Amelioration of cisplatin-induced nephrotoxicity in rats by triterpenoid saponin of Terminalia arjuna.
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:


METHODS
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.


CONCLUSIONS
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.
Biochemistry Department, Faculty of Pharmacy, Emergency Hospital, Mansoura University, Mansoura, 35516, Egypt, emyosh@yahoo.com.
Iman O
IO
Sherif
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D029766:Terminalia / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014315:Triterpenes / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D002945:Cisplatin; D016328:NF-kappa B; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D014315:Triterpenes; C110936:Havcr1 protein, rat; C061640:arjunolic acid