Monoisoamyl 2,3-dimercaptosuccinic acid attenuates arsenic induced toxicity: Behavioral and neurochemical approach

• Chronic exposure to arsenic (As) decreased behavioral activities in rats.
• As exposure resulted in mitochondrial oxidative damage with concomitant increase in MDA levels of brain regions.
• Alterations were more pronounced in cortex compared to cerebellum and hippocampus.
• Chelation therapy with MiADMSA reversed the arsenic toxicity by reducing the alterations in antioxidant enzymes.
• MiADMSA significantly reversed the As-induced oxidative injury and behavioral perturbations.

Chronic exposure to arsenic in drinking water is associated with skin lesions, neurological effects, hypertension and high risk of cancer. The treatment in use at present employs administration of thiol chelators, such as meso-2,3-dimercaptosuccinic acid (DMSA) which are compromised with number of limitations due to their lipophobic nature. To address this problem, therapeutic efficacy of monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), an analog of DMSA having lipophilic character, was examined against chronic arsenic poisoning in rats. Adult male Wistar rats were orally exposed to arsenic (2 mg sodium arsenite/kg body weight) for 10 weeks followed by treatment with MiADMSA (50 mg/kg, orally, once daily for 5 consecutive days). As-exposed rats showed significant differences in behavioral functions (open field behavior, total locomotor activity, grip strength and exploratory behavior) and water maze learning. Further, the biochemical studies performed on three brain regions (cerebellum, cortex and hippocampus) also showed significant elevation in malondialdehyde (MDA) levels with a concomitant decrease in the oxidative stress marker enzymes Mn-superoxide dismutase (Mn-SOD), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST). The alterations were more pronounced in cortex compared to cerebellum and hippocampus. The results showed that MiADMSA significantly reversed the As-induced alterations in behavior and biochemical variables suggestive of oxidative injury.