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Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice

Cisplatin is the most widely used chemotherapeutic agent. However, it often causes nephrotoxicity, which results in acute kidney injury (AKI). Therefore, we urgently need a drug that can reduce the nephrotoxicity induced by cisplatin. Loganin is a major iridoid glycoside isolated from Corni fructus...

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Autores principales: Kim, Dong-Uk, Kim, Dong-Gu, Choi, Ji-Won, Shin, Joon Yeon, Kweon, Bitna, Zhou, Ziqi, Lee, Ho-Sub, Song, Ho-Joon, Bae, Gi-Sang, Park, Sung-Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866969/
https://www.ncbi.nlm.nih.gov/pubmed/33572597
http://dx.doi.org/10.3390/ijms22031421
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author Kim, Dong-Uk
Kim, Dong-Gu
Choi, Ji-Won
Shin, Joon Yeon
Kweon, Bitna
Zhou, Ziqi
Lee, Ho-Sub
Song, Ho-Joon
Bae, Gi-Sang
Park, Sung-Joo
author_facet Kim, Dong-Uk
Kim, Dong-Gu
Choi, Ji-Won
Shin, Joon Yeon
Kweon, Bitna
Zhou, Ziqi
Lee, Ho-Sub
Song, Ho-Joon
Bae, Gi-Sang
Park, Sung-Joo
author_sort Kim, Dong-Uk
collection PubMed
description Cisplatin is the most widely used chemotherapeutic agent. However, it often causes nephrotoxicity, which results in acute kidney injury (AKI). Therefore, we urgently need a drug that can reduce the nephrotoxicity induced by cisplatin. Loganin is a major iridoid glycoside isolated from Corni fructus that has been used as an anti-inflammatory agent in various pathological models. However, the renal protective activity of loganin remains unclear. In this study, to examine the protective effect of loganin on cisplatin-induced AKI, male C57BL/6 mice were orally administered with loganin (1, 10, and 20 mg/kg) 1 h before intraperitoneal injection of cisplatin (10 mg/kg) and sacrificed at three days after the injection. The administration of loganin inhibited the elevation of blood urea nitrogen (BUN) and creatinine (CREA) in serum, which are used as biomarkers of AKI. Moreover, histological kidney injury, proximal tubule damages, and renal cell death, such as apoptosis and ferroptosis, were reduced by loganin treatment. Also, pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, reduced by loganin treatment. Furthermore, loganin deactivated the extracellular signal-regulated kinases (ERK) 1 and 2 during AKI. Taken together, our results suggest that loganin may attenuate cisplatin-induced AKI through the inhibition of ERK1/2.
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spelling pubmed-78669692021-02-07 Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice Kim, Dong-Uk Kim, Dong-Gu Choi, Ji-Won Shin, Joon Yeon Kweon, Bitna Zhou, Ziqi Lee, Ho-Sub Song, Ho-Joon Bae, Gi-Sang Park, Sung-Joo Int J Mol Sci Article Cisplatin is the most widely used chemotherapeutic agent. However, it often causes nephrotoxicity, which results in acute kidney injury (AKI). Therefore, we urgently need a drug that can reduce the nephrotoxicity induced by cisplatin. Loganin is a major iridoid glycoside isolated from Corni fructus that has been used as an anti-inflammatory agent in various pathological models. However, the renal protective activity of loganin remains unclear. In this study, to examine the protective effect of loganin on cisplatin-induced AKI, male C57BL/6 mice were orally administered with loganin (1, 10, and 20 mg/kg) 1 h before intraperitoneal injection of cisplatin (10 mg/kg) and sacrificed at three days after the injection. The administration of loganin inhibited the elevation of blood urea nitrogen (BUN) and creatinine (CREA) in serum, which are used as biomarkers of AKI. Moreover, histological kidney injury, proximal tubule damages, and renal cell death, such as apoptosis and ferroptosis, were reduced by loganin treatment. Also, pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, reduced by loganin treatment. Furthermore, loganin deactivated the extracellular signal-regulated kinases (ERK) 1 and 2 during AKI. Taken together, our results suggest that loganin may attenuate cisplatin-induced AKI through the inhibition of ERK1/2. MDPI 2021-01-31 /pmc/articles/PMC7866969/ /pubmed/33572597 http://dx.doi.org/10.3390/ijms22031421 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Dong-Uk
Kim, Dong-Gu
Choi, Ji-Won
Shin, Joon Yeon
Kweon, Bitna
Zhou, Ziqi
Lee, Ho-Sub
Song, Ho-Joon
Bae, Gi-Sang
Park, Sung-Joo
Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice
title Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice
title_full Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice
title_fullStr Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice
title_full_unstemmed Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice
title_short Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice
title_sort loganin attenuates the severity of acute kidney injury induced by cisplatin through the inhibition of erk activation in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866969/
https://www.ncbi.nlm.nih.gov/pubmed/33572597
http://dx.doi.org/10.3390/ijms22031421
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