TELMISARTAN ALLEVIATES NITROSATIVE STRESS IN TURN DOPAMINERGIC DEGENERATION IN MICE MPTP MODEL OF PARKINSONISM–BIOCHEMICAL AND HISTOPATHOLOGICAL EVIDENCES
Keywords:
MPTP, Telmisartan, Oxidative stress, Dopaminergic degenerationAbstract
Objective: Telmisartan (TEL), an angiotensin type 1 receptor blocker, exerts neuroprotection in MPTP induced Parkinson's disease. The present study was aimed to investigate its effects on oxidative stress markers–inducible nitric oxide synthase (iNOS), nitric oxide (NO) and reduced glutathione (GSH) content in C57BL/6J mice brain.
Methods: Young healthy male C57BL/6J mice were injected intraperitoneally with MPTP at 80 mg/kg in two divided doses (2 x 40 mg/kg at 16h interval). TEL was administered one hour prior to first MPTP intoxication and thereafter once in two consecutive days. The animals were sacrificed 48 h after first MPTP injection and brains were collected for further analysis.
Results: TEL administration increased GSH content and decreased iNOS expression and NO level in MPTP intoxicated mice brains. Histopathological evaluation revealed that TEL decreased the cytoplasmic vacuolation and nuclear pigmentation in striatal and substantial nigral regions of MPTP intoxicated mice brain. The neuroprotective effect of TEL was further evidenced with increased neuronal nuclei (NeuN) immune fluorescence in MPTP mice brains.
Conclusion: The present study showed that TEL exerts neuroprotection by suppressing nitric oxide induced oxidative stress and the dopaminergic degeneration. The above findings suggests that TEL may act as a potential target in the management of PD.
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