Cyclophosphamide (CP) is a common cytotoxic agent that is employed as a chemotherapeutic and immunosuppressive drug for the management of several neoplastic, hematologic, and autoimmune diseases. Notwithstanding its efficacy in treating diverse tumors, it poses a lot of cytotoxic effects on several human organs. Uterine toxicity is one of the most typical cyclophosphamide adverse effects in female patients.

Natural products have received great interest regarding the protection and regaining of uterine functions and fertility in survivors of cancer. Among these products, the main carotenoid in saffron, crocin (Cr), finds special concern due to its unique properties, which make it act as a strong antioxidant, anti-inflammatory, antidepressant, and even anticancer agent.

The objective of this study was to evaluate the beneficial role of crocin against cyclophosphamide-induced toxic changes in uterine tissue. In this study, 24 Swiss albino mice were divided into 4 groups (6 mice/group); Control: received normal saline (IP); Cr: received crocin (200 mg/kg,IP) daily for 21 consecutive days; CP: received a single dose of cyclophosphamide (75 mg/kg,IP); CP+Cr: received crocin (200 mg/kg,IP) daily for 21 consecutive days.

Results showed that after treatment with crocin, body and uterine weight increased significantly when compared to the CP group. Uterine histopathology, Masson collagen area% fraction, and immunohistochemistry expression of proliferating cell nuclear antigen were also significantly improved by crocin and appeared nearly identical to the control group after being greatly affected and damaged by cyclophosphamide.

In conclusion, crocin administration could reduce the severity of cyclophosphamide-adverse effects on the uterine tissues of mice.