Oxidative and nitrosative stress: Mediators of diquat neurotoxicity

Abstract

Most commonly observed central nervous system (CNS) effects induced by systemic toxicity of herbicide diquat (DQ) are general depression and lethargy. Generally, it is accepted that DQ exerts its toxicity through the production of superoxide anion radical (O2 ●-) during its redox metabolism in the presence of molecular oxygen, which further initiates radical chain reaction, contributing developing of oxidative stress (OS) as well. Mechanisms of DQ neurotoxic effect is not rationalized till now. The objective of the study was to examine whether OS contributes to DQ neurotxicity. For this purpose, male Wistar rats were intrastriataly (i.s.) treated with DQ and oxidative status parameters such as: superoxide anion radical (O2 ●-); nitrates (NO3 -), as a final metabolite of reactive nitogen species; malondialdehyde (MDA), an indicator of lipid peroxidation; activity of superoxide dismutase (SOD); glutathione peroxidase (GPx), and glutathione (GSH), were measured in the hippocampus at 30 minutes, 24 hours and 7 days post treatment. Noteworthy, mortality rate (30 - 40 %) was observed in the group of rats treated with DQ, within 2-3 hours after awakening from anesthesia. Additionally, lethargy was the only neurological symptom observed in that group. Analyzed parameters indicate that OS mediates DQ neurotxicity, which is documented with significant increase of lipid peroxidation.

Najčešće zapaženi efekti sistemskog trovanja herbicidom dikvatom (DK) na centralni nervni sistem (CNS) su opšta depresija i letargija. Opšte je prihvaćeno da se toksičnost DK ostvaruje posredstvom povećanog stvaranja superoksid anjon radikala (O2 ●-) tokom njegovog redoks metabolizma, u prisustvu molekularnog kiseonika, koji dalje inicira lančanu reakciju radikalskog tipa i razvoj oksidativnog stresa (OS). Do danas mehanizmi neurotoksičnog efekta DK nisu u potpunosti poznati. Cilj ove studije je bio da ispitamo da li OS posreduje u neurotoksičnosti indukovanoj DK. Eksperiment je sproveden na mužjacima Wistar pacova, intrastrijatalno tretiranih (i.s.) DK. Parametri oksidativnog statusa, kao što su: superoksid anjon radikal (O2 ●-), nitrati (NO3 -), kao finalni metaboliti reaktivnih vrsta azota; malondialdehid (MDA), indikator lipidne peroksidacije; aktivnost enzima; superoksid dizmutaze (SOD) i glutation peroksidaze (GPx); i glutation (GSH) mereni su u hipokampusu, 30 minuta, 24 sati i 7 dana posle tretmana. Stopa smrtnosti od 30 do 40 % ustanovljena je u grupi pacova tretiranih DK, tokom 2-3 sata od buđenja iz anestezije. Dodatno, pacovi ove grupe su pokazali neurološke simptome letargije. Značajno povećana lipidna peroksidacija pokazuju da OS posreduje u neurotoksičnom odgovoru indukovanom i.s. primenom DK.