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Abstract
Cyclophosphamide, a cytotoxic alkylating agent, is an extensively used antineoplastic agent. Cardio-toxicity is considered as one of the limiting side effects of its use, which is attributed to oxidative stress. Zingiber officinale is powerful antioxidants against free radicals and oxidative attacks. The aim of this study is to investigate the possible protective effects of Z. officinale against cyclophosphamide induced cardio-toxicity in adult male albino rats. We used 30 adult male albino rats, divided into five groups; Group Ia (-ve control), Group Ib (+ve control), Group II (Z. officinale treated group; 200 mg/kg/day orally), Group III (cyclophosphamide treated group; single dose of 150 mg/kg I.P.), and Group IV (cyclophosphamide and Z. officinale treated group; rats received Z. officinale as before followed by single dose of cyclophosphamide (150 mg/kg)). At the end of experiment, we studied biochemical parameters: oxidative markers (MDA, GSH and Catalase), and Troponin i. The heart tissue was examined by light and electron microscope to evaluate histo-pathological changes and immune-histochemical technique for localization of inducible nitric oxide synthase (iNOS) in the cytoplasm of cardiomyocytes. The result showed increase in troponin I and disturbance of oxidative markers in cyclophosphamide treated group compared to control groups. Whereas these results had significantly improved in cyclophosphamide and Z. officinale treated group. Light and electron microscopic examination revealed disruption in the heart tissue histo-architecture in cyclophosphamide group with strong positive cytoplasmic iNOS immunoreaction in numerous cardiomyocytes by histochemical examination unlike that in cyclophosphamide and Z. officinale treated group which returned near normal. In conclusion, cyclophosphamide has a cardiotoxic effect which can be prevented by Z. officinale supplementation. Further studies about cyclophosphamide toxic effect on the heart and about Z. officinale role in protection are recommended. Key words: Cyclophosphamide, Zingiber officinale, cardiotoxicty.  
Highlights
Cyclophosphamide is an alkylating agent having antineoplastic activity and immunosuppressive properties in many conditions like organ transplantation and systemic lupus erythematosus (Nagler et al, 2013).Cardiotoxicity associated with high-dose cyclophosphamide has been described as a complication of several therapeutic regimens (Kamezaki et al, 2005)and the incidence of fatal cardiomyopathy varies from 2.0 to 17.0%, depending on the different regimens and patient populations (Taniguchi, 2005)
Numerous studies had shown that cyclophosphamide exposure enhances intracellular reactive oxygen species (ROS) production, suggesting that biochemical and physiological side effects may result from its oxidative stress (Manda and Bhatia, 2003)
We aimed to investigate the possible beneficial protective effect of Z. officinale extract on cyclophosphamide induced cardiotoxicity in adult male albino rats
Summary
Cyclophosphamide is an alkylating agent having antineoplastic activity and immunosuppressive properties in many conditions like organ transplantation and systemic lupus erythematosus (Nagler et al, 2013).Cardiotoxicity associated with high-dose cyclophosphamide has been described as a complication of several therapeutic regimens (Kamezaki et al, 2005)and the incidence of fatal cardiomyopathy varies from 2.0 to 17.0%, depending on the different regimens and patient populations (Taniguchi, 2005). The underground stem or rhizome of this plant has been used as a medicine in Asian, Indian and Arabic herbal traditions since ancient times (Altman and Marcussen, 2001) It has been used in herbal medicine practice for the treatment of arthritis, rheumatologic conditions and muscular discomfort. It has been suggested for the treatment of various other conditions, including atherosclerosis, migraine headaches, rheumatoid arthritis, high cholesterol, ulcers, depression, and impotence In addition to these medicinal uses, ginger continues to be valued around the world as an important cooking spice and is believed to help against common cold, flu-like symptoms, and even painful menstrual periods (Grant and Lutz, 2000). We aimed to investigate the possible beneficial protective effect of Z. officinale extract on cyclophosphamide induced cardiotoxicity in adult male albino rats
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