title: Renal protective effects of arjunolic acid in a cisplatin-induced nephrotoxicity model.
abstract: Cisplatin is the first platinum-containing anti-cancer drugs. Cisplatin notable side effect of nephrotoxicity limits its use in clinic. Meanwhile, arjunolic acid possesses anti-inflammatory properties and plays protective roles against chemically induced organ pathophysiology. This study was conducted to find out whether arjunolic acid could attenuate kidney damage in rats, and to elucidate its possible mechanism of action. Fifty rats were treated with cisplatin (10mg/kg) in the presence/absence of 100 or 250mg/kg arjunolic acid. Arjunolic acid is given 1h after cisplatin. Morphological changes were assessed in kidney sections stained with Hematoxylin/Eosin and Masson Trichrome. Kidney samples were used for measurements of transforming growth factor (TGF)-β1 and its type 1 receptor (TGF-βR1), tumor necrosis factor (TNF)-α and interleukin (IL)-1β by ELISA. Gene expression NFκB was determined by real time-PCR. Kidney tissue apoptosis was assessed by measuring the activities of caspase-3/8/9. The renal protective effect of arjunolic acid was confirmed by approximately normal appearance of renal tissue and the relatively unaffected serum creatinine and urea levels. Furthermore, arjunolic acid showed dose dependent reduction in cisplatin-induced elevation in renal levels of TGF-βR1, TGF-β1, TNF-α, IL-1β and caspases. These findings demonstrated that arjunolic acid attenuates cisplatin nephrotoxicity either indirectly by enhancing body antioxidant activity or directly through several mechanisms, including inhibition of pro-inflammatory cytokines, blocking activation of TGF-β1, and anti-apoptotic effects.
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, 35516, Egypt.
authors.forename: Nehal M
authors.initials: NM
authors.lastname: Elsherbiny
authors.affiliation: Department of Anatomy & Embryology, Faculty of Medicine, University of Mansoura, 35516, Egypt; Faculty of Medicine, Sharjah University, Sharjah, United Arab Emirates.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Eladl
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, 35516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia. Electronic address: mhgayyar@yahoo.com.
authors.forename: Mohammed M H
authors.initials: MM
authors.lastname: Al-Gayyar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D008517:Phytotherapy / Q000379:methods; D020011:Protective Agents / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029766:Terminalia / Q000737:chemistry; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053583:Interleukin-1beta; D016328:NF-kappa B; D020011:Protective Agents; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C061640:arjunolic acid; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; D020169:Caspases; D002945:Cisplatin
keywords: Caspase-3/8/9; Interleukin (IL)-1β; NADPH oxidase; Transforming growth factor (TGF)-β; Transforming growth factor type 1 receptor (TGF-βR1); Tumor necrosis factor (TNF)-α