Carnosine Mitigates Manganese Mitotoxicity in an In Vitro Model of Isolated Brain Mitochondria

Abstract

Purpose: Manganese (Mn) is a neurotoxic chemical which induces a wide range of complications in the brain tissue. Impaired locomotor activity and cognitive dysfunction are associated with high brain Mn content. At the cellular level, mitochondria are potential targets for Mn toxicity. Carnosine is a dipeptide abundantly found in human brain. Several pharmacological properties including mitochondrial protecting and antioxidative effects have been attributed to carnosine. The current study aimed to evaluate the effect of carnosine treatment on Mn-induced mitochondrial dysfunction in isolated brain mitochondria. Methods: Mice brain mitochondria were isolated based on the differential centrifugation method and exposed to increasing concentrations of Mn (10 µM-10 mM). Carnosine (1 mM) was added as the protective agent. Mitochondrial indices including mitochondrial depolarization, reactive oxygen species (ROS) formation, mitochondrial dehydrogenases activity, ATP content, and mitochondrial swelling and permeabilization were assessed. Results: Significant deterioration in mitochondrial indices were evident in Mn-exposed brain mitochondria. On the other hand, it was found that carnosine (1 mM) treatment efficiently prevented Mn-induced mitochondrial impairment. Conclusion: These data propose mitochondrial protection as a fundamental mechanism for the effects of carnosine against Mn toxicity. Hence, this peptide might be applicable against Mn neurotoxicity with different etiologies (e.g., in cirrhotic patients).

Cellular and mitochondrial taurine depletion in bile duct ligated rats: a justification for taurine supplementation in cholestasis/cirrhosis

“…Also, mitochondrial injury seems to play a crucial role in the pathogenesis of these complications [139]. All bile constituents such as Mn, bilirubin, and bile acids have adverse effects on mitochondrial function and energy metabolism [139,145,146]. In the current study, we discovered a significant decline in the TAU content of the brain tissue and isolated mitochondria (Figs.…”

Covid-19, Carnosine and Cognition

“…27 The dipeptide has also been shown to inhibit growth of transformed cells. 28 Metabolic effects such as partial inhibition of glycolysis, 29 and enhancement of mitochondrial activity 30 and proteolysis 31 have also been detected. Carnosine has also been shown to delay senescence in cultured human fibroblasts and to rejuvenate senescent cells.…”

Carnosine Mitigates Biomarkers of Oxidative Stress, Improves Mitochondrial Function, and Alleviates Histopathological Alterations in the Renal Tissue of Cholestatic Rats

“…103,104 Previously, we found that administration of high doses of CAR had no significant adverse effects in critically ill rats (Cirrhotic rats), but also protects the liver tissue. 40,52,97,103 Hence, this peptide could be readily administered in human cases of CN.…”

“…It has been found that CAR administration significantly enhanced ATP production and mitigated mitochondria-mediated cell death in different experimental models. [39][40][41][42][43][44][45] All these properties make CAR as a potential candidate for the management of CN complications. The current study aimed to assess the effects of CAR administration against cholestasis-induced renal injury.…”