Assessing cisplatin-induced acute toxicity in zebrafish (Danio rerio): a multi-organ perspective at realistic...

Cisplatin, a widely used platinum-based chemotherapeutic agent, has been detected in hospital effluents and wastewater treatment plant discharges, raising concerns about its potential ecological impact, particularly on aquatic organisms. Despite its significant presence in environmental matrices, limited studies have investigated the effects of cisplatin at concentrations within the lower range of those reported in wastewater treatment plant effluents (< 150 μg/L) on fish health. This study aimed to assess the impact of cisplatin (2, 5, 10 μg/L) on zebrafish (Danio rerio) by evaluating oxidative stress responses and gene expression alterations in critical organs, including the liver, brain, gut, and gills. Results indicated distinct tissue-specific oxidative stress responses, with high negative correlations between antioxidant enzymes (SOD and CAT) and oxidative biomarkers in the gut and gills. Gene expression analysis, on the other hand, revealed marked upregulation of apoptotic markers (bax, p53, casp3) and stress-related genes (nrf1, nrf2) across all tissues, indicating a robust apoptotic response at low concentrations. Moreover, the expression of mapk8, prkaa2, ddit3, and stim1a was significantly elevated in all organs, reflecting the activation of multiple pathways, including DNA damage, mitochondrial dysfunction, endoplasmic reticulum stress, and calcium dysregulation. The study concludes that cisplatin exposure adversely affects zebrafish health, emphasizing the urgency of assessing the environmental implications of this widely used chemotherapeutic agent.