid (APV); glutathione reductase (GR); and naloxone. Reversible Parkinson’s disease symptoms were observed in PQ group. Contrary to PQ, APV+PQ and GR+PQ groups, initially high O2• reached the normal values in L-name+PQ and naloxone+PQ groups, on 7th day. Superoxide dismutase (SOD) activity declined in L-name+PQ, naloxone+PQ and APV+PQ groups. Initially low SOD activity reached normal values on 7th day in Pq and GR+PQ groups. Lipid peroxidation was the highest in PQ, L-name+PQ and GR+PQ groups. Glutathione (GSH) depletion was considerable in L-name, APV and naloxone pretreated rats across the time. Increased GSH values were achieved in PQ and GR+PQ group on the 7th day. Glutathione peroxidase (GPx) activity was inhibited by GR (within 24 hours) and naloxone; elevated GPx activity declined with the time in APV+PQ and L-name+PQ; while it was high in PQ group until the 7th day. In conclusion, inhibitors of NO-synthase, N-methyl-D-aspartate (NMDA) and opioid receptors, reduced SOD and GPx activities and depleted GSH. Rise of O2• occurred in APV and GR pretreated groups (twice higher than in PQ group), on 7th day, although APV did not influence LPO.