Evaluation of the Effects of Diosmin in Cyclophosphamide-İnduced Nephrotoxicity: An Experimental Animal Study

Abstract

Cyclophosphamide (CYC) is a well-established nephrotoxic agent widely used in the treatment of cancer and various immunosuppressive disorders. Diosmin, a bioactive flavonoid, has been reported to reduce drug-induced adverse effects. This study evaluates the effects of diosmin on CYC-induced nephrotoxicity and explores potential mechanisms involved in CYC-related renal damage. Thirty-two male rats were randomly assigned to four experimental groups: control, diosmin, CYC, and CYC + diosmin. Diosmin (100 mg/kg) was administered once daily for 15 consecutive days, while cyclophosphamide (200 mg/kg) was given as a single dose on the 8th day of the experimental period. Diosmin was associated with attenuation of CYC-induced pathological alterations in renal tissue architecture. It reduced the immunoreactivity of pro-inflammatory mediators (IL-1β, IL-6, TNF-α, and iNOS) and modulated apoptosis by decreasing the pro-apoptotic marker BAX and increasing the anti-apoptotic marker Bcl-2. Although CYC treatment suppressed mTOR and increased SIRT1 immunoreactivity, diosmin co-administration attenuated these alterations. Additionally, markers of renal DNA damage were reduced. Overall, the findings suggest that diosmin may exert favorable effects in CYC-induced nephrotoxicity in this experimental model.