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

Hassan I. El-Sayyad, Mohamed F. Ismail, F. M. Shalaby, R. F. Abou-El-Magd, Rajiv L. Gaur, Augusta Fernando, Madhwa H G Raj, Allal Ouhtit

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investi-gations 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 dissolu-tion 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 col-lagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of di-rect hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron mi-croscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs.

Original languageEnglish
Pages (from-to)466-473
Number of pages8
JournalInternational Journal of Biological Sciences
Volume5
Issue number5
Publication statusPublished - 2009

Fingerprint

cisplatin
doxorubicin
hepatotoxicity
albino
Doxorubicin
Cisplatin
drug
liver
antineoplastic agents
Liver
rats
fibrosis
Light
chemotherapy
Fibrosis
apoptosis
Pharmaceutical Preparations
mitochondrion
ultrastructure
electron microscopy

Keywords

  • 5-Fu
  • Chemotherapy
  • Cisplatin
  • Doxorubicin
  • Hepatotoxicity
  • Rat liver

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology

Cite this

El-Sayyad, H. I., Ismail, M. F., Shalaby, F. M., Abou-El-Magd, R. F., Gaur, R. L., Fernando, A., ... Ouhtit, A. (2009). Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. International Journal of Biological Sciences, 5(5), 466-473.

Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. / El-Sayyad, Hassan I.; Ismail, Mohamed F.; Shalaby, F. M.; Abou-El-Magd, R. F.; Gaur, Rajiv L.; Fernando, Augusta; Raj, Madhwa H G; Ouhtit, Allal.

In: International Journal of Biological Sciences, Vol. 5, No. 5, 2009, p. 466-473.

Research output: Contribution to journalArticle

El-Sayyad, HI, Ismail, MF, Shalaby, FM, Abou-El-Magd, RF, Gaur, RL, Fernando, A, Raj, MHG & Ouhtit, A 2009, 'Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats', International Journal of Biological Sciences, vol. 5, no. 5, pp. 466-473.
El-Sayyad HI, Ismail MF, Shalaby FM, Abou-El-Magd RF, Gaur RL, Fernando A et al. Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. International Journal of Biological Sciences. 2009;5(5):466-473.
El-Sayyad, Hassan I. ; Ismail, Mohamed F. ; Shalaby, F. M. ; Abou-El-Magd, R. F. ; Gaur, Rajiv L. ; Fernando, Augusta ; Raj, Madhwa H G ; Ouhtit, Allal. / Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. In: International Journal of Biological Sciences. 2009 ; Vol. 5, No. 5. pp. 466-473.
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