Ecotoxicological of Emerging Pharmaceuticals on African Catfish ( <i>Clarias gariepinus</i> ): Biomarkers for Neurotoxicity, Immunotoxicity, and Histopathology

Pharmaceutical residues have emerged as critical emerging contaminants, posing substantial threats to aquatic biodiversity and sustainable aquaculture. However, their sublethal effects on nontarget aquatic species remain underexplored. This study evaluates the comparative toxicity of three widely detected pharmaceuticals: gabapentin (GPT, anticonvulsant), valsartan (VAL, antihypertensive), and codeine (COD, opioid analgesic)—on African catfish ( Clarias gariepinus ), a species of ecological and aquacultural importance. Fish were exposed for 15 days to environmentally relevant concentrations of GPT (79.86 µg/L), VAL (28.22 µg/L), and COD (5.27 µg/L). Neurotoxicity was assessed via acetylcholinesterase (AChE), monoamine oxidase (MAO), and cortisol levels; immunotoxicity was evaluated through lysozyme (LZM) activity, immunoglobulin M (IgM), and phagocytic activity (PA), while histopathological and histochemical changes were examined in the kidney, intestine, and spleen. All pharmaceutical exposures induced significant neuroendocrine and immune disruptions. AChE activity was reduced, while MAO and cortisol levels increased, indicating neurotoxic stress. Immunosuppression was evidenced by decreased LZM, IgM, and PA. Histological examination revealed tissue degeneration, mucosal damage, and lymphoid depletion, with PAS staining showing glycogen depletion across all treated groups. Among the tested compounds, VAL induced the most severe multisystemic effects, followed by GPT and COD. These findings highlight the overlooked ecological risks of pharmaceutical pollutants, underlining their potential to compromise fish health, disrupt aquaculture productivity, and threaten aquatic biodiversity even at low environmental concentrations.