Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies

Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of <i>Artemisia absinthium</i> extract and its bioactive compound (shikimic acid) against cisplatin-induced rena...

Full description

Bibliographic Details
Main Authors: Jinkyung Lee, Quynh Nhu Nguyen, Jun Yeon Park, Sullim Lee, Gwi Seo Hwang, Noriko Yamabe, Sungyoul Choi, Ki Sung Kang
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Plants
Subjects:
Online Access:https://www.mdpi.com/2223-7747/9/12/1681
_version_ 1797546081908686848
author Jinkyung Lee
Quynh Nhu Nguyen
Jun Yeon Park
Sullim Lee
Gwi Seo Hwang
Noriko Yamabe
Sungyoul Choi
Ki Sung Kang
author_facet Jinkyung Lee
Quynh Nhu Nguyen
Jun Yeon Park
Sullim Lee
Gwi Seo Hwang
Noriko Yamabe
Sungyoul Choi
Ki Sung Kang
author_sort Jinkyung Lee
collection DOAJ
description Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of <i>Artemisia absinthium</i> extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL <i>A. absinthium</i> extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the <i>A. absinthium</i> extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of <i>A. absinthium</i> extract and its mechanism of action against cisplatin-induced renal injury.
first_indexed 2024-03-10T14:25:02Z
format Article
id doaj.art-30a0dd9d285f48afa9b17ac45794b290
institution Directory Open Access Journal
issn 2223-7747
language English
last_indexed 2024-03-10T14:25:02Z
publishDate 2020-12-01
publisher MDPI AG
record_format Article
series Plants
spelling doaj.art-30a0dd9d285f48afa9b17ac45794b2902023-11-20T23:04:16ZengMDPI AGPlants2223-77472020-12-01912168110.3390/plants9121681Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo StudiesJinkyung Lee0Quynh Nhu Nguyen1Jun Yeon Park2Sullim Lee3Gwi Seo Hwang4Noriko Yamabe5Sungyoul Choi6Ki Sung Kang7College of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaDepartment of Food Science and Biotechnology, Kyonggi University, Suwon 16227, KoreaCollege of Bio-Nano Technology, Gachon University, Seongnam-si, Gyeonggi-do 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaNephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of <i>Artemisia absinthium</i> extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL <i>A. absinthium</i> extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the <i>A. absinthium</i> extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of <i>A. absinthium</i> extract and its mechanism of action against cisplatin-induced renal injury.https://www.mdpi.com/2223-7747/9/12/1681<i>Artemisia absinthium</i>shikimic acidcisplatinnephrotoxicityapoptosis
spellingShingle Jinkyung Lee
Quynh Nhu Nguyen
Jun Yeon Park
Sullim Lee
Gwi Seo Hwang
Noriko Yamabe
Sungyoul Choi
Ki Sung Kang
Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies
Plants
<i>Artemisia absinthium</i>
shikimic acid
cisplatin
nephrotoxicity
apoptosis
title Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies
title_full Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies
title_fullStr Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies
title_full_unstemmed Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies
title_short Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies
title_sort protective effect of shikimic acid against cisplatin induced renal injury in vitro and in vivo studies
topic <i>Artemisia absinthium</i>
shikimic acid
cisplatin
nephrotoxicity
apoptosis
url https://www.mdpi.com/2223-7747/9/12/1681
work_keys_str_mv AT jinkyunglee protectiveeffectofshikimicacidagainstcisplatininducedrenalinjuryinvitroandinvivostudies
AT quynhnhunguyen protectiveeffectofshikimicacidagainstcisplatininducedrenalinjuryinvitroandinvivostudies
AT junyeonpark protectiveeffectofshikimicacidagainstcisplatininducedrenalinjuryinvitroandinvivostudies
AT sullimlee protectiveeffectofshikimicacidagainstcisplatininducedrenalinjuryinvitroandinvivostudies
AT gwiseohwang protectiveeffectofshikimicacidagainstcisplatininducedrenalinjuryinvitroandinvivostudies
AT norikoyamabe protectiveeffectofshikimicacidagainstcisplatininducedrenalinjuryinvitroandinvivostudies
AT sungyoulchoi protectiveeffectofshikimicacidagainstcisplatininducedrenalinjuryinvitroandinvivostudies
AT kisungkang protectiveeffectofshikimicacidagainstcisplatininducedrenalinjuryinvitroandinvivostudies