Effects of catechin on a rodent model of autism spectrum disorder: implications for the role of nitric oxide in neuroinflammatory pathway.

Abstract

AIM\nThe present research work aims at deciphering the involvement of nitric oxide pathway and its modulation by (\u2009±)catechin hydrate in experimental paradigm of autism spectrum disorders (ASD).\n\n\nMETHOD\nAn intracerebroventricular infusion of 4\xa0μl of 1\xa0M propanoic acid was given in the anterior region of the lateral ventricle to induce autism-like phenotype in male rats. Oral administration of (\u2009±)catechin hydrate (25, 50, and 100\xa0mg/kg) was initiated from the 3rd day lasting till the 28th day. L-NAME (50\xa0mg/kg) and L-arginine (800\xa0mg/kg) were also given individually as well as in combination to explore the ability of (\u2009±)catechin hydrate to act via nitric oxide pathway. Behavior test for sociability, stereotypy, anxiety, depression, and novelty, repetitive, and perseverative behavior was carried out between the 14th and 28th day. On the 29th day, animals were sacrificed, and levels of mitochondrial complexes and oxidative stress parameters were evaluated. We also estimated the levels of neuroinflammatory and apoptotic markers such as TNF-α, IL-6, NF-κB, IFN-γ, HSP-70, and caspase-3. To evaluate the involvement of nitric oxide pathway, the levels of iNOS and homocysteine were estimated.\n\n\nRESULTS\nTreatment with (\u2009±)catechin hydrate significantly ameliorated behavioral, biochemical, neurological, and molecular deficits. Hence, (\u2009±)catechin hydrate has potential to be used as neurotherapeutic agent in ASD targeting nitric oxide pathway-mediated oxidative and nitrosative stress responsible for behavioral, biochemical, and molecular alterations via modulating nitric oxide pathway.\n\n\nCONCLUSION\nThe evaluation of the levels of iNOS and homocysteine conclusively establishes the role of nitric oxide pathway in causing behavioral, biochemical, and molecular deficits and the beneficial effect of (\u2009±)catechin hydrate in restoring these alterations.