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. 2020 Jun 11;10:9472. doi: 10.1038/s41598-020-66295-0

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Effectiveness of VNS after cisplatin injection. VNS is applied 24 hours after intraperitoneal single injection of cisplatin (25 mg/kg). (a) Plasma creatinine is significantly decreased in the VNS-treated group (plasma creatinine: 0.85 ± 0.09 and 0.53 ± 0.06 mg/dl for Cis-sham and Cis-VNS, 0.25 ± 0.03 and 0.36 ± 0.04 mg/dl for vehicle-sham and vehicle-VNS, respectively; n = 8 or 9; P = 0.0031). (b,c) Representative pictures of PAS staining and tubular injury score. VNS attenuates the degree of tubular injury (tubular injury score: 3.84 ± 0.11 and 2.93 ± 0.25 for Cis-sham and Cis-VNS, 0.0 ± 0.0 and 0.0 ± 0.0 for vehicle-sham and vehicle-VNS, respectively; P = 0.0002). (d–f) The expression of tubular injury marker, Kim-1, is downregulated by VNS. The area fraction of the Kim-1-positive area is analyzed using Image-J software (Kim-1-positive area: 1.35 ± 0.15 and 0.90 ± 0.12% for Cis-sham and Cis-VNS, 0.09 ± 0.02 and 0.07 ± 0.01% for vehicle-sham and vehicle-VNS, respectively; n = 8 or 9; P = 0.0133). Kim-1 expression in the whole kidney is also reduced by VNS (Cis-sham 1154.3 ± 70.0 and Cis-VNS 708.8 ± 119.5-fold change compared with vehicle-sham; P = 0.0005). Data are expressed as mean ± SEM. Scale bar, 100 μm. *P < 0.05, **P < 0.01, ***P < 0.001 (two-way analysis of variance followed by Sidak post-hoc test. VNS, vagus nerve stimulation; Cis, cisplatin; PAS, periodic acid-Schiff; SEM, standard error of the mean.