The cascade of cadmium toxicity: from cellular damage to pyroptotic responses in fish Channa punctatus.

Cadmium pollution is a major environmental issue threatening aquatic ecosystems and the health of aquatic organisms. Our study examines cadmium toxicity at different levels, highlighting pyroptotic cell death in the freshwater fish Channa punctatus (spotted snakehead). For this purpose, 90 well-acclimatized fish were categorized into three groups: one control and two treatment groups, i.e., T1 and T2, which were exposed to two sub-lethal concentrations of cadmium chloride (Cdcl₂), i.e., 1.18 mg/L (one-tenth of 96-h lethal concentration [LC₅₀]) and 2.36 mg/L (one-fifth of 96-h LC₅₀), respectively, for a duration of 7, 14, and 21 days. Post-completion of experimental periods, various assessments were carried out. Reactive oxygen species levels significantly increased, indicating enhanced oxidative stress, along with elevated activities of superoxide dismutase and catalase (P < 0.05). In contrast, reduced glutathione levels decreased in a dose- and duration-dependent manner (P < 0.05). Additionally, lipid peroxidation increased markedly, and liver biomarkers, including serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and lactate dehydrogenase, were significantly elevated (P < 0.05) in a time- and concentration-dependent pattern. Histopathological investigations of liver revealed pronounced deformities that were dose-dependent, with higher concentrations of cadmium causing more severe damage. Subsequently, prolonged cadmium exposure led to pyroptosis in the hepatocytes, characterized by the elevated expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; caspase-1, interleukin-1β, interleukin-18; apoptosis-associated speck-like protein containing a CARD; and Gasdermin E. These results highlighted the significant impact of cadmium on C. punctatus, underscoring its importance as a key bio-indicator for aquatic pollution. The study emphasizes the urgent need to monitor and regulate cadmium levels to protect aquatic life and maintain ecological balance.