Potent neuroprotective and antioxidant activity of apomorphine in MPTP and 6-hydroxydopamine induced neurotoxicity
Apomorphine is a potent radical scavenger and iron chelator. In vitro apomorphine acts as a potent iron chelator and radical scavenger with IC50 of 0.3 μM for iron (2.5 μM) induced lipid peroxidation in rat brain mitochondrial preparation, and it inhibits mice striatal MAO-A and MAO-B activities with IC50 values of 93 μM and 241 μM. Apomorphine (1–10 μM) protects rat pheochromocytoma (PC12) cells from 6-hydroxydopamine (150 μM) and H2O2 (0.6 mM) induced cytotoxicity and cell death. The neuroprotective property of (R)-apomorphine, a dopamine D1-D2 receptor agonist, has been studied in the MPTP (N-methyl-4-pheny1-1, 2,3,6-tetrahydropyridine) model of Parkinson’s disease. (R)-apomorphine (5–10mg/kg, s.c.) pretreatment in C57BL mice, protects against MPTP (24mg/kg, I.P) induced loss of nigro-striatal dopamine neurons, as indicated by striatal dopamine content, tyrosine hydroxylase content and tyrosine hydroxylase activity. It is suggested that the neuroprotective effect of (R)-apomorphine against MPTP neurotoxicity derives from its radical scavenging and MAO inhibitory actions and not from its agonistic activity, since the mechanism of MPTP dopaminergic neurotoxicity involves the generation of oxygen radical species induced-oxidative stress.
KeywordsTyrosine Hydroxylase Iron Chelator MPTP Treatment MPTP Treated Mouse PC12 Cell Culture
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