Changes in morphological and biochemical blood parameters following a single administration of cyclophosphamide: dose- and time-dependent effects in an in vivo experimental model

Abstract

Cyclophosphamide (CP) is widely used in clinical practice; however, its administration is associated with pronounced systemic toxicity. Of particular concern is CP-induced hyponatremia, which is accompanied by neurological symptoms. Objective. To describe the dose- and time-dependent changes in plasma sodium concentration as well as a number of associated hematological and biochemical parameters following a single administration of CP to rats.
Materials and methods. In an experiment on outbred male rats (n=30), changes in plasma sodium concentration, hematological and immunological parameters, protein fractions, red blood cell osmotic resistance, and surrogate markers of pro-/antioxidant balance (malondialdehyde and total antioxidant status) were assessed after a single administration of CP at doses of 40 and 140 mg/kg.
Results. On day 5, the high-dose group showed statistically significant decrease in plasma sodium concentration by 17,6 % compared to the control, pronounced leukopenia and thrombocytopenia, as well as an increase in oxidant stress biomarkers. By day 18, some parameters (white blood cells, including relative lymphocyte and neutrophil counts, albumin and α-globulins, malondialdehyde, and total antioxidant status) approached control values, whereas others (absolute lymphocyte count, platelets, leukocyte phagocytic activity, red blood cells resistance) remained altered.
Conclusion. The obtained data characterize the systemic toxicity of CP. This descriptive study documents dose- and time-dependent effects on several morphological and biochemical blood parameters accompanying the cytostatic action of CP. Establishing causal mechanisms underlying electrolyte disturbances requires an extended set of analyzed physiological and renal parameters.