Non-Steroidal Anti-Inflammatory Drugs and Vitamin C in the Rotenone Induced Nigrostriatal Damage in Mice
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 anti-inflammatory 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); 2nd received rotenone (1.5 mg/kg); 3rd received rotenone then were left for two weeks recovery; 4th rotenone + indomethacin (10 mg/kg); 5th received rotenone + indomethacin in combination with vitamin C (25 mg/kg). 6th 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.
Nagi Ali Ibrahim,
Omar Mohamed Abdel-Salam,
Yasser Ashry Khadrawy,
Amal Mohamed Hashem,
Eman Mohamed Sameer,
Non-Steroidal Anti-Inflammatory Drugs and Vitamin C in the Rotenone Induced Nigrostriatal Damage in Mice, European Journal of Clinical and Biomedical Sciences.
Vol. 3, No. 4,
2017, pp. 67-79.
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