Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

EASD 2024

Keep up to date with the top stories from the 60th EASD Annual Meeting with our congress hub page.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences
Published in:

16-05-2024 | Acute Pancreatitis | Original Article

Glycyrrhizin Ameliorates Cardiac Injury in Rats with Severe Acute Pancreatitis by Inhibiting Ferroptosis via the Keap1/Nrf2/HO-1 Pathway

Authors: Qingrui Cui, Wei Wang, Jiahui Shi, Fengqing Lai, Shan Luo, Yuhang Du, Xiaofei Wang, Yuke Xiang

Published in: Digestive Diseases and Sciences | Issue 7/2024

Login to get access

Abstract

Background

Severe acute pancreatitis (SAP) is a potential fatal gastrointestinal disease that is usually complicated by myocardial injury and dysfunction. Due to the lack of understanding of the mechanism of SAP-associated cardiac injury (SACI), there is still no complete treatment.

Aims

To explore the alleviative effect and anti-ferroptosis mechanism against SACI of glycyrrhizin (GL), an inhibitor of oxidative stress.

Methods

The SAP model was established by perfusing 5% sodium taurocholate into biliopancreatic duct in rats. H&E staining and serum assays were used to assess the injury changes of pancreas and heart. Echocardiography was used to evaluate the cardiac function. Transmission electron microscopy (TEM) and oxidative stress assays were used to investigate the ferroptosis-related morphological and biochemical changes. Western blot and immunofluorescence were performed to analyzed the expression of ferroptosis-related proteins.

Results

Significant myocardial impairment was found in SAP rats according to increased histopathological scores, serum creatine kinase-MB (CK-MB) and cardiac troponin-I (cTnI) levels, and a decreased fractional shortening and ejection fraction. The decreased mitochondrial cristae and significant expression changes of ferroptosis-related proteins confirmed the presence of ferroptosis in SACI. GL treatment attenuated above-mentioned cardiac tissues damage by inhibiting ferroptosis via restoring the expression of Nrf2 and HO-1 in vivo and in vitro. Treating with ML385 (a Nrf2 inhibitor) or transfecting with siRNA-Nrf2 reversed the protective effect of GL.

Conclusions

Our findings demonstrate the involvement of ferroptosis in SACI and suggest a potential role for GL in the treatment of SACI by supressing ferroptosis via Keap1/Nrf2/HO-1 pathway.
Literature
1.
Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013; 108: 1400–1415, 1416.
2.
Luo Y, Li Z, Ge P, et al. Comprehensive mechanism, novel markers and multidisciplinary treatment of severe acute pancreatitis-associated cardiac injury—a narrative review. J Inflamm Res 2021; 14: 3145–3169.CrossRefPubMedPubMedCentral
3.
4.
5.
Seibt TM, Proneth B, Conrad M. Role of GPX4 in ferroptosis and its pharmacological implication. Free Radic Biol Med 2019; 133: 144–152.CrossRefPubMed
6.
7.
Xie BS, Wang YQ, Lin Y, et al. Inhibition of ferroptosis attenuates tissue damage and improves long-term outcomes after traumatic brain injury in mice. CNS Neurosci Ther 2019; 25: 465–475.CrossRefPubMed
8.
Sheng X, Shan C, Liu J, Yang J, Sun B, Chen D. Theoretical insights into the mechanism of ferroptosis suppression via inactivation of a lipid peroxide radical by liproxstatin-1. Phys Chem Chem Phys 2017; 19: 13153–13159.CrossRefPubMed
9.
Huang Y, Zhang N, Xie C, et al. Lipocalin-2 in neutrophils induces ferroptosis in septic cardiac dysfunction via increasing labile iron pool of cardiomyocytes. Front Cardiovasc Med 2022; 9: 922534.CrossRefPubMedPubMedCentral
10.
Miao W, Chen M, Chen M, et al. Nr2f2 overexpression aggravates ferroptosis and mitochondrial dysfunction by regulating the PGC-1α signaling in diabetes-induced heart failure mice. Mediat Inflamm 2022; 2022: 8373389.CrossRef
11.
Wang Z, Yao M, Jiang L, et al. Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis. Biomed Pharmacother 2022; 154: 113572.CrossRefPubMed
12.
Zhang Y, Ren X, Wang Y, et al. Targeting ferroptosis by polydopamine nanoparticles protects heart against ischemia/reperfusion injury. ACS Appl Mater Interfaces 2021; 13: 53671–53682.CrossRefPubMed
13.
Zhang H, Wang Z, Liu Z, Du K, Lu X. Protective effects of dexazoxane on rat ferroptosis in doxorubicin-induced cardiomyopathy through regulating HMGB1. Front Cardiovasc Med 2021; 8: 685434.CrossRefPubMedPubMedCentral
14.
15.
Wang C, Chen L, Xu C, et al. A comprehensive review for phytochemical, pharmacological, and biosynthesis studies on Glycyrrhiza spp. Am J Chin Med 2020; 48: 17–45.CrossRefPubMed
16.
Upadhyay S, Mantha AK, Dhiman M. Glycyrrhiza glabra (Licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes. J Ethnopharmacol 2020; 258: 112690.CrossRefPubMed
17.
Thakur V, Alcoreza N, Delgado M, Joddar B, Chattopadhyay M. Cardioprotective effect of glycyrrhizin on myocardial remodeling in diabetic rats. Biomolecules 2021; 11: 569.CrossRefPubMedPubMedCentral
18.
Zhao Z, Liu M, Zhang Y, et al. Cardioprotective effect of monoammonium glycyrrhizinate injection against myocardial ischemic injury in vivo and in vitro: involvement of inhibiting oxidative stress and regulating Ca(2+) homeostasis by L-type calcium channels. Drug Des Dev Ther 2020; 14: 331–346.CrossRef
19.
Zhu K, Zhu X, Liu S, Yu J, Wu S, Hei M. Glycyrrhizin attenuates hypoxic–ischemic brain damage by inhibiting ferroptosis and neuroinflammation in neonatal rats via the HMGB1/GPX4 pathway. Oxid Med Cell Longev 2022; 2022: 8438528.CrossRefPubMedPubMedCentral
20.
Jiang T, Cheng H, Su J, et al. Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2/HO-1 signaling pathway. Toxicol In Vitro Int J Publ Assoc BIBRA 2020; 62: 104715.CrossRef
21.
Cai X, Hua S, Deng J, et al. Astaxanthin activated the Nrf2/HO-1 pathway to enhance autophagy and inhibit ferroptosis, ameliorating acetaminophen-induced liver injury. ACS Appl Mater Interfaces 2022; 14: 42887–42903.CrossRefPubMed
22.
Zhou H, Yin C, Zhang Z, et al. Proanthocyanidin promotes functional recovery of spinal cord injury via inhibiting ferroptosis. J Chem Neuroanat 2020; 107: 101807.CrossRefPubMed
23.
Zhu L, Wei M, Yang N, Li X. Glycyrrhizic acid alleviates the meconium-induced acute lung injury in neonatal rats by inhibiting oxidative stress through mediating the Keap1/Nrf2/HO-1 signal pathway. Bioengineered 2021; 12: 2616–2626.CrossRefPubMedPubMedCentral
24.
Aho HJ, Koskensalo SM, Nevalainen TJ. Experimental pancreatitis in the rat. Sodium taurocholate-induced acute haemorrhagic pancreatitis. Scand J Gastroenterol 1980; 15: 411–416.CrossRefPubMed
25.
Wen Y, Sun HY, Tan Z, et al. Abdominal paracentesis drainage ameliorates myocardial injury in severe experimental pancreatitis rats through suppressing oxidative stress. World J Gastroenterol 2020; 26: 35–54.CrossRefPubMedPubMedCentral
26.
Yao J, Miao Y, Zhang Y, et al. Dao-Chi powder ameliorates pancreatitis-induced intestinal and cardiac injuries via regulating the Nrf2-HO-1-HMGB1 signaling pathway in rats. Front Pharmacol 2022; 13: 922130.CrossRefPubMedPubMedCentral
27.
Wen Y, Liu R, Lin N, et al. NADPH oxidase hyperactivity contributes to cardiac dysfunction and apoptosis in rats with severe experimental pancreatitis through ROS-mediated MAPK signaling pathway. Oxid Med Cell Longev 2019; 2019: 4578175.CrossRefPubMedPubMedCentral
28.
Li L, Sun Z, Xu C, et al. Adenovirus-mediated overexpression of sST2 attenuates cardiac injury in the rat with severe acute pancreatitis. Life Sci 2018; 202: 167–174.CrossRefPubMed
29.
30.
Karimani A, Heidarpour M, Moghaddam Jafari A. Protective effects of glycyrrhizin on sub-chronic diazinon-induced biochemical, hematological alterations and oxidative stress indices in male Wistar rats. Drug Chem Toxicol 2019; 42: 300–308.CrossRefPubMed
31.
Cai X, Wang X, Li J, Chen S. Protective effect of glycyrrhizin on myocardial ischemia/reperfusion injury-induced oxidative stress, inducible nitric oxide synthase and inflammatory reactions through high-mobility group box 1 and mitogen-activated protein kinase expression. Exp Ther Med 2017; 14: 1219–1926.CrossRefPubMedPubMedCentral
32.
Cui QR, Ling YH, Wen SH, et al. Gut barrier dysfunction induced by aggressive fluid resuscitation in severe acute pancreatitis is alleviated by necroptosis inhibition in rats. Shock (Augusta Ga) 2019; 52: e107–e116.CrossRefPubMed
33.
Pădureanu V, Florescu DN, Pădureanu R, Ghenea AE, Gheonea DI, Oancea CN. Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review). Exp Ther Med 2022; 23: 197.CrossRefPubMedPubMedCentral
34.
Wang Y, Chen Q, Shi C, Jiao F, Gong Z. Mechanism of glycyrrhizin on ferroptosis during acute liver failure by inhibiting oxidative stress. Mol Med Rep 2019; 20: 4081–4090.PubMedPubMedCentral
35.
Li J, Lu K, Sun F, et al. Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway. J Transl Med 2021; 19: 96.CrossRefPubMedPubMedCentral
Metadata
Title
Glycyrrhizin Ameliorates Cardiac Injury in Rats with Severe Acute Pancreatitis by Inhibiting Ferroptosis via the Keap1/Nrf2/HO-1 Pathway
Authors
Qingrui Cui
Wei Wang
Jiahui Shi
Fengqing Lai
Shan Luo
Yuhang Du
Xiaofei Wang
Yuke Xiang
Publication date
16-05-2024
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2024
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-024-08398-6

Other articles of this Issue 7/2024

Digestive Diseases and Sciences 7/2024 Go to the issue

Original Article

Metabolomic Analysis of Human Cirrhosis and Hepatocellular Carcinoma: A Pilot Study

Image of the Month

Antegrade Electrohydraulic Lithotripsy for Common Bile Duct Stone Using Novel Cholangioscope with Large Working Channel

Invited Commentary

Outpatient Management of Symptomatic Ascites: Bypassing the Path of Least Resistance

Correction

Correction: Single Versus Second Observer vs Artificial Intelligence to Increase the ADENOMA Detection Rate of Colonoscopy—A Network Analysis

Retraction Note

Retraction Note: Insulin-Like Growth Factor Binding Protein-Related Protein 1 Activates Primary Hepatic Stellate Cells via Autophagy Regulated by the PI3K/Akt/mTOR Signaling Pathway

Invited Commentary

Estimating the Penalties of Cytopenias Pre-endoscopy: Is Enough Known?

2024 ESC Congress

Noise pollution dangerous for heart health

Two studies underscore the adverse impact of noise pollution on the risk for and prognosis after myocardial infarction.

Read more

Post-TAVI follow up: deploying virtual assistants

Antihypertensives: more effective at morning or night?

Low Lp(a) levels unlikely to increase the risk of diabetes

» View more highlights on the 2024 ESC Congress hub page

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Read more
Image Credits