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

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 Ca2+), inhibited others (AChE and Ca2+/Mg2+-ATPase), decreased hippocampus antioxidants (GSH, GPx, CAT, and SOD), and elevated markers of oxidative stress/damage (NO, H2O2, 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.