Toxicopathological evaluation of sub-therapeutic exposures of cyclophosphamide in Wistar rat

Toxicopathological effects for sub-therapeutic doses of cyclophosphamide (CP) were studied in rats after 28 days repeated dosing.A total of 24 male Wistar rats were procured and randomly allotted to four groups of six rats each.The control group rats received normal saline and treatment group rats received CP orally at 1.5 (low dose), 3.0 (mid dose) and 6.0 (high dose) mg/kg for 28 days.No treatment related clinical signs, mortality, body weight and feed intake were noticed.A significant reduction of TEC, PCV, Hb and monocytes in high dose group, and TLC in mid dose group were noticed.Highly significant reduction of PLT and TLC were noticed in high dose group.Highly significant increase in total cholesterol, ALT and CK in high dose group and significant increase in mid dose group were noticed.A significant increase in BUN, and decrease in total protein and albumin were noticed in high dose group.Highly significant reduction of B-cell and T-cell markers in high dose group and significant reduction in mid dose group were noticed.Bone marrow cytology smear revealed increased myeloid to erythroid ratio and micronucleated polychromatic erythrocytes.At necropsy, sacrificed rats from all dose groups did not reveal any changes except reduced spleen and thymus weights, and increased liver weight in high dose group.Histopathological examination of lymphoid and visceral organs from high dose group revealed architectural alterations, whereas other dose groups did not reveal any alterations.