CYCLOPHOSPHAMIDE-INDUCED GENERATION OF REACTIVE OXYGEN SPECIES - COMPARISON WITH MORPHOLOGICAL-CHANGES IN TYPE-II ALVEOLAR EPITHELIAL-CELLSAND LUNG CAPILLARIES

Cyclophosphamide (CP) causes lung toxicity in animals and humans. The mechanisms of pulmonary damage caused by CP are not fully understood. Possibilities include direct toxicity to pulmonary tissue or indirect toxicity through activation of pulmonary inflammatory cells. The aim o f the present study was the ultrastructural analysis (in transmission electron microscope) of the changes following CP administration within the structures forming the interalveolar septum of the lungs, particu larly type II epithelial cells. An attempt was also made to reveal a c on-elation between the morphological changes, intensity of lipid perox idation in lung tissue homogenates and blood serum collected from the left ventricle of the heart and the alterations in the activities of s uperoxide dismutase (Cu, Zn-SOD) and glutathione reductase (GSSG-R). T he experiment used 40 male Wistar rats of 160-180 g body weight (b.w.) . The animals were divided into two groups. Group I -(20 animals) were given single intraperitoneal (i.p.) dose of 150mg CP/1kg b.w./1ml PBS . Group II -(20 animals) were given single i.p. dose of 1 mi PBS. All experimental animals were sacrificed after 1 (subgroups I, II-1) and 7 (subgroups I, II-7) days of CP (or PBS) treatment. I.p, administratio n of CP caused an increase in lipid peroxidation products (MDA-malondi aldehyde) in lung tissue homogenates especially in subgroup I-1 (p = 0 .00174). No statistical differences, however, were noted in the blood serum MDA levels, although a statistically significant decrease was fo und in GSSG-R (p = 0.00174) and SOD (p = 0.00174) activities in the se rum. The paper dis cusses a potential link between the findings of bio chemical analysis and the morphological changes found within lung tiss ue. Pulmonary trombopoesis was indicated as a possible mechanism preve nting a decrease in blood platelet count following CP administration.