Development of a Model of Immunosuppression in Rabbits Caused by Intravenous Administration of Cyclophosphamide

D. Gajdaj (1), A. Katelnikova(1), K. Kryshen(1), E. Gajdaj(1), Y. Gushin(1), М. Makarova(2)

1 - Institute of pre-clinical studies 188663, Russia, Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, Zavodskaya st., 3-245;
2 - Scientific-Production Organization «Home оf Pharmacy» 188663, Russia, Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, Zavodskaya st., 3-245

Abstract

Today a popular model of secondary immunodeficiency in animals is immunosuppression by administering cyclophosphamide Cyclophosphamide has pronounced immunosuppressive effect with inhibition in small doses of T-lymphocytes subpopulations, in large doses principally B-lymphocytes subpopulations A typical reaction in mammals for the administration of cyclophosphamide is thymus atrophy due to thymocyte apoptosis Most often this model of immunosuppression is used in rodents but sometimes it becomes necessary to administer the drug without demolition of finished dosage form. In this case it is necessary to use larger animals in this model of immunosuppression. An attempt to develop a model of immunosuppression with daily multiple intravenous administration of cyclophosphamide to male rabbits and when administered every other day was made. As criteria for effectiveness of model following parameters were chosen: a decrease in leukocytes level and thymus cellularity by 40–50%, an increase in ratio of cortical substance area to the thymus medulla area by 30–40%, preservation of thymus histoarchitecture. According to results of experiment found: 1. Cyclophosphamide administration by scheme every other day at a dose of 40 mg / kg caused signs of immunosuppression only on the 21st day of the experiment after 10 administrations. Decrease in leukocytes level (≈40%) relative to intact animals was established. Statistically significant decrease in thymus cellularity was also found, which reached ≈60% and statistically significant increase in ratio of cortical substance area to the thymus medulla area by 30% compared with the data of intact group while preserving the histoarchitecture of the organ. 2. Daily intravenous administration of cyclophosphamide caused a decrease in the number of leukocytes in animals treated with cyclophosphamide for 10 days at a dose of 40 mg / kg to 44% compared with the intact group, at a dose of 60 mg / kg - to 66%. Atrophy of thymus with preservation of histoarchitecture was also established, which is showed by a decrease in thymus cellularity by 40% and an increase in the ratio of cortical substance area to the thymus medulla area by 40% in animals treated with cyclophosphamide at a dose of 40 mg / kg relative to intact animals. Thus, to evaluate the efficacy of drugs on the model of secondary immunodeficiency in rabbits two possible shemes can be used: the first is daily intravenous administration of cyclophosphamide at a dose of 40 mg / kg for 20 days with an assessment of indicators at the 10th and 20th days of the experiment, where in period from the 11th to 20th days of the study survival of animals will be evaluated; the second scheme is daily intravenous administration of cyclophosphamide at a dose of 40 mg / kg for 10 days with an assessment of indicators on the 10th and 20th days of the experiment, where in period from the 11th to 20th days of the study, the reversibility of changes caused by cyclophosphamide will be evaluated.

Full text available only in Russian

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