Alpha Lipoic Acid and Monoisoamyl-DMSA Combined Treatment Ameliorates Copper-Induced Neurobehavioral Deficits, Oxidative Stress, and Inflammation

Abstract

Copper (Cu), being an essential trace metal, plays several roles in biological processes, though exposure to Cu can be potentially toxic to the brain and a few other soft organs. In the present study, we investigated the effects of the combined administration of monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA), which is a new chelator, and alpha lipoic acid (ALA) and an antioxidant that is made naturally in the body and is also found in foods, against Cu-induced oxidative stress in rats. Rats were exposed to 20 mg/kg copper sulfate for 16 weeks once a day via the oral route. After 16 weeks of exposure, animals were divided into different sub-groups. Group I was divided into three subgroups: Group IA, control; Group IB, MiADMSA (75 mg/kg, oral); Group IC, ALA (75 mg/kg, oral), while Group II was divided into four subgroups: Group IIA, Cu pre-exposed; Group IIB, Cu+ MiADMSA; Group IIC, Cu+ ALA; Group IID, Cu+ ALA+ MiADMSA. Exposure to Cu led to significant neurobehavioral abnormalities; treatment with MiADMSA, and in particular MiADMSA + ALA, significantly ameliorated the neurobehavioral parameters and restored the memory deficits in rats. Oxidative stress variables (ROS, nitrite, TBARS, SOD, catalase) and inflammatory markers (TNF-α, and IL-1β), which were altered on Cu exposed rats, also responded favorably to ALA+ MiADMSA combined treatment. Thus, combined administration of MiADMSA and ALA might be a better treatment strategy than monotherapy with MiADMSA or ALA against Cu-induced neurotoxicity, particularly in reducing oxidative stress, neurobehavioral abnormalities, and inflammatory markers.