Tiron alleviates MPTP‐induced Parkinsonism in mice via activation of Keap‐1/Nrf2 pathway. Issue 3 (28th December 2020)

• Record Type: Journal Article
• Authors: Mohamed, Shrook A.; El‐Kashef, Dalia H.; Nader, Manar A.
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 35:Issue 3(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-28
• Subjects: dopamine -- GABA -- HO‐1 -- Keap‐1/Nrf2 -- MPTP -- Tiron; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.22685
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: Parkinsonism is a neurodegenerative disease that is common all over the world. This study aimed at exploring the neuroprotective effect of tiron against 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP)‐induced Parkinsonism. MPTP (30 mg/kg, intraperitoneally [ip]) was injected in mice daily for 5 consecutive days. Mice were treated with tiron (140 and 280 mg/kg, ip) or levodopa (8.4 mg/kg, orally) for 10 consecutive days starting 5 days before MPTP injection. At the end of the experiment, behavioral tests were conducted to assess the neuroprotective effect of tiron. Moreover, oxidative stress was assessed via measuring antioxidant enzyme, such as catalase, and lipid peroxidation was evaluated as malondialdehyde. Neuronal damage was also detected by histopathological examination and via estimating hippocampal levels of dopamine, γ‐aminobutyric acid, and nuclear factor erythroid‐derived 2‐like 2. In addition, the expression of Kelch‐like ECH‐associated protein 1 and heme oxygenase‐1 was assessed by immunohistochemistry. Compared with the blank control group and the positive control group, the inhibitory effect of tiron on MPTP‐induced neurodegenerative injury was statistically significant. Abstract : Highlights: Tiron exerts neuroprotective effects against 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine‐induced Parkinsonism. Tiron improves behavioral and locomotor function of Parkisonian mice. Tiron restores normal levels of dopamine and γ‐aminobutyric acid in the hippocampus of Parkisonian mice. Tiron activates Kelch‐like ECH‐associated protein 1/nuclear factor erythroid‐derived 2‐like 2 pathway. Tiron possesses antioxidant properties.