Apoptogenic, necrogenic and varied patho-morphological changes associated with diverse hepatotoxins.

摘要

Histopathology plays a critical role in the diagnosis of drug-induced liver disease. Evaluation of liver biopsy for adverse drug reaction is one of the most challenging problems in the liver pathology. The diagnosis of drug-induced liver disease is an intriguing question often accompanied by insufficient clinical data and the difficulty of interpreting exposure to drugs, toxins and other chemical agents. This study investigated the patho-morphological changes induced by several classic hepatotoxins such as Furosemide (Fur), Streptozotocin (Stz), Dimethylnitrosamine (DMN), Carbon tetrachloride (CC14) and Doxorubicin (Dox) on H& E/PAS stained mouse liver sections. These bioactivation dependent liver toxins are potential inducers of free radicals and biologically reactive intermediates. This study was an attempt to characterize multiple pathological lesions induced by such hepatotoxins and to investigate overlapping of such varied morphological features. In this study, Fur revealed massive sinusoidal dialatation, severe centrilobular necrosis, excessive vacuolization and apoptotic morphology. Stz, a pancreatic 13-cell specific toxin, showed conspicuous hepatocellular damage in the form of microvesicular steatosis, ballooning degeneration and formation of ground glass hepatocytes. DMN, a potent carcinogen and mutagen, is an established inducer of apoptosis. This study highlighted DMN-induced macrovesicular steatosis, fatty changes and highly disrupted liver parenchyma. Similarly, CC14 implicated diverse pathology consisting of bridging necrosis and portal tract fibrosis, whereas, Dox, on the other hand, induced hepatotoxicity in the form of prominent sinusoidal dilatation, focal inflammation and apoptosis. Thus, our study made a serious effort in differentiating and evaluating the varied patho-morphological changes induced by diverse hepatotoxins.