Magnesium isoglycyrrhizinate ameliorates doxorubicin‑induced acute cardiac and hepatic toxicity via anti‑oxidant and anti‑apoptotic mechanisms in mice

Abstract

Abstract. The present study investigated the effects and potential mechanisms of action of magnesium isoglycyrrhizinate (MgIG) in doxorubicin (DOX)-treated mice. Histopathological analysis and western blot analysis were conducted in the liver and heart tissues and biochemical analysis of the serum was performed. The results revealed that MgIG (10, 20 and 40 mg/kg/day) could protect the structure and functions of the liver and heart by inhibiting the activities of the myocardial enzymes creatine kinase (CK), CK-MB and lactate dehydrogenase and the hepatic-specific enzymes aspirate aminotransferase and alanine aminotransferase, increasing the activities of the antioxidants superoxide dismutase and glutathione peroxidase, and inhibiting cellular apoptosis induced by DOX (30 mg/kg). These results demonstrate that inhibiting lipid peroxidation and reducing myocardial and hepatocyte apoptosis may be one of the mechanisms by which MgIG exhibits hepatoprotective and cardioprotective effects in DOX-treated mice.

Magnesium Isoglycyrrhizinate Alleviates Arsenic Trioxide-Induced Cardiotoxicity: Contribution of Nrf2 and TLR4/NF-κB Signaling Pathway

“… 47 , 48 However, MgIG can protect the heart by activating the activity of anti-oxidant enzymes. 49 SOD, CAT, and GSH-Px, as the three main enzymes in the anti-oxidant system, inhibit the further development of oxidative stress in vivo. 49 , 50 The level of MDA could reflect the degree of lipid peroxidation, thereby indirectly reflecting the degree of cell injury.…”

“… 49 SOD, CAT, and GSH-Px, as the three main enzymes in the anti-oxidant system, inhibit the further development of oxidative stress in vivo. 49 , 50 The level of MDA could reflect the degree of lipid peroxidation, thereby indirectly reflecting the degree of cell injury. SOD could convert superoxide anion produced by lipid peroxidation into H 2 O 2 , and CAT and GSH-Px transform H 2 O 2 into oxygen and water, so the activity of these three enzymes are tested at the same time to explore the damage degree of the anti-oxidant system.…”

Magnesium Isoglycyrrhizinate Ameliorates Fibrosis and Disrupts TGF-β-Mediated SMAD Pathway in Activated Hepatic Stellate Cell Line LX2

“…However, we further argued that while these cells seemed to activate the apoptotic machinery, the cells did not exhibit higher cell death compared to activated LX2 cells when subjected to the same concentrations of MgIG. Therefore, this led us to hypothesize that (1) either LO2 cells were indeed more resistant to MgIG-induced cytotoxicity than LX2 cells or (2) that MgIG might indeed have cell specific hepatoprotective effects on LO2 cells, the latter being more plausible due to the number of mechanistic studies supporting its protective effects on hepatocytes ( Zheng et al, 2015 ; Xu et al, 2016 ; Lu et al, 2017 ; Wu et al, 2018 ). In the context of liver fibrosis, as the injury persist, apoptotic hepatocytes may trigger the activation of HSCs and thus deteriorate the fibrotic condition ( Puche et al, 2013 ).…”

“…In addition, studies on either non-alcoholic or alcoholic liver diseases (NALD or ALD) have indicated the potential of MgIG in protecting hepatic cells against fatty acid-induced lipotoxicity ( Cheng et al, 2009 ) and steatosis ( Lu et al, 2017 ). Recently, MgIG has also been shown to exert its hepatoprotective effect against compounds such as cyclophosphamide ( Jiang et al, 2017 ) and doxorubicin ( Wu et al, 2018 ) by increasing the activity of anti-oxidant enzymes and reducing the inflammatory response. Mechanistically, studies have shown that the anti-inflammatory activity of MgIG is attributed to its potential to inhibit inflammatory-associated pathways such as STAT3 ( Tang et al, 2015 ), phospholipase A 2 /arachidonic ( Xie et al, 2015 ) and NF-κB pathways ( Jiang et al, 2017 ; Zhao et al, 2017 ).…”

Magnesium isoglycyrrhizinate positively affects concanavalin A-induced liver damage by regulating macrophage polarization

“…Magnesium isoglycyrrhizinate (MgIG) is a magnesium salt of the 18-alpha-glycyrrhizic acid stereoisomer and is classified as a new molecular compound identified in the roots of the Glycyrrhiza glabra (licorice) tree (Wu et al, 2018). The compound is notable due to its anti-inflammatory and antioxidant effects and has been used to treat liver conditions (Ming & Yin, 2013;van Rossum, Vulto, de Man, Brouwer, & Schalm, 1998).…”