Effects of rosmarinic acid on cyclophosphamide-induced nephrotoxicity in rats

Abstract

Purpose: Cyclophosphamide (CP) is an antineoplastic agent. It is used in the treatment of many types of cancer. Rosmarinic acid (RA) exhibits remarkable biological activities such as anti-inflammatory, antitumor, antibacterial, and antimicrobial effects. This study aimed to evaluate the effect of rosmarinic acid against CP-induced nephrotoxicity. Materials and Methods: Eighteen male Sprague Dawley rats were randomly divided into 3 equal groups; Sham group (n=6): 0.9% saline solution/8 days/oral gavage + 0.9% saline solution/8th day/intraperitoneal, CP group (n=6): 0.9% saline solution/8 days/oral gavage + 200 mg/kg/8th day/intraperitoneal CP, and CP+RA group (n=6): 100 mg/kg/8 days/oral gavage RA + 200 mg/kg/8th day/intraperitoneal CP was applied. Hematoxylin and Eosin, Periodic Acid-Schiff, and Masson’s Trichrome staining were performed on the collected tissues Results: Histopathological evaluation revealed tubular atrophy, glomerular damage, vascular congestion, vacuolization, and interstitial inflammation in the CP group. Histopathological scores were significantly lower in the CP+RA group compared to the CP group. Intertubular fibrosis was observed in the CP group compared to the Sham group. Fibrosis decreased with rosmarinic acid. PAS-stained sections from the CP group showed tubular epithelial vacuolization, brush border, and basal membrane disruption. These findings decreased with rosmarinic acid. The increased blood urea nitrogen level in the CP group was lower in the CP+RA group, while the decreased SOD level in the CP group was higher in the CP+RA group. Conclusion: RA has protective effects against CP causing tubular atrophy, glomerular damage, vascular congestion, vacuolization, and interstitial inflammation in the kidney