Non-Steroidal Anti-Inflammatory Drugs and Vitamin C in the Rotenone Induced Nigrostriatal Damage in Mice

Abstract

Abstract:The nigrostriatal pathway is a dopaminergic pathway that connects the substantia nigra with the dorsal striatum.Loss of dopamine neurons in the substantia nigra is one of the main pathological features of Parkinson's disease, leading to a marked reduction in dopamine function in this pathway. This study aimed at evaluating the protective role of two antiinflammatory drugs, indomethacin and nimesulide separately or in combination with vitamin C against biochemical disturbances, brain damage and motor impairment in rotenone-induced mice model of Parkinson's disease. Animals were divided into 7 groups. 1 st received the vehicle (DEMSO); 2 nd received rotenone (1.5 mg/kg); 3 rd received rotenone then were left for two weeks recovery; 4 th rotenone + indomethacin (10 mg/kg); 5 th received rotenone + indomethacin in combination with vitamin C (25 mg/kg). 6 th received rotenone + nimesulide (10 mg/kg); group 7 received rotenone + nimesulide in combination with vitamin C. All treatments were given subcutaneously three times per week for one month. Rotenone treatment caused significant Increases in brain malondialdehyde (MDA), nitric oxide (NO), but induced significant decreases in brain reduced glutathione (GSH) level, acetylcholinesterase (AChE) activity, dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels. These changes lasted for two weeks after the termination of rotenone treatment. Histologically, Rotenone caused degeneration of neurons in striatum, cellular infiltration, atrophy, pyknosis, necrosis, as well as focal gliosis in cerebral cortex and pyknosis of pyramidal cells in the hippocampus. Furthermore, rotenone treatment caused a significant impairment in the motor function of the mice (stair test). Co-administration of indomethacin or nimesulide separately or in combination with vitamin C to rotenone treated mice resulted in alleviation of biochemical and motor activity but not the histological disturbances caused by rotenone treatment alone.

Grape Seed Extract Exerts an Anti-Apoptotic Effect and Attenuates the Decrease in Striatal Tyrosine Hydroxylase in Rotenone-Treated Mice

“…Rotenone also caused a significant increase in brain nitric oxide, a finding that is in agreement with previously published observations [33][34][35]. We have also shown that rotenone resulted in increased nitric oxide release and prominent inducible nitric oxide synthase (iNOS) immunostaining in the striatum and SNpc [33][34][35]59].…”

“…There were also α-synuclein-like deposits in the remaining SNpc neurons [29,49]. Other studies have shown that rotenone given to mice via subcutaneous or intragastric routes was capable of inducing nigrostriatal degeneration [31][32][33][34][35]52]. The mouse model of rotenone administration was used in this study.…”

“…treated mice. Rotenone also caused a significant impairment in the motor function of mice [33][34][35]. Much more important is that this dosing regimen did not cause protracted illness and thus allowed for careful assessment of the mouse's motor behavior.…”

“…Rotenone causes neuronal cell death via increased oxidative stress [53], a major pathogenetic mechanism contributing to DA-ergic neurodegeneration in human PD [9,54]. Studies thus showed the increased formation of reactive oxygen metabolites [55], increased lipid peroxidation products [33][34][35], and protein carbonyls [56] in the rodent brain after rotenone treatment. Rotenone activates microglia that release reactive oxygen metabolites via myeloperoxidase enzyme [57].…”

“…In this study, the potential protective effect of a standardized GSE rich in proanthocyanidins was investigated in an experimental model of PD induced in mice by the administration of the pesticide rotenone. The latter has been widely used to model human PD in rats [28,29] and mice [30][31][32][33][34][35].…”