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Int J Biol Sci 2009; 5(5):466-473. doi:10.7150/ijbs.5.466 This issue Cite

Research Paper

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

Hassan I El-Sayyad^{1 ✉}, Mohamed F Ismail¹, F M Shalaby¹, RF Abou-El-Magd¹, Rajiv L Gaur², Augusta Fernando², Madhwa HG Raj³, Allal Ouhtit^{1,2 ✉}

2. Department of Pathology and Department of Genetics, Stanley S. Scott Cancer; Louisiana State University Health Science Center, New Orleans, Louisiana, USA;
3. Department of Ob-GYN, Stanley S. Scott Cancer; Louisiana State University Health Science Center, New Orleans, Louisiana, USA;
1. Department of Zoology, Faculty of Science, Mansoura University, Egypt

✉ Correspondence to: Allal Ouhtit, M Ph, Ph D or Hassan I El-Sayyad, PhD, Stanley S. Scott Cancer Center, Louisiana State University Health Science Center, CSRB Building, Room# 748C, 533 Bolivar Street, New Orleans, LA 70112. Ph: 1-504-568-2896 (Office); Fax: 1-504-568-2932; aouhtiedu or elsayyadedu.eg More

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.

Keywords: Cisplatin, doxorubicin, 5-FU, Hepatotoxicity, Rat liver, Chemotherapy.

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