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Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury.
Transplant Proc. 2015 Jul-Aug; 47(6):1620-6.TP

Abstract

BACKGROUND

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms of renal I/R injury involve inflammation, oxidative stress, and apoptosis. Osthole, a natural coumarin derivative, has potential anti-inflammatory effects. This study investigated the effect of osthole on renal I/R injury and its potential mechanism.

METHODS

We induced renal I/R injury by clamping the left renal artery for 45 min followed by reperfusion, along with a contralateral nephrectomy. We randomly assigned 30 rats to 3 groups (n = 10): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intra-peritoneally with osthole (40 mg/kg) or vehicle (40 mg/kg) 45 min before renal ischemia. We harvested serum and kidneys at 24 h after reperfusion. Renal function and histological changes were assessed. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in renal tissue and serum were examined by means of RT-PCR and ELISA, respectively. The expression of p-p85, p85, p-Akt, Akt, p-p65, and p65 were measured by means of Western blotting.

RESULTS

Osthole pre-treatment significantly attenuated renal dysfunction, renal histological changes, NF-κB activation, and the expression of TNF-α, IL-8, and IL-6 induced by I/R injury, but the activation of PI3K/Akt signaling was further increased.

CONCLUSIONS

Osthole pre-treatment protects rats against renal I/R injury by suppressing NF-κB activation, which is involved in PI3K/Akt signaling activation. Thus, osthole may be a novel practical strategy to prevent renal I/R injury.

Authors+Show Affiliations

Division of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Division of Nephrology, Yibin Second People's Hospital, Yibin, China.Division of Nephrology, Yibin Second People's Hospital, Yibin, China.Division of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.Division of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 18280141016@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26293024

Citation

Xie, D-Q, et al. "Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury." Transplantation Proceedings, vol. 47, no. 6, 2015, pp. 1620-6.
Xie DQ, Sun GY, Zhang XG, et al. Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury. Transplant Proc. 2015;47(6):1620-6.
Xie, D. Q., Sun, G. Y., Zhang, X. G., & Gan, H. (2015). Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury. Transplantation Proceedings, 47(6), 1620-6. https://doi.org/10.1016/j.transproceed.2015.06.011
Xie DQ, et al. Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury. Transplant Proc. 2015 Jul-Aug;47(6):1620-6. PubMed PMID: 26293024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury. AU - Xie,D-Q, AU - Sun,G-Y, AU - Zhang,X-G, AU - Gan,H, PY - 2014/12/07/received PY - 2015/02/20/revised PY - 2015/06/02/accepted PY - 2015/8/22/entrez PY - 2015/8/22/pubmed PY - 2016/4/2/medline SP - 1620 EP - 6 JF - Transplantation proceedings JO - Transplant Proc VL - 47 IS - 6 N2 - BACKGROUND: Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms of renal I/R injury involve inflammation, oxidative stress, and apoptosis. Osthole, a natural coumarin derivative, has potential anti-inflammatory effects. This study investigated the effect of osthole on renal I/R injury and its potential mechanism. METHODS: We induced renal I/R injury by clamping the left renal artery for 45 min followed by reperfusion, along with a contralateral nephrectomy. We randomly assigned 30 rats to 3 groups (n = 10): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intra-peritoneally with osthole (40 mg/kg) or vehicle (40 mg/kg) 45 min before renal ischemia. We harvested serum and kidneys at 24 h after reperfusion. Renal function and histological changes were assessed. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in renal tissue and serum were examined by means of RT-PCR and ELISA, respectively. The expression of p-p85, p85, p-Akt, Akt, p-p65, and p65 were measured by means of Western blotting. RESULTS: Osthole pre-treatment significantly attenuated renal dysfunction, renal histological changes, NF-κB activation, and the expression of TNF-α, IL-8, and IL-6 induced by I/R injury, but the activation of PI3K/Akt signaling was further increased. CONCLUSIONS: Osthole pre-treatment protects rats against renal I/R injury by suppressing NF-κB activation, which is involved in PI3K/Akt signaling activation. Thus, osthole may be a novel practical strategy to prevent renal I/R injury. SN - 1873-2623 UR - https://www.unboundmedicine.com/medline/citation/26293024/Osthole_Preconditioning_Protects_Rats_Against_Renal_Ischemia_Reperfusion_Injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-1345(15)00607-7 DB - PRIME DP - Unbound Medicine ER -