Naringenin ameliorates Cyclophosphamide-induced nephrotoxicity in experimental model

Abstract

Cyclophosphamide (CP) is widely described in the management of several nonneoplastic and neoplastic disorders. Renal damage is the most reported toxic effect of CP in clinical practice. Our study aimed to evaluate the effect of Naringenin (NG) in attenuating renal damage induced by CP in an experimental model. A total of 32 rats were divided into four groups (n = 8): negative control: rats fed on a basal diet, positive control: rats injected intraperitoneally with CP 50 mg/kg of body weight/day, NG 100: rats treated with NG 100 mg/kg/day body orally with concomitant administration of CP as described before, and NG 200: rats treated with NG 200 mg/kg/day body orally daily + CP. At the end of the experimental protocol (21 days), blood creatinine and urea levels were measured. The antioxidant activities and lipid peroxidation products were measured in the renal tissues as indicators of oxidative damage. Histopathological examination and immunohistochemistry staining were also performed on renal tissues. Coadministration of NG along with CP significantly (p < 0.001) improved the renal function and antioxidant capacities compared with positive control animals. Furthermore, histopathological, and immunological examination of renal tissue confirmed the protective effect of NG against CP-induced nephrotoxicity. The current study showed that NG has the potential to protect CP-induced renal damage, which may be beneficial for further studies and the design of NG analogs to be useful in clinical practice against CP-induced nephrotoxicity.

Keywords: Antioxidant; Cyclophosphamide; Inflammation; Naringenin; Renal.

Fig. 1

Rat kidney histopathology (H&E, 200) from the following groups: (A) negative control group demonstrating normal kidney histology; (B) positive control group demonstrating marked distortion of kidney architecture, widespread necrosis of renal tubules, tubular dilatation, epithelial desquamation, vacuolization, and coagulative necrosis; (C) Naringenin 100 mg/kg + cyclophosphamide and (D) Naringenin 200 mg/kg + cyclophosphamide groups, respectively, demonstrating that normal kidney architecture is preserved.

Fig. 2

Immunohistochemistry (200x) of inducible nitric oxide synthase (iNOS) of rat kidneys from (A) negative control group showing no staining (NS); (B) positive control group showing an obviously increased level of iNOS immunostaining in brown color; (C) Naringenin 100 mg /kg + cyclophosphamide group showing a marked decrease in iNOS positivity, and (D) the Naringenin 200 mg /kg + cyclophosphamide group showing no staining (NS).

Fig. 3

Kidney injury molecule-1 (KIM-1) immunohistochemistry of rat kidneys from (A) The negative control group exhibits no staining (NS); (B) the positive control group exhibits a clear rise in KIM-1 immunostaining in a brown hue, (C) the Naringenin 100 mg /kg + cyclophosphamide group exhibits a conspicuous decrease in KIM-1 positivity, and (D) the Naringenin 200 mg /kg + cyclophosphamide group exhibits no staining (NS).