Protective Effects of Magnesium Glycyrrhizinate on Methotrexate-Induced Hepatotoxicity and Intestinal Toxicity May Be by Reducing COX-2

Abstract

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 cyclooxygenase-2 (COX-2) expression, intestinal permeability and inflammation were attenuated after MgIG administration. In addition, MgIG (9 and 18 mg/kg) reduced MTX-induced colocalization of zonula occludens-1 (ZO-1) and connexin 43 (Cx43) 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.

Sinapic acid mitigates methotrexate‐induced hepatic injuries in rats through modulation of Nrf‐2/HO‐1 signaling

“…Animals administered MTX experienced significant weight loss and showed an increased liver body weight ratio that was significantly reinstated through pretreatment of SA compared with untreated rats. The present results are in consistent with the previous studies 7,28 . The MTX‐administered model also exhibited a significant rise in liver indices including ALT, AST, and ALP, which is indicative of MTX triggered hepatotoxicity.…”

The protective effects of glycyrrhizic acid on heavy metal ions-induced reproductive toxicity in Chinese hamster ovary cells

“…Supplementation with GA has been proved to be useful in reducing the toxicity of clinical drugs like methotrexate and cocklebur [10,27], but its applicability in the treatment of metal ions-induced toxicity has not been verified. In this respect, this study used CHO cells to investigate the effects of GA on the reproductive toxicity of Cu 2+ and Cd 2+ , with GSH as a positive control.…”

A narrative review of COVID-19: magnesium isoglycyrrhizinate as a potential adjuvant treatment

“…As showed in Figure 2, MgIG improves liver injury induced by various factors, decreases oxidative stress and inflammatory response, normalizes AST, ALT and DBIL levels, and restores liver function (54)(55)(56)(57)(67)(68)(69)(70)(71)163). For kidney injury, MgIG stabilizes the structure of podocytes to reduce proteinuria, pro-inflammatory response and oxidative stress (38,41,75).…”

“…Methotrexate has limited clinical application due to its hepatoenteric toxicity. Prophylactic administration of MgIG (9 or 18 mg/kg ip, qd) can effectively attenuate methotrexate-induced liver fibrosis and hepatotoxicity damage in mice (56). MgIG decreases serum ALT and AST levels, down-regulates liver cyclooxygenase-2 expression, and reduces liver collagen deposition in these animals (56).…”