Unmasking the cytoskeletal collapse: a multi-organ investigation of arsenic trioxide-induced neuro-hepato-renal deterioration and expression of GFAP, CK-7, and Vimentin in Cirrhinus mrigala

Background The ubiquitous contamination of freshwater ecosystems by arsenic represents a critical ecotoxicological challenge and molecular perturbations in aquatic biota. Among inorganic arsenicals, arsenic trioxide (As₂O₃) exhibits high solubility and bioavailability, causes oxidative stress, cytotoxicity, and increases multi-organ dysfunction. The present study investigated the histopathological and immunohistochemical sequelae of sublethal arsenic trioxide exposure (3.75 mg/L; 1/8th of the 96-h LC₅₀ value of 30 mg/L) in Cirrhinus mrigala , a prominent sentinel teleost model, which were subjected to an exposure period (1, 10, 20, 30, and 40 days) and a control group. To characterize the neuro-hepato-renal axis, tissues were harvested and subjected to H&E staining and high-resolution immunohistochemical profiling for GFAP, CK-7, and Vimentin, respectively. Results Assessment of tissue architecture revealed duration-dependent progression. Neural tissues exhibited advanced neuronal degeneration, gliosis, spongiosis, and focal haemorrhaging. Hepatic architecture was characterized by hepatocellular vacuolation, coagulative necrosis, sinusoidal dilation, and microvesicular lipid accumulation. Renal impairments included significant glomerular atrophy, tubular degeneration, and vascular injury. Quantitative densitometric analysis of 3,3’-Diaminobenzidine (DAB) immunoreactivity using ImageJ demonstrated a significant, time-dependent upregulation of GFAP, CK-7, and Vimentin. Conclusions These findings indicate that coordinated cytoarchitectural degradation occurs across the neuro-hepato-renal axis, posing a critical threat to freshwater biodiversity and human health. The present study characterizes the modulation of GFAP, CK-7, and Vimentin in response to systemic arsenic-induced toxicity in Cirrhinus mrigala . By integrating these specific immunophenotypic markers, this research offers significant mechanistic insights into the environmental pathophysiology of arsenicosis in teleost species.