Effects of rosmarinic acid against nephrotoxicity induced by cyclophosphamide in rats

In this study, the protective effect of rosmarinic acid (RA) against renal damage caused by cyclophosphamide (CP) was investigated. For this purpose, histopathological and biochemical evaluations were made. 18 Spraque Dawley male rats were randomly divided into three groups: Sham, CP and CP+RA. Sham group was given physiologic serum (PS) by gavage for 8 days from the 1st day of the experiment and PS was administered intraperitoneally on the 8th day of the experiment. CP group was given PS by gavage from the 1st day to the 8th day and a single dose of 200 mg/kg CP was administered on the 8th day of the experiment intraperitoneally. The CP+RA group was given 100 mg/kg RA by gavage for 8 days from first day and 200 mg/kg CP intraperitoneally on the 8th day. On the 9th day of the experiment, the rats were sacrificed and the blood of the rats was taken into the blood tubes. Half of each left kidney removed was taken into a 10% formalin solution for fixation and histological evaluations. Kidney tissue samples were stained using hematoxylin and eosin (H&E), Masson trichrome and periodic acid-Schiff (PAS) staining methods for light microscopic evaluation. Tissue MDA, SOD, CAT assessments were made from the other half of the left kidney. BUN and creatinine in blood serum samples were measured. In histopathological evaluations, tubular atrophy, glomerular damage, vascular congestion, interstitial inflammation, epithelial vacuolization, desquamation in tubular epithelium, leukocyte infiltration and hyaline material accumulation was observed in the kidney sections of the CP group. These disorders were significantly reduced in the CP+RA group compared to the CP group. In the kidney sections with Masson trichrome staining, when compared with the other groups, a slight increase was observed in the intertubular collagen in the CP group. Compared with CP group, there was decrease in the amount of collagen in the area between the tubules in the kidneys in CP+RA group. In PAS stained sections, histopathological findings such as widespread shedding, vacuolization were detected in the tubular epithelium and disruption of brush border and basal membrane were observed in CP group. These disorders decreased in CP+RA group compared to CP group. Increased BUN value in CP group decreased in CP+RA group; whereas decreased SOD value in CP group increased in CP+RA group. Our results show that CP causes histopathological damage in the rat kidney and that RA treatment relatively corrects these disorders caused by CP. Key Words: Rosmarinic acid, Cyclophosphamide, Toxicity, Kidney, Oxidative stress