Ommati Mohammad Mehdi, Heidari Reza, Ghanbarinejad Vahid, Aminian Ahmadreza, Abdoli Narges, Niknahad Hossein
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Bioinformatics, College of Life Sciences, Shanxi Agricultural University, Taigu, Peoples' Republic of China.
Nutr Neurosci. 2020 Sep;23(9):731-743. doi: 10.1080/1028415X.2018.1552399. Epub 2019 Mar 11.
: 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. 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. 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. 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.
锰（Mn）是一种必需的微量元素，在生理上参与多种重要酶的结构组成。尽管它必不可少，但过量接触锰具有毒性，脑组织是主要的靶器官。目前尚无针对锰神经毒性的特异性且临床可用的治疗/预防方法。肌肽是一种具有多种生理作用的神经肽。该肽的神经保护特性已在不同实验模型中得到评估。本研究旨在探讨补充肌肽在锰诱导的神经毒性动物模型中的作用及其潜在作用机制。雄性C57BL/6小鼠单独接受锰（100 mg/kg，皮下注射）和/或与肌肽（10、50和100 mg/kg，腹腔注射）联合使用。监测了多个运动活动指标。此外，还评估了锰暴露动物脑组织中的氧化应激生物标志物和线粒体功能。锰暴露动物出现了明显的运动功能障碍。此外，锰处理动物脑组织中的氧化应激生物标志物显著增加，线粒体功能指标受损。研究发现，补充肌肽（10、50和100 mg/kg，腹腔注射）可减轻锰诱导的运动缺陷。此外，在锰中毒动物模型中，该肽减轻了氧化应激生物标志物，并保留了脑组织线粒体功能。这些数据表明，肌肽是一种潜在的抗锰神经毒性神经保护剂。肌肽的抗氧化和线粒体保护作用可能在其抗锰毒性的神经保护特性中起重要作用。
