Dietary watermelon (Citrullus lanatus) rind mitigates nickel- and copper-induced hepatic, metabolic, and nrf2/keap1 signaling disruptions in Nile tilapia (Oreochromis niloticus).

Rising nickel (Ni) and copper (Cu) pollution in water bodies has the potential to alter fish physiology and undermine aquaculture sustainability. A valuable byproduct, the watermelon rind (Citrullus lanatus), has potent antioxidant properties. However, its hepatoprotective role against Ni + Cu co-exposure in Nile tilapia (Oreochromis niloticus) remains uninvestigated. Hence, this study assessed the efficacy of dietary C. lanatus rind powder (CLRP) in safeguarding against liver damage induced by Ni + Cu. Fish (37.30 ± 0.20 g) were assigned to four groups: control, CLRP (40 g/kg diet), Ni + Cu (3.60 and 3.35 mg/L), and CLRP + Ni+Cu for 45 days. Findings showed hepatic dysfunction, as evidenced by increased liver enzymes and reduced protein fractions concurrent with Ni and Cu exposure. In addition, disruption of the lipid profile (increased triglycerides and cholesterol) and elevation of bilirubin fractions were evident in the Ni + Cu group. Simultaneous exposure to Ni and Cu induced suppression of antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), besides the elevation of malondialdehyde levels. Microscopic analysis of hepatic tissue showed hepatocyte necrosis and degeneration as well as dilation of the portal veins. Furthermore, the co-occurring exposure altered the antioxidant signaling pathway (nrf2/keap1). It also downregulated immune function genes (il10 and ctsb) and upregulated stress response genes (hsp70 and hsp90). Importantly, CLRP supplementation notably strengthens antioxidant capacity, supports lipid metabolism, and maintains liver architecture. Additionally, it reduces hepatocyte injury and transcriptional disruptions. Overall, CLRP (40 g/kg) shows promise in protecting Nile tilapia against Ni + Cu combined exposure, supporting its use as a feed additive in aquaculture.