Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Cyclophosphamide (Cyp) is one of the most commonly used, wide spectrum chemotherapeutic agents. It is mostly used in combinations although it is solitarily efficient, this is because the side effects that follow its administration are dose limiting side effects. On the other hand, although radiation is well known as a hazardous sort of energy, recent studies are interested in studying the beneficial hormetic effect of low doses of gamma radiation. In this study we examined the protective effect of different doses, dose rates, and dose timings of low dose gamma irradiation against Cyp-induced neutropenia. As well as the effect of two different doses/dose rates of gamma irradiation against cyp-induced cardiotoxicity. For neutropenia models, rats were divided into groups for screening of an effective protective dose. For cardiotoxicity tests, rats were divided into seven groups; group 1 served as control group, group 2 served as the model receiving 200 mg/Kg cyp single i.p. dose, group 3 was subjected to low dose rate (LDR) 0.05 gy of irradiation prior to the cyp dose, group 4 was subjected to high dose rate (HDR) 0.25 gy of irradiation prior to the cyp dose, group 5 received total 70 mg/Kg of telmisartan prior to the cyp dose, group 6 received telmisartan dose and 0.05 Gy LDR prior to the cyp, and group 7 received telmisartan dose and 0.25 Gy HDR prior to the cyp dose. Evaluation of this study was based on the effect of cyp on the heart Tn-1 and LDH. As well as examining NF-mB activation pathways; by assaying the content of p65, ImB, IKK-Ü and IKK-ß in the heart muscle using western blot technique

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