Synthetic azo-dye, Tartrazine induces neurodevelopmental toxicity via mitochondria-mediated apoptosis in zebrafish embryos

Tartrazine (TZ), or E 102 or C Yellow, is a commonly used azo dye in the food and dyeing industries. Its excessive usage beyond permissible levels threatens human health and the aquatic environment. While previous studies have reported adverse effects such as mutagenicity, carcinogenicity, and reproductive toxicity. Our study aimed to comprehensively evaluate the developmental neurotoxicity of TZ exposure via biochemical and behavioral examinations and explored the underlying mechanism via gene expression analyses. TZ at an environmentally relevant concentration (50 mg/L) significantly induces oxidative stress, altered antioxidant (SOD, CAT and GSH) response, triggered cellular damage (MDA and LDH), and induced neuro-biochemical changes (AChE and NO). Gene expression analyses revealed broad disruptions in genes associated with antioxidant defense (sod1, cat, and gstp1), mitochondrial dysfunction (mfn2, opa1, and fis1),evoked inflammatory response (nfkb, tnfa, and il1b), apoptosis activation (bcl2, bax, and p53), and neural development (bdnf, mbp, and syn2a). Behavioral analysis indicated altered thigmotaxis, touch response, and locomotion depending on the concentration of TZ exposure. Remarkably, the observed effective concentrations were consistent with the permitted levels in food products, highlighting the neurodevelopmental effects of TZ at environmentally relevant concentrations. These findings provide valuable insights into the underlying molecular mechanisms, particularly the role of mitochondriamediated apoptosis, contributing to TZ-induced neurodevelopmental disorders in vivo.