Protective Effect of Monoisoamyl-2, 3-Dimercaptosuccinic Acid against Manganese-induced Neurotoxicity in Rats

Abstract

Background: Apart from being an essential heavy metal, Manganese (Mn) serves as an important component of the antioxidant enzyme system in humans. Overexposure to manganese leads to the development of manganism, which is characterized by motor dysfunction along with neurodegeneration. The management of manganism often utilizes chelation therapy. In this regard, Monoisoamyl-2, 3-Dimercaptosuccinic Acid (MiADMSA) has been reported as a novel arsenic chelator, due to the presence of vicinal sulfhydril group. MiADMSA has been reported to reduce the level in divalent ions (like copper) therefore, it may be hypothesized that MiADMSA would be helpful in Mn-induced neurotoxicity.

Objective: This study is envisaged to explore the protective effect of MiADMSA on Mn-induced neurotoxicity.

Methods: Mn exposure was carried out by intraperitoneal administration of Mn (as manganese chloride, 10 mg/kg; i.p.). The animals were treated with MiADMSA (50 mg/kg; p.o.) either alone or in combination with Mn. The effect of different treatments on neurobehavioral functions was observed by assessing spontaneous locomotor activity, motor rotarod test, and depression-like behavior in the forced swim test. After behavioral evaluations, all the animals were sacrificed and the brain and liver were isolated for metal estimations.

Results: Mn exposure leads to loss of motor coordination as observed in spontaneous locomotor activity and rotarod test. However, treatment with MiADMSA significantly improved motor impairments as compared to Mn exposed animals. Accumulation of Mn in the liver and brain has been recorded with Mn exposure; however, MiADMSA treatment significantly reduced the Mn content from the liver and brain.

Conclusion: The outcome of the study suggests that treatment with MiADMSA reversed Mn-induced neurotoxicity by reducing Mn load. Therefore, the use of MiADMSA may be suggested in manganese toxicity, after careful investigation.

Keywords: Manganese; MiADMSA; chelation therapy; heavy metal; neurotoxicity; protective effect..