Asiatic Acid Ameliorates Chlorpyrifos-Induced Toxicity in Rats: Biochemical and Histopathological Insights
TL;DR
This study provides the first demonstration that asiatic acid exerts robust systemic antioxidative, hepatoprotective, and neuroprotective effects against CPF-induced toxicity, highlighting AA’s therapeutic potential for mitigating organophosphate pesticide poisoning.
Abstract
ABSTRACT Introduction: Chlorpyrifos (CPF), one of the most widely used organophosphorus (OP) insecticides, exerts its toxic effects in part by inducing oxidative stress. Despite increasing recognition of natural antioxidants as potential countermeasures, the efficacy of asiatic acid (AA), a bioactive triterpenoid from Centella asiatica, against CPF-induced toxicity remains unexplored. This study aimed to investigate the protective effects of AA against CPF-incuded toxicity model in rats by analyzing biochemical and histological parameters in serum, liver, and brain tissues. Material and Methods: Adult male Sprague Dawley rats (n=30) were randomly divided into five groups: control, CPF (279 mg/kg, subcutaneously), and three AA-pretreated groups (35, 70, and 140 mg/kg, per os) for 14 days prior to CPF exposure. Oxidative stress markers [malondialdehyde (MDA), advanced oxidation protein products (AOPP)] and antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)] were measured in serum, liver, and brain. Histopathological and immunohistochemical analyses assessed tissue injury and apoptotic responses. Results: AA administration significantly attenuated CPF-induced oxidative damage and restored antioxidant defenses in a dose-dependent manner. Histopathological analyses confirmed that AA mitigated hepatic and neuronal damage and preserved tissue architecture. Immunohistochemistry revealed that AA suppressed CPF-induced upregulation of the pro-apoptotic protein Bcl-2-associated X protein (Bax), indicating reduced apoptosis. Conclusion: This study provides the first demonstration that AA exerts robust systemic antioxidative, hepatoprotective, and neuroprotective effects against CPF-induced toxicity. These findings highlight AA’s therapeutic potential for mitigating organophosphate pesticide poisoning, warranting further translational research. Keywords: Asiatic acid, chlorpyrifos, hepatoprotection, neuroprotection, organophosphate toxicity, oxidative stress