title: Attenuation of renal ischemia/reperfusion injury by oleanolic acid preconditioning via its antioxidant, anti‑inflammatory, and anti‑apoptotic activities.
abstract: Ischemia/reperfusion (I/R)‑associated acute kidney injury is a major clinical problem in both native and transplanted kidneys. Renal I/R, and subsequent renal injury, may be attributed to oxidative stress, inflammation, and apoptosis. Oleanolic acid (OA) is a natural product, which possesses antioxidant, anti‑inflammatory, and anti‑apoptotic activities. The present study aimed to examine the effects of OA preconditioning on renal I/R and the possible underlying mechanisms. In a renal I/R model, rats were administered OA (12.5, 25 and 50 mg/kg) for 15 consecutive days prior to bilateral renal I/R induction. Serum samples and kidneys were then collected and stored for subsequent determination. The results of the present study demonstrated that OA significantly and dose‑dependently attenuated I/R‑induced renal damage. OA prevented renal I/R injury, as evidenced by decreased levels of blood urea nitrogen, creatinine, kidney injury molecule‑1 and lactate dehydrogenase. In addition, OA defended against oxidative stress, as reflected by decreased levels of methane dicarboxylic aldehyde, increased activities of superoxide dismutase, catalase and glutathione peroxidase, and increased glutathione (GSH) levels. Levels of proinflammatory cytokines, interferon‑γ, interleukin (IL)‑6) and myeloperoxidase, were also reduced by OA, whereas the anti‑inflammatory cytokine IL‑10 was increased. Furthermore, OA prevented I/R‑induced apoptotic cell death, and prevented decreases in the mRNA expression levels of nuclear factor erythroid 2‑related factor 2 (Nrf2) and γ‑glutamylcysteine ligase (GCLc). Conversely, buthionine sulphoximine attenuated the protective effects of OA on renal I/R injury. These results indicated that OA preconditioning may prevent I/R‑induced renal damage via antioxidant, anti‑inflammatory, and anti‑apoptotic activities. Stabilization of Nrf2/GCLc signaling and subsequent maintenance of the GSH pool is critical for the protective effects of OA against renal I/R injury. The present study reported a novel therapeutic strategy for the treatment of renal I/R injury.
authors.affiliation: Graduate Faculty, Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Chengmei
authors.initials: C
authors.lastname: Long
authors.affiliation: Department of Organ Transplantation, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jinran
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Organ Transplantation, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Organ Transplantation, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xinchang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Gongxian
authors.initials: G
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000276:immunology; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009828:Oleanolic Acid / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D009828:Oleanolic Acid; D005978:Glutathione