Temperature amplifies cadmium toxicity through bioaccumulation dynamics and hepatic cellular responses in Danio rerio

Elevated environmental temperatures associated with climate change may potentiate heavy metal toxicity in aquatic ecosystems, yet the mechanisms underlying this interaction remain poorly characterized. This study elucidates how temperature modulates cadmium (Cd) bioaccumulation kinetics and subsequent cellular pathophysiology in adult zebrafish ( Danio rerio ) during chronic exposure (21 days) at control (26°C) versus elevated (34°C) temperatures. Tissue-specific analysis revealed pronounced hepatic Cd accumulation that was significantly amplified (2.4-fold increase) at 34°C compared to 26°C. This temperature-dependent bioaccumulation pattern corresponded with differential metallothionein induction profiles. Histopathological assessment documented progressive hepatocellular deterioration characterized by cytoplasmic vacuolation, sinusoidal dilation, and leukocyte infiltration—effects exacerbated at elevated temperature. Comprehensive biochemical profiling demonstrated marked dysregulation of glucose homeostasis, protein metabolism, lipid parameters, and calcium regulation, with temperature-dependent perturbation patterns. Mechanistic investigations revealed that high temperature synergistically enhanced Cd-induced oxidative stress, evidenced by elevated reactive oxygen species generation, lipid peroxidation, and compensatory antioxidant enzyme modulation. Flow cytometric analysis using Annexin V-FITC/PI and JC-1 staining confirmed that temperature amplified Cd-induced hepatocyte apoptosis through mitochondria-dependent pathways. These findings establish temperature as a critical determinant of Cd toxicokinetics and toxicodynamics in fish, with important implications for ecological risk assessment in thermally fluctuating aquatic environments under climate change scenarios.