The neuroprotective properties of carnosine in a mouse model of manganism is mediated via mitochondria regulating and antioxidative mechanisms

ABSTRACT

Objective(s): Manganese (Mn) is an essential trace element physiologically incorporated in the structure of several vital enzymes. Despite its essentiality, excessive Mn exposure is toxic with brain tissue as the primary target organ. There is no specific and clinically available therapeutic/preventive option against Mn neurotoxicity. Carnosine is a neuropeptide with several physiological roles. The neuroprotective properties of this peptide have been evaluated in different experimental models. The current study was designed to investigate the effect of carnosine supplementation and its potential mechanisms of action in an animal model of Mn-induced neurotoxicity. Materials and Methods: Male C57BL/6 mice received Mn (100 mg/kg, s.c) alone and/or in combination with carnosine (10, 50, and 100 mg/kg, i.p). Several locomotor activity indices were monitored. Moreover, biomarkers of oxidative stress and mitochondrial function were assessed in the brain tissue of Mn-exposed animals. Results: Significant locomotor dysfunction was revealed in Mn-exposed animals. Furthermore, brain tissue biomarkers of oxidative stress were significantly increased, and mitochondrial indices of functionality were impaired in Mn-treated animals. It was found that carnosine supplementation (10, 50, and 100 mg/kg, i.p) alleviated the Mn-induced locomotor deficit. Moreover, this peptide mitigated oxidative stress biomarkers and preserved brain tissue mitochondrial functionality in the animal model of manganism. Conclusion: These data indicate that carnosine is a potential neuroprotective agent against Mn neurotoxicity. Antioxidative and mitochondria protecting effects of carnosine might play a fundamental role in its neuroprotective properties against Mn toxicity.

KEYWORDS:

• Manganism
• bioenergetics
• dopaminergic system
• locomotor dysfunction

Acknowledgements

The authors gratefully acknowledged technical and financial support by Pharmaceutical Sciences Research Center and Vice Chancellor of Research Office of Shiraz University of Medical Sciences (Grant number 14210/13477).

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Dr Mohammad Mehdi Ommati obtained his Ph.D. in Animals Physiology from Shiraz University, Shiraz, Iran. Currently, he is the assistant professor in the Department of Bioinformatics, College of life Sciences, Shanxi Agricultural University, Taigu, China.

Dr Reza Heidari obtained his Pharm.D. degree from Shiraz University of Medical Sciences in September 2009. He obtained his Ph.D. in Toxicology from Tabriz University of Medical Sciences in December 2013. Dr Heidari is now the assistant professor of Toxicology in Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences.

Mr Vahid Ghanbarinejad is a toxicology Ph.D. student at the Department of Pharmacology and Toxicology, Shiraz University of Medical Sciences.

Mr Ahmadreza Aminian is a Pharm.D. student at the School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Dr Narges Abdoli holds a Pharm.D. degree and Pharmacology Ph.D. Currently, she works at Iran Food and Drug Administration, Ministry of Health, Tehran, Iran.

Proffessor Hossein Niknahad holds a Pharm.D. degree and Toxicology Ph.D. He is Professor of Toxicology at the Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Additional information

Funding

The authors gratefully acknowledged technical and financial support by Pharmaceutical Sciences Research Center and Vice Chancellor of Research Office of Shiraz University of Medical Sciences [grant number 14210/13477].