Quercetin and hesperidin attenuate cyclophosphamide-induced renal injury in rats

Abstract

Cyclophosphamide (CP) is an effective chemotherapeutic agent whose clinical use is limited by nephrotoxicity associated with oxidative stress and inflammation. This study investigated the potential nephroprotective effects of quercetin (QUE) and hesperidin (HSP) against CP-induced renal injury in rats. Thirty-six male Wistar albino rats were randomly assigned to six groups (n = 6): Control, QUE, HSP, CP, QUE + CP, and HSP + CP. QUE and HSP were administered orally at a dose of 100 mg/kg/day for 15 days. CP (200 mg/kg) was administered intraperitoneally on the final day to induce nephrotoxicity. Renal function was assessed using serum biochemical parameters (urea, uric acid, creatinine, blood urea nitrogen [BUN], albumin, and total protein), oxidative stress was evaluated by measuring renal antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], and glutathione S-transferase [GST]) together with malondialdehyde (MDA) levels, and histopathological alterations were examined using hematoxylin–eosin staining. CP administration significantly increased serum urea, uric acid, creatinine, blood urea nitrogen, and total protein levels (all p < 0.05). It also increased renal MDA levels (p < 0.001) while reducing SOD (p < 0.05), CAT (p < 0.05), GPx (p < 0.001), and GST (p < 0.001) activities, accompanied by marked histopathological damage characterized by glomerular degeneration, tubular injury, hemorrhage, and inflammatory cell infiltration. Pretreatment with QUE or HSP significantly attenuated these alterations (all p < 0.05). Both flavonoids improved renal biochemical parameters, restored antioxidant defense mechanisms, reduced MDA levels, and ameliorated histopathological alterations compared with the CP group. Although QUE showed numerically greater improvements across several outcomes, direct statistical superiority over HSP was not demonstrated. QUE and HSP exert protective effects against CP-induced nephrotoxicity by reducing oxidative damage and preserving renal tissue integrity. These findings suggest that flavonoid-based adjunctive interventions may represent a promising strategy for reducing chemotherapy-associated renal injury and warrant further mechanistic and translational investigation.