The effect of pre-treatment with l-name on glutathione and glutathione peroxidase in parquat-induced neurotoxicity in rat striatum

Abstract

Contact herbicide paraquat (DQ) is bipyridylium compound, which undergoes redox metabolism; hence enlarged in humans radical production mediated its toxicity. Target organs of systemic effect of PQ poisoning are lung and kidney. The mechanism of PQ-induced neurotoxicity is not elucidated till now. The objective of our study was to examine the role of nitric oxide (NOx) in PQ-induced neurotoxicity, primarily focusing on glutathione cycles [total glutathione content (GSH) and glutathione peroxidase (GPx) activity]. In order to investigate the role of NOx in oxidative stress (OS) and/or nitrosative stress (NS) response to PQ neurotoxicity, we used NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) in the pretreatment of PQ administration. Study was conducted on Wistar rats randomly divided in groups (n=8 for controls and n=24 for experimental groups) depending on the applied treatments. The tested compounds were intrastriatally (i.s.) administered. Measuring of GSH content and GPx activity was performed at 30 min, 24 hours and 7 days after treatments. Parkinsonism’s like symptoms were observed only in the group of rats treated with PQ. The L-NAME protected animals from PQ-induced neurotoxicity, which could be concluded from the absence of Parkinsonism’s like symptoms and reduced OS/NS response in the striatum of rats pretreated with L-NAME.

Kontaktni herbicid parakvat (PK) je dipiridinsko jedinjenje, koje podleže redoks metabolizmu i svoju toksičnost ispoljava posredstvom povećanog stvaranja slobodnih radikala. Ciljni organi sistemskog toksičnog efekta PK kod čoveka su pluća i bubrezi. Mehanizam PKindukovane neurotoksičnosti do sada još uvek nije u potpunosti rasvetljen. Cilj našeg rada bio je da se ispita uloga azot oksida (NOx) u neurotoksičnosti PK, sa posebnim osvrtom na glutationski ciklus [glutation (GSH) i enzim glutation peroksidazu (GPx)]. U cilju da se istraži uloga NOx u oksidativnom stresu (OS) i / ili nitrosativnom stresu (NS), kao odgovoru na neurotoksičnost PK. U predtretmanu parakvatom koristili smo NG-nitro- L-arginin metil estar (L-NAME), neselektivni inhibitor azot oksid sintetaze (NOS), aplikovan je pre davanja PQ . Studija je sprovedena na pacovima Wistar soja nasumice podeljenim u grupe (n = 8 za kontrolnu grupu i n = 24 za eksperimentalne grupe) u zavisnosti od tretmana. Testirana jedinjenja su intrastrijatalno (i.s.) aplikovana. Merenje sadržaja GSH i aktivnosti GPx izvršena su 30 min, 24 sata i 7 dana posle tretmana. Parkinsonizam je kao simptom primećen samo u grupi pacova tretiranih PK - om. L-NAME je ispoljio zaštitni efekat kod životinja kod kojih je i.s. davan PK, što bi se moglo zaključiti na osnovu odsustva simptoma parkinsonizma i smanjenog OS/NS odgovora u strijatumu u grupi pretretiranoj sa L-NAME.