Neuroprotective Effects of Zinc on Redox Imbalance and Progesterone Levels in MPTP-Induced Parkinson's disease in Rats

Abstract

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons, oxidative stress, and disruptions in neurotransmitter and neuroactive steroid homeostasis. Aim: This study evaluated the neuroprotective efficacy of intranasal zinc pretreatment on oxidative stress markers, serum progesterone concentrations, and behavioral phenotypes in a male Wistar rat model of PD induced by intranasal administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).  Methodology: Sixteen adult male Wister rats (190-240 g) were randomized into four groups (n = 4): Control (Saline), MPTP-treated (1mg/nostril/day), MPTP + Zinc-treated (Co-administered), and Zinc-treated (2 mg/ml). Treatments were administered intranasally for 7 days. Progesterone was assessed via competitive ELISA. Oxidative stress was evaluated through catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) assays. Result: MPTP caused a marked decrease in serum progesterone (p<0.0001 vs control) and antioxidant enzyme activities (SOD, GSH, CAT) with a concomitant rise in brain MDA (p<0.0001) compared to control rats. Zn pretreatment significantly attenuated these effects: progesterone levels were higher in MPTP+Zn compared to MPTP-only rats (p<0.01), and brain MDA was reduced (p<0.0001) compared to MPTP-only rats, with restored SOD, GSH and CAT activities (p<0.001) compared to MPTP-only rats. Total protein loss induced by MPTP was also ameliorated by Zn pretreatment (p<0.0001) compared to MPTP-only rats. Conclusion: These data indicate that zinc mitigates MPTP-induced redox imbalance and preserves progesterone levels. Our findings suggest intranasal Zn exerts neuroprotective effects in this PD model by bolstering antioxidant defenses and hormonal homeostasis.