Effect of cyclophosphamide on the microanatomy of liver of albino rats

Javed Ahmad Khan, Shaheen Shahdad, Mohd. Arif Makhdoomi, Sajad Hamid, Gh. Muhammad Bhat, Yasmeen Jan, Sabia Nazir, Zahid Bashir, Shameema Banoo


Background: Cyclophosphamide is widely used in the treatment of various neoplastic diseases and diseases associated with altered immunity. Higher doses used for longer duration effects many organs like urinary bladder, lungs, liver, heart and male reproductive organs.

Methods: To study the effect of cyclophosphamide on the micro anatomy of liver, sixty eight Albino rats were taken and divided into three groups, group A (control group) of 20 animals, were fed with routine diet, group B (low dose group) of 24 animals, were given cyclophosphamide at the dose of 0.5 mg/100 gms in addition to the routine diet and group C (high dose group) of 24 animals, were given high dose of cyclophosphamide at the dose of 0.7 mg/100 gms of weight of animal in addition to the routine diet. The animals were sacrificed at intervals of 3, 6, 9 and 12 weeks, 5 microns sections of the tissue were prepared and stained with Haematoxylin and Eosin stain.

Results: Microscopic changes in liver were apparent in the drug treated animals. In group B the changes appeared after 6 weeks while in group C they started appearing after 3 weeks of drug treatment. The changes were in the form of fatty changes, hemorrhages and central vein congestion.

Conclusion: Cyclophosphamide induces histological changes like fatty infiltration and central vein congestion in the liver. These changes are with low doses given for longer durations and manifest earlier when larger doses
are used. Thus it is advised that patients receiving cyclophosphamide should be periodically evaluated for liver dysfunction.



Cyclophosphamide, Fatty infiltration, Central vein congestion

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OM Colvin. An overview of Cyclophosphamide development and clinical application. Current Pharmaceutical design 1999; 5(8): 555.

Gilman AG, TW Rall. Pharmacokinetics and side effects of Cyclophosphamide. Goodman Gillman Pharmacological basis of therapeutics 1999; 9.

Steinberg SS, Philips FS, Scholle RJ. Pharmacological and pathological effects of alkylating agents; Ann NY Acad. Science 1958; 68: 818.

D. Bissell, K Ataya. Toxic effects of Cyclophosphamide in liver histology. Hepatology (2001).

L.D Deleve. Cellular target of cyclophosphamide toxicity in Murine liver. Hepatology 1996; 24(4): 830-37.

Akay H, Akay T, Secilmis S, Kocak Z, Donalderici O. Hepatotoxicity after low doze Cyclophosphamide therapy. South Med J 2006; 99: 1399-400.

Aubery DA. Massive hepatic necrosis after cyclophosphamide use. Br Med J 1970; 16:58.

George B, Mc Donald, John, T Slattery. Cyclophosphamide induced liver toxicity and mortality. Blood 2003; 101(5): 2043-2048.

McDonald GB, Sharma P, Mathews DS. Venooclusive disease of liver after bone marrow transplantation. Hepatology 1984; 4: 116-22.