Multiple dose treatment reduces cyclophosphamide-induced ovarian follicular loss in mice

This study compares the effects of single dose and multiple dose treatment of cyclophosphamide (CP) on oxidative stress-mediated follicular damage in mouse ovary. In the first experiment, adult female mice were administered with a single dose of CP (100 mg/kg body weight/mouse) and autopsied 72 hr after treatment. In the second experiment, adult female mice were injected with multiple doses of CP (40 mg/kg body weight/day/mouse for 10 consecutive days) and sacrificed on Day 11. There was a 58, 48, 53, and 51% loss of primordial, primary, preantral, and antral follicles, respectively, following the administration of a single dose of CP, whereas, multiple dose of CP caused only 35% reduction in primordial follicles coupled with 28, 23, and 38%, loss of primary, preantral, and antral follicles, respectively. There was a decrease in activities of the ovarian antioxidant enzymes and increase in reactive oxygen species (ROS) and malondialdehyde (MDA) concentrations following single dose CP, whereas multiple dose treatment caused an increase in activities of these enzymes and decrease in ROS and MDA concentrations. The serum concentration of estradiol was significantly decreased following single or multiple dose treatment. The ovarian damage caused by a single high dose of CP administration is higher than that by multiple doses of smaller amount, though the total amount of CP administered was higher with multiple treatment. The results of the current study reveal the benefit of metronomic chemotherapy in cancer treatment, for its effectiveness in reducing ovarian toxicity, a major side effect in young female patients.