Effects of Resveratrol on Anxiety-Like Behavior, Neuronal Damage, and Apoptotic Signaling in Female Rats Exposed to Methylparaben.

Methylparaben (MEP), a widespread preservative, raises neurotoxicity concerns through oxidative stress and inflammation. Resveratrol (RES) is a natural polyphenol with antioxidant and anti-inflammatory properties. This study investigated whether RES protects against MEP-induced neurotoxicity in female rats. Female Wistar rats were divided into five groups (n=10/group): control, vehicle (5% DMSO), MEP alone (200 mg/kg, s.c., 15 days), RES alone (20 mg/kg, i.p., 15 days), and MEP+RES co-treatment. We evaluated anxiety-like behavior (elevated plus maze), brain histopathology (cortex/hippocampus), oxidative stress markers (GSH, SOD), stress-related gene expression (Nrf2, ASK1, PP-1cs, PP-2Acs by qPCR), inflammatory proteins (TNF-α, IL-6 by immunohistochemistry), and apoptotic markers (BAX, BCL-2). MEP exposure significantly increased anxiety-like behavior, caused structural damage in cortex and hippocampus, depleted GSH and SOD, upregulated Nrf2, ASK1, PP-1cs, and PP-2Acs, elevated TNF-α, IL-6, and pro-apoptotic BAX, while reducing BCL-2. RES alone caused no adverse effects. Remarkably, RES co-administration significantly attenuated and partially restored MEP-induced alterations, restoring behavior, tissue architecture, antioxidant defenses, gene expression, and immune balance. RES effectively attenuates MEP-induced neurotoxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, positioning it as a promising neuroprotective agent against environmental toxicants.