Attenuation of renal ischemia/reperfusion injury by oleanolic acid preconditioning via its antioxidant, anti‑inflammatory, and anti‑apoptotic activities

Long,Chengmei; Yang,Jinran; Yang,Hua; Li,Xinchang; Wang,Gongxian

doi:10.3892/mmr.2016.5128

Attenuation of renal ischemia/reperfusion injury by oleanolic acid preconditioning via its antioxidant, anti‑inflammatory, and anti‑apoptotic activities

Authors:
- Chengmei Long
- Jinran Yang
- Hua Yang
- Xinchang Li
- Gongxian Wang
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Affiliations: Graduate Faculty, Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Organ Transplantation, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China, Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: April 14, 2016 https://doi.org/10.3892/mmr.2016.5128
Pages: 4697-4704

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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.

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