Histochemical and Semi-Quantitative Evidence of Dimoxystrobin-Induced Liver Extracellular Matrix Remodelling in Adult...

Strobilurin fungicides are among the most widely used agrochemicals worldwide. Dimoxystrobin has been shown to induce hepatic injury in adult zebrafish; however, whether this damage also involves early extracellular matrix remodelling and hepatobiliary remodelling remains unknown. Here, we investigated early remodelling of the extracellular matrix, focusing on initial collagen deposition and glycosaminoglycan redistribution after a short-term exposure (96 h) to two environmentally relevant concentrations of dimoxystrobin (6.56 and 13.13 µg/L) on the liver of Danio rerio using an integrated histological, histochemical, and semi-quantitative approach. The results showed a progressive dose-dependent alteration of hepatic architecture, accompanied by a significant increase in bile pigment-like deposits and collagen deposition. Exposure also induced a significant increase in the deposition of acidic glycosaminoglycans and a severe depletion of glycogen-dependent Periodic Acid-Schiff positivity components, accompanied by an increase in amylase-resistant Periodic Acid-Schiff reactive components. Overall, these findings indicate that dimoxystrobin-induced hepatotoxicity extends beyond parenchymal degeneration to encompass coordinated stromal and hepatobiliary remodelling. The present study also indicates that the periductal microenvironment may represent a sensitive target of dimoxystrobin toxicity and supports the use of histochemical and semi-quantitative analyses as sensitive tools for detecting sublethal pesticide-induced early extracellular matrix remodelling in fish liver.