Acrylamide-Induced Developmental and Molecular Toxicity in Drosophila melanogaster: The Role of Vanillic Acid in CncC/Keap1 Modulation

Abstract

Acrylamide, a chemical used in industrial applications, has been classified as an environmental toxin owing to its widespread contamination of drinking water and groundwater resources. Vanillic acid (VA) is a phenolic compound naturally occurring in numerous dietary sources and medicinal plants. VA exhibits a wide range of pharmacological properties, including antioxidant, anti-inflammatory, and neuroprotective activities. This study investigated the protective effects of VA against acrylamide-induced oxidative stress in Drosophila melanogaster at developmental, biochemical, and molecular levels. D. melanogaster were exposed to acrylamide (2 mM) alone or with VA at three doses (0.1, 0.5, and 1 mg/L). Acrylamide exposure elevated reactive oxygen species and lipid peroxidation, decreased antioxidant enzyme activities (SOD, CAT) and glutathione (GSH) levels, increased DNA damage by the Comet assay, upregulated mRNA expression of stress-related genes (SOD, CAT, gclc and hsp70) and detoxification-pathway components (Keap1 and CncC/Nrf2), and adversely affected developmental parameters (larval toxicity, crawling, climbing, survival, food intake, body weight and length). Co-administration of VA dose-dependently reduced lipid peroxidation and ameliorated antioxidant enzyme activities and DNA damage. VA also modulated the impaired developmental parameters of acrylamide-exposed larvae. These findings indicate that VA possesses considerable protective potential against acrylamide toxicity, with important implications for environmental and human health.