PMID- 30321543 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 213 DP - 2018 Nov 15 TI - The protective effect of low-energy shock wave on testicular ischemia-reperfusion injury is mediated by the PI3K/AKT/NRF2 pathway. PG - 142-148 LID - S0024-3205(18)30638-6 [pii] LID - 10.1016/j.lfs.2018.10.021 [doi] AB - AIMS: Testicular ischemia-reperfusion (IR) injury is the primary pathophysiological consequence of testicular torsion. Low-energy shock wave (LESW) is an effective treatment for certain diseases. The present study investigated whether LESW could improve on testicular IR injury in rats and examined the involved mechanism. MAIN METHODS: Testicular reperfusion was induced in rats after 1-h ischemia. The first LESW treatment was performed 30 min prior to testicular reperfusion, and then every other day for another 3 applications. LY294002 was applied to investigate the involved mechanism. Testicular morphological changes and malonaldehyde (MDA) level were respectively assessed by hematoxylin-eosin staining. Western blot and thiobarbituric acid method. Western blot, real-time quantitative PCR and immunohistochemistry were performed to assess the apoptosis, the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) pathway the nuclear factor erythroid 2-related factor 2 (NRF2) and vascular endothelial growth factor A (VEGF-A) level in the testis of rats. KEY FINDINGS: LESW improved testicular IR injury in rats. Moreover, LESW upregulated the phosphorylation levels of AKT and glycogen synthase kinase 3beta (GSK-3beta). Also, it upregulated the levels of nuclear NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO-1) in these rats. Nevertheless, LY294002 blocked these protective effects. LESW also upregulated VEGF-A level in rats with testicular IR injury. SIGNIFICANCE: This study demonstrated that LESW could ameliorate testicular IR injury in rats, which might be attributed to the activation of PI3K/AKT/NRF2 pathway. These findings suggested the potential of LESW in the treatment of testicular torsion. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Yu, Gang AU - Yu G AD - Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China; Haikou Center for Medical Synchrotron Radiation Research, Haikou People's Hospital, Haikou 570208, Hainan Province, China. FAU - Guan, Yupeng AU - Guan Y AD - Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China; Haikou Center for Medical Synchrotron Radiation Research, Haikou People's Hospital, Haikou 570208, Hainan Province, China. FAU - Liu, Lin AU - Liu L AD - Emergency and Critical Care Center, Shiyan People's Hospital, Shiyan 442000, Hubei Province, China. FAU - Xing, Jiansheng AU - Xing J AD - Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China. FAU - Li, Jindong AU - Li J AD - Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China. FAU - Cheng, Qing AU - Cheng Q AD - Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China. FAU - Liu, Zhenxiang AU - Liu Z AD - Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China. FAU - Bai, Zhiming AU - Bai Z AD - Department of Urology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University, Haikou 570208, Hainan Province, China; Haikou Center for Medical Synchrotron Radiation Research, Haikou People's Hospital, Haikou 570208, Hainan Province, China. Electronic address: Drzmbai@163.com. LA - eng PT - Journal Article DEP - 20181013 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (NF-E2-Related Factor 2) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, rat) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Extracorporeal Shockwave Therapy/*methods MH - Glycogen Synthase Kinase 3 beta/metabolism MH - Male MH - NF-E2-Related Factor 2/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reperfusion Injury/metabolism/*prevention & control MH - Signal Transduction/drug effects MH - Sound MH - Spermatic Cord Torsion/*therapy MH - Testis/metabolism MH - Vascular Endothelial Growth Factor A/metabolism OTO - NOTNLM OT - Heme oxygenase 1 OT - Low-energy shock wave OT - Nuclear factor erythroid 2-related factor 2 OT - Protein kinase B OT - Testicular ischemia-reperfusion injury OT - Vascular endothelial growth factor A EDAT- 2018/10/16 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/10/16 06:00 PHST- 2018/08/03 00:00 [received] PHST- 2018/10/07 00:00 [revised] PHST- 2018/10/11 00:00 [accepted] PHST- 2018/10/16 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/10/16 06:00 [entrez] AID - S0024-3205(18)30638-6 [pii] AID - 10.1016/j.lfs.2018.10.021 [doi] PST - ppublish SO - Life Sci. 2018 Nov 15;213:142-148. doi: 10.1016/j.lfs.2018.10.021. Epub 2018 Oct 13.