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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00119

Magnesium glycyrrhizinate improves methotrexate-induced hepatotoxicity and intestinal damage by reducing COX-2

Yuzhu Cao1, Hang Shi1, Zhiguang Sun1, Jiawei Wu1, Yawen Xia1, Yufei Wang1,  Yuanyuan Wu1, Xiaoman Li1, Wenxing Chen1, Aiyun Wang1 and  Yin Lu1*
  • 1Nanjing University of Chinese Medicine, China

Magnesium isoglycyrrhizinate (MgIG), which has been widely employed to treat chronic hepatitis, is synthesized from 18-β glycyrrhizic acid, a main component of traditional Chinese medicine Glycyrrhiza uralensis Fisch. Although the protective effects of MgIG on methotrexate (MTX)-induced liver toxicity have been well-documented, the underlying mechanism remains elusive. MTX was initially used to treat pediatric acute leukemia, and has been widely applied to psoriasis therapy. However, its clinical applications are limited due to hepatotoxicity and intestinal toxicity. Herein, prophylactic administration of MgIG (9 and 18 mg/kg/day) significantly reduced the levels of aspartate aminotransferase and alanine aminotransferase in the serum of rats receiving intravenous injection of MTX (20 mg/kg body weight). MgIG also attenuated MTX-induced hepatic fibrosis. Moreover, it better protected against MTX-induced hepatocyte apoptosis and decreased the serum level of malondialdehyde than reduced glutathione (80 mg/kg/day) did. Interestingly, MTX-induced COX-2 expression, diarrhea, intestinal permeability and inflammation were attenuated after MgIG administration. In addition, MgIG (9 and 18 mg/kg) reduced MTX-induced colocalization of ZO-1 and connexin 43 in intestinal villi. In conclusion, MgIG exerted beneficial effects on MTX-induced hepatotoxicity and intestinal damage, as a potentially eligible drug for alleviating the hepatic and intestinal side effects of MTX during chemotherapy.

Keywords: Magnesium isoglycyrrhizinate, Methotrexate, Hepatotoxicity, Intestinal damage, Inflammation, COX-2, ZO-1, Cx43

Received: 31 Jul 2018; Accepted: 31 Jan 2019.

Edited by:

Hongjie Zhang, Hong Kong Baptist University, Hong Kong

Reviewed by:

Lei Chen, Fujian Agriculture and Forestry University, China
Mohamed A. Morsy, College of Clinical Pharmacy, King Faisal University, Saudi Arabia  

Copyright: © 2019 Cao, Shi, Sun, Wu, Xia, Wang, Wu, Li, Chen, Wang and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yin Lu, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China, luyingreen@njucm.edu.cn