Iman O Sherif1. 1. Biochemistry Department, Faculty of Pharmacy, Emergency Hospital, Mansoura University, Mansoura, 35516, Egypt, emyosh@yahoo.com.
Abstract
BACKGROUND: Cisplatin is a potent anti-tumor compound. Nephrotoxicity-inducing oxidative stress is a common side effect. This study was conducted to find out whether, the triterpenoid saponin of Terminalia arjuna (TA), Arjunolic acid which is a natural antioxidant, could prevent cisplatin-induced renal toxicity and if so, explore its possible renoprotective mechanism. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: CONTROL GROUP: rats received saline injection, cisplatin group: rats injected intraperitoneally with 7 mg/kg cisplatin and Arjunolic acid group: rats received 20 mg/kg Arjunolic acid daily for 10 days with cisplatin injection on day 5. Serum creatinine and blood urea nitrogen (BUN) were determined and kidney sections were obtained for histopathology. Oxidative stress was evaluated in kidney homogenates by measuring malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels. Renal gene expressions of transforming growth factor-beta (TGF-β), nuclear factor-kappa B (NF-κB), kidney injury molecule-1 (Kim-1) and B cell lymphoma-2 (Bcl-2) were estimated. RESULTS: Cisplatin-treated rats showed a significant reduction in renal GSH and a significant elevation of serum creatinine, BUN, MDA and NO renal levels when compared with control. Moreover, upregulation of TGF-β, NF-κB and Kim-1 along with downregulation of Bcl-2 renal expressions were also observed in cisplatin-treated rats in comparison to control. All these markers were significantly reversed by TA triterpenoid saponin administration. CONCLUSION: Arjunolic acid ameliorated the nephrotoxic biochemical changes induced by cisplatin supporting its renoprotective effects which may be mediated by attenuation of oxidative stress markers, downregulation of renal expressions of fibrotic (TGF-β), inflammatory (NF-κB) and kidney injury (Kim-1) markers along with upregulation of renal antiapoptotic marker (Bcl-2) gene expressions.
BACKGROUND:Cisplatin is a potent anti-tumor compound. Nephrotoxicity-inducing oxidative stress is a common side effect. This study was conducted to find out whether, the triterpenoidsaponin of Terminalia arjuna (TA), Arjunolic acid which is a natural antioxidant, could prevent cisplatin-induced renal toxicity and if so, explore its possible renoprotective mechanism. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: CONTROL GROUP: rats received saline injection, cisplatin group: rats injected intraperitoneally with 7 mg/kg cisplatin and Arjunolic acid group: rats received 20 mg/kg Arjunolic acid daily for 10 days with cisplatin injection on day 5. Serum creatinine and blood ureanitrogen (BUN) were determined and kidney sections were obtained for histopathology. Oxidative stress was evaluated in kidney homogenates by measuring malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels. Renal gene expressions of transforming growth factor-beta (TGF-β), nuclear factor-kappa B (NF-κB), kidney injury molecule-1 (Kim-1) and B cell lymphoma-2 (Bcl-2) were estimated. RESULTS:Cisplatin-treated rats showed a significant reduction in renal GSH and a significant elevation of serum creatinine, BUN, MDA and NO renal levels when compared with control. Moreover, upregulation of TGF-β, NF-κB and Kim-1 along with downregulation of Bcl-2 renal expressions were also observed in cisplatin-treated rats in comparison to control. All these markers were significantly reversed by TAtriterpenoidsaponin administration. CONCLUSION:Arjunolic acid ameliorated the nephrotoxic biochemical changes induced by cisplatin supporting its renoprotective effects which may be mediated by attenuation of oxidative stress markers, downregulation of renal expressions of fibrotic (TGF-β), inflammatory (NF-κB) and kidney injury (Kim-1) markers along with upregulation of renal antiapoptotic marker (Bcl-2) gene expressions.
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