Monoammonium glycyrrhizinate protects rifampicin- and isoniazid-induced hepatotoxicity via regulating the expression of transporter Mrp2, Ntcp, and Oatp1a4 in liver

Zhou, Liting; Song, Yanqing; Zhao, Jing; Qin, Hong‐Yan; Zhang, Guoqiang; Zhou, Yan; Wu, Xinan

doi:10.3109/13880209.2015.1070878

Cited by 22 publications

(12 citation statements)

References 31 publications

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“…In addition to GSSG reduction by GR, export of GSSG by MRP2 represents another important factor influencing the redox balance of liver cells [11]. Our results show that INH plus RFP treatment resulted in a significant increase in the expression of Mrp2, suggesting that upregulation of Mrp2 during a sustained oxidant insult is expected to shift the transfer of GSSG excreted into bile, and the result was as same as previously reported [12]. Meanwhile, hesperidin could further increase in the expression of Mrp2, suggesting that hesperidin might alleviate oxidative stress by further up regulating the expression of Mrp2.…”

Section: Discussionsupporting

confidence: 90%

Hesperidin Alleviates Oxidative Stress and Upregulates the Multidrug Resistance Protein 2 in Isoniazid and Rifampicin‐Induced Liver Injury in Rats

Zhang

Zhu

Zhou

et al. 2016

J Biochem & Molecular Tox

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Isoniazid (INH) and rifampicin (RFP), two front-line drugs used in tuberculosis therapy, may lead to seriously hepatotoxicity. The current study was carried out to investigate the hepatoprotective effects of hesperidin against INH-and RFP-induced oxidative damage. The liver injury animal model of rats was induced by INH (75 mg/kg) and RFP (150 mg/kg) coadministration for 7 days, and hesperidin, at the dose of 50, 100, and 200 mg/kg, was orally administered to rats 2 h before INH and RFP administration. The biochemical and pathologic examinations were performed after rats were sacrificed. Moreover, the serum and liver glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde (MDA), GSH peroxidase, and GSSG reductase were determined by test kits, and the expression of multidrug resistance proteins 2 (Mrp2) was determined by Western blotting and immunohistochemistry. The results showed that hesperidin significantly alleviated liver injury as indicated by the decreased levels of ALT, AST, bilirubin, total bile acid, and glutathione peroxidase and the increased levels of the GSH/GSSG ratio and the expression of Mrp2. Moreover, hesperidin could effectively reduce the pathological tissue damage. These results indicate that hesperidin can attenuate INH-and RFP-induced oxidative damage, and the underlying mechanism may have correlation with its effect on the upregulation of Mrp2.

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Section: Discussionsupporting

confidence: 90%

Hesperidin Alleviates Oxidative Stress and Upregulates the Multidrug Resistance Protein 2 in Isoniazid and Rifampicin‐Induced Liver Injury in Rats

Zhang

Zhu

Zhou

et al. 2016

J Biochem & Molecular Tox

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“…7,8 MAG has also been used clinically as an injection to treat liver diseases. 9,10 Oxidative stress is a process that causes oxidative damage through imbalance between the production and elimination of oxygen free radicals in the body or cells, which results in the accumulation of reactive oxygen species (ROS). 11 In great quantities, free radicals can cause tissue and cell damage through a series of peroxidation reactions.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, it has been used clinically for immunoregulation, the promotion of bilirubin metabolism, the inhibition of viral hepatitis, the improvement of liver function, and as an adjuvant treatment for radiotherapy and chemotherapy when treating cancer. 10 However, the cardioprotective effects of MAG injection have not been proven. We speculate that MAG exerts a myocardial protective effect by improving oxidative stress and reducing cytoplasmic Ca 2+ concentration by LTCCs.…”

Section: Introductionmentioning

confidence: 99%

<p>Cardioprotective Effect of Monoammonium Glycyrrhizinate Injection Against Myocardial Ischemic Injury in vivo and in vitro: Involvement of Inhibiting Oxidative Stress and Regulating Ca<sup>2+</sup> Homeostasis by L-Type Calcium Channels</p>

Zhao¹,

Liu²,

Zhang³

et al. 2020

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Monoammonium glycyrrhizinate (MAG) is an aglycone of glycyrrhizin that is found in licorice and is often used clinically as an injection to treat liver diseases. However, the effect of MAG injection on cardiac function and its possible cellular mechanisms remain unclear. We explored the protective effects of MAG against myocardial ischemic injury (MII) induced by isoproterenol (ISO), as well as the cellular mechanisms via molecular biology techniques and patch-clamp recording. Methods: A rat model of myocardial ischemia injury was induced by administering ISO (85 mg/kg) subcutaneously for 2 consecutive days. ECG, cardiac functional parameters, CK and LDH levels, SOD and GSH activities, MDA concentration, histological myocardium inspection, mitochondria ultrastructure changes, intracellular calcium concentrations were observed. Influences of MAG on I Ca-L and contraction in isolated rat myocytes were observed by the patch-clamp technique. Results: MAG reduced damage, improved cardiac morphology, inhibited oxidative stress, decreased the generation of reactive oxygen species, and decreased intracellular Ca 2+ concentration. Exposure of the rats' ventricular myocytes to MAG resulted in a concentrationdependent reduction in L-type calcium currents (I Ca-L). MAG reduced I Ca-L in a consistent and time-dependent fashion with a semi-maximal prohibitive concentration of MAG of 14 μM. MAG also shifted the I-V curve of I Ca-L upwards and moved the activation and inactivation curves of I Ca-L to the left. Conclusion: The findings indicate that MAG injection exerts a protective influence on ISOinduced MII by inhibiting oxidative stress and regulating Ca 2+ homeostasis by I Ca-L .

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“…Glycyrrhizin (GL) is a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, as revealed by various animal experimental liver injury models (Li et al, 2014;Yan et al, 2016), and thus is clinically used for treating chronic liver diseases in some Asian countries (Li et al, 2014). Clinical prescription preference for GL is found mainly for treating chronic liver diseases, especially for viral hepatitis in China and Japan (Li et al, 2014), whereas preclinical studies of GL in treating liver diseases have mostly focused on viral hepatitis and drug/toxin-induced hepatotoxicity (Li et al, 2014;Yan et al, 2016;Zhou et al, 2016). However, the effect of GL in preventing NASH is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizin Alleviates Nonalcoholic Steatohepatitis via Modulating Bile Acids and Meta-Inflammation

et al. 2018

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Nonalcoholic steatohepatitis (NASH) is the progressive stage of nonalcoholic fatty liver disease that may ultimately lead to cirrhosis and liver cancer, and there are few therapeutic options for its treatment. Glycyrrhizin (GL), extracted from the traditional Chinese medicine liquorice, has potent hepatoprotective effects in both preclinical animal models and in humans. However, little is currently known about its effects and mechanisms in treating NASH. To explore the effects of GL on NASH, GL or its active metabolite glycyrrhetinic acid (GA) was administered to mice treated with a methionine- and choline-deficient (MCD) diet-induced NASH model, and histologic and biochemical analyses were used to measure the degree of lipid disruption, liver inflammation, and fibrosis. GL significantly improved MCD diet-induced hepatic steatosis, inflammation, and fibrosis and inhibited activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. GL significantly attenuated serum bile acid accumulation in MCD diet-fed mice partially by restoring inflammation-mediated hepatic farnesoid X receptor inhibition. In Raw 264.7 macrophage cells, both GL and GA inhibited deoxycholic acid-induced NLRP3 inflammasome-associated inflammation. Notably, both intraperitoneal injection of GL's active metabolite GA and oral administration of GL prevented NASH in mice, indicating that GL may attenuate NASH via its active metabolite GA. These results reveal that GL, via restoration of bile acid homeostasis and inhibition of inflammatory injury, can be a therapeutic option for treatment of NASH.

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Monoammonium glycyrrhizinate protects rifampicin- and isoniazid-induced hepatotoxicity via regulating the expression of transporter Mrp2, Ntcp, and Oatp1a4 in liver

Abstract: These results indicated that MAG has a protective effects against RIF- and INH-induced hepatotoxicity. The underlying mechanism may have correlation with its effect on regulating the expression of hepatobiliary membrane transporters.

Cited by 22 publications

References 31 publications

Hesperidin Alleviates Oxidative Stress and Upregulates the Multidrug Resistance Protein 2 in Isoniazid and Rifampicin‐Induced Liver Injury in Rats

Hesperidin Alleviates Oxidative Stress and Upregulates the Multidrug Resistance Protein 2 in Isoniazid and Rifampicin‐Induced Liver Injury in Rats

<p>Cardioprotective Effect of Monoammonium Glycyrrhizinate Injection Against Myocardial Ischemic Injury in vivo and in vitro: Involvement of Inhibiting Oxidative Stress and Regulating Ca<sup>2+</sup> Homeostasis by L-Type Calcium Channels</p>

Glycyrrhizin Alleviates Nonalcoholic Steatohepatitis via Modulating Bile Acids and Meta-Inflammation

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