Title:Protective Effect of Monoisoamyl-2, 3-Dimercaptosuccinic Acid against Manganese-induced Neurotoxicity in Rats
Volume: 21
Issue: 3
Author(s): Awanish Mishra*, Anjali Dahia and Amit Jaiswal
Affiliation:
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli (NIPER-R), Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow (UP)- 226002,India
Keywords:
Manganese, neurotoxicity, chelation therapy, heavy metal, MiADMSA, protective effect.
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.
