Vanillic acid ameliorates diethyl phthalate and bisphenol S‐induced oxidative stress and neuroinflammation in the hippocampus of experimental rats

Abstract

Abstract Long‐term adverse effects on human health are caused by exogenous compounds that alter the functions of biological systems, especially neuroendocrine disruptors like diethyl phthalate (DEP) and bisphenol S (BPS). Although vanillic acid (VA) has pertinent neuropharmacological characteristics, its effect against DEP + BPS‐induced neurotoxicity has not been explored. This study proposed that VA may offer protection against the neurotoxicity caused by DEP + BPS. Thirty male Wistar rats were randomly distributed across five groups: a control group receiving DMSO, a group exposed to a mixture of BPS and DEP, two BPS + DEP‐exposed groups treated with VA at doses of 25 mg/kg or 50 mg/kg, and a nonexposed group treated with 50 mg VA/kg. After 21 days, the hippocampal tissues were processed for biochemical analyses. Our results indicate that exposure to DEP + BPS upregulated neurosignaling mediators (NTPDase, ADA, MAO‐A, and Ca 2+ ), inhibited others (AChE and Ca 2+ /Mg 2+ ‐ATPase), decreased hippocampus antioxidants (GSH, GPx, CAT, and SOD), and elevated markers of oxidative stress/damage (NO, H 2 O 2 , MDA, and AOPP). AR, BAX, TNF‐α, BAK1, and IL‐1β expressions were upregulated, while IL‐10 and BDNF expressions were downregulated. NF‐κB and caspase‐3/9 pathways were also upregulated. Co‐treatment with vanillic acid remarkably precluded these neurotoxic outcomes by improving neurosignaling, augmenting antioxidant status, abrogating oxidative damage, inflammation (TNF‐α, IL‐1β), and apoptosis (BAX, BAK1, caspase‐3/9). Vanillic acid also restored IL‐10 and BDNF levels, thereby exhibiting neuroprotective effects, corroborated by histological examinations. We posit vanillic acid as a safe and effective therapeutic agent against neurotoxicity occasioned by exposure to neuroendocrine disruptors.