Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats

Abstract

Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs.

The Possible Protective Role of Melatonin on Doxorubicin Induced Cardiomyopathy of Adult Male Albino Rats

“…These finding were coincided with other investigations [30,31] . Excessive deposition of collagen fibers in DOX treated group was seen.…”

Effects of Grape seed Extract and Origanum Onites Essential Oil on Cisplatin-Induced Hepatotoxicity in Rats

“…These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria. 7 The data in our study also revealed that even a single dose of cisplatin (7 mg kg -1 ) causes considerable damage in the liver, as assessed microscopically. The liver morphology was characterized by severe activation of Kupffer cells, degenerated hepatocytes and moderate enlargement of the sinusoids.…”

“…El-Sayyad et al showed that cisplatin induced drastic abnormalities in liver tissue histology and the ultrastructure with respect to direct toxic effect on hepatocyte organels. 7 Like other chemotherapeutics, cisplatin causes excessive reactive oxygen species (ROS) generation and also induces a decrease in plasma antioxidant levels, which may reflect a failure of the antioxidant defence mechanism against oxidative damage. [8][9][10] Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are endogenous antioxidants and their natural supplements play a role in the prevention of cisplatin-induced oxidative injury in cancer patients.…”

Alantolactone induces apoptosis in glioblastoma cells via GSH depletion, ROS generation, and mitochondrial dysfunction

“…Doxorubicin and Cisplatin are widely used anticancer drugs for various cancers including brain cancer. A large number of reports have documented the hepatotoxicity and nephrotoxicity of these drugs (36)(37)(38)(39). Therefore, alternative therapeutic agents that kill cancer cells without or with low hepatotoxicity and nephrotoxicity are highly desirable.…”