Mohammad Mehdi Ommati1,2, Reza Heidari1, Vahid Ghanbarinejad1,3, Ahmadreza Aminian1,3, Narges Abdoli4, Hossein Niknahad1,3. 1. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Department of Bioinformatics, College of Life Sciences, Shanxi Agricultural University, Taigu, Peoples' Republic of China. 3. Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. 4. Iran Food and Drug Administration (IFDA), Ministry of Health, Tehran, Iran.
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.
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.