曲美他嗪对急性肝衰竭小鼠肝组织NOX2和NOX4表达的影响

doi:10.3969/j.issn.1672-5069.2021.06.008

Abstract

Abstract: Objective The aim of this experiment was to investigate the effect of trimetazidine on the expression of NOX2 and NOX4 in liver tissues of mice with D-Galn/LPS-induced acute liver failure (ALF). Methods 65 male C57BL/6 mice were randomly divided into control, model, low-, moderate- and high-dose of trimetazidine, as wells as reduced glutathione-intervened group, 10 in each except for those (n=15) in the model. The ALF model was established by D-Galn/LPS intraperitoneal injection. The liver tissue homogenate malondialdehyde (MDA) and peroxidase (CAT) levels were detected, and hepatic NOX2/4 mRNA levels and protein expression were assayed by RT-PCR and Western blot. Results Serum ALT, AST and hepatic MDA levels in model group were (121.4±3.7)U/L,(208.9±27.4)U/L and (51.0±20.5)nmol/mg, all significantly higher than [(35.3±3.2)U/L, (49.9±4.4)U/L and (14.1±5.2) nmol/mg, P＜0.05] in the control, while hepatic CAT level was (51.7±16.8)U/mg, significantly lower than [(110.2±33.7)U/mg, P＜0.05] in the control; the hepatic NOX2/4 mRNA level and their protein expression in the model were (8.2±2.0)/(1.2±0.1) and (2.6±0.1)/(1.3±0.1), significantly higher than [(1.0±0.2)/(0.5±0.1) and (1.0±0.1)/(0.4±0.1), P＜0.05] in the control, serum ALT, AST and hepatic MDA levels in moderate- and high-dose trimetazidine-intervened groups were (86.4±1.00)U/L, (154.0±6.2)U/L and (22.5±1.9)nmol/mg, as well as (81.1±1.5)U/L, (134.7±5.3)U/L and (20.1±3.7)nmol/mg, significantly lower than [(121.4±3.7)U/L, (208.9±27.4)U/L and (51.0±20.5) nmol/mg, P＜0.05] in the model, hepatic CAT level were (99.4±15.5) and (102.3±15.5), significantly higher than [(51.6±16.8), P＜0.05] in the model; hepatic NOX2/4 mRNA levels and their protein expression were (5.6±0.2)/(0.7±0.0) and (5.2±1.4/0.6±0.1) as well as (1.7±0.2)/(0.7±0.2) and (1.5±0.1)/(0.6±0.2), significantly lower than [(8.2±2.0)/(1.2±0.1) and (2.6±0.1)/(1.3±0.1), P＜0.05] in the model. Conclusion Trimetazidine might inhibit the oxidative stress by down-regulation of hepatic NOX2/4 expression and improve the liver functions in D-Galn/LPS-induced mice.

Key words: Acute liver failure, Trimetazidine, Oxidative stress, NOX2, NOX4, Mice

Wang Ya, Luo Tingting, Li Can, et al. Effects of trimetazidine on the expression of NOX2 and NOX4 in liver tissues of mice with acute liver failure[J]. Journal of Practical Hepatology, 2021, 24(6): 799-802.

References

[1] Flamm SL,Yang YX, Singh S, et al. American gastroenterological association institute guidelines for the diagnosis and management of acute liver failure.Gastroenterology,2017,152: 644-647.
[2] Stravitz RT, Lee WM. Acute liver failure. Lancet,2019,394(10201):869-881.
[3] Rifaie N, Saner FH. Critical care management in patients with acute liver failure. Best Pract Res Clin Anaesthesiol,2020,34(1):89-99.
[4] Marzilli M,Vinereanu D,Lopaschuk G,et al. Trimetazidine in cardiovascular medicine.Int J Cardiol, 2019, 293: 39-44.
[5] Ferrari R,Pavasini R,Camici PG,et al. Anti-anginal drugs-beliefs and evidence: systematic review covering 50 years of medical treatment. Eur Heart J, 2019, 40: 190-194.
[6] Amini N,Sarkaki A,Dianat M,et al. Protective effects of naringin and trimetazidine on remote effect of acute renal injury on oxidative stress and myocardial injury through Nrf-2 regulation. Pharmacol Rep, 2019, 71: 1059-1066.
[7] Mahfoudh BA,Selmi R,Bejaoui M,et al. Effectiveness of a single versus repeated administration of trimetazidine in the protection against warm ischemia/reperfusion injury of rat liver.Turk J Med Sci, 2016, 46: 1258-1264.
[8] Shi H,Shi A,Dong L,et al. Chlorogenic acid protects against liver fibrosis in vivo and in vitro through inhibition of oxidative stress.Clin Nutr, 2016, 35: 1366-1373.
[9] Mansouri A, Gattolliat CH, Asselah T. Mitochondrial dysfunction and signaling in chronic liver diseases. Gastroenterology, 2018,155: 629-647.
[10] Reczek CR,Chandel NS. ROS promotes cancer cell survival through calcium signaling.Cancer Cell, 2018, 33: 949-951.
[11] Reichmann D,Voth W,Jakob U. Maintaining a healthy proteome during oxidative stress.Mol Cell, 2018, 69: 203-213.
[12] Parascandolo A,Laukkanen M O. Carcinogenesis and reactive oxygen species signaling: interaction of the NADPH oxidase NOX1-5 and superoxide dismutase 1-3 signal transduction pathways.Antioxid Redox Signal, 2019, 30: 443-486.
[13] Schröder K. NADPH oxidase-derived reactive oxygen species: Dosis facit venenum.Exp Physio, 2019,104: 447-452.
[14] Buvelot H,Jaquet V,Krause KH. Mammalian NADPH oxidases.Methods Mol Biol, 2019, 1982: 17-36.
[15] Janćinová V,Drábiková K,Killinger Z,et al. Novel aspects of the activation of NADPH oxidase in neutrophils of rheumatic patients on biological therapy.Int Immunopharmacol, 2019, 69: 368-372.
[16] Kimura K,Shirabe K,Yoshizumi T,et al. Ischemia-reperfusion injury in fatty liver is mediated by activated NADPH oxidase 2 in rats .Transplantation, 2016, 100: 791-800.
[17] Mochel N, Soledad R,Seronello S,et al. Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection.Hepatology, 2010, 52: 47-59.
[18] Sasaki Yu,Dehnad A,Fish S,et al. NOX4 regulates CCR2 and CCL2 mRNA stability in alcoholic liver disease.Sci Rep, 2017, 7: 46-58.
[19] Luangmonkong T,Suriguga Su,Mutsaers HAM,et al. Targeting oxidative stress for the treatment of liver fibrosis.Rev Physiol Biochem Pharmacol, 2018, 175: 71-102.
[20] Crosas ME,Fabregat I. Role of NADPH oxidases in the redox biology of liver fibrosis.Redox Biol, 2015, 6: 106-111.
[21] Zhang YT,Bi XLJiang F. Cytotoxin-induced NADPH oxides activation: roles in regulation of cell death.Arch Toxicol, 2015, 89: 991-1006.
[22] De MS,Bataller R,Brenner D . NADPH oxidase in the liver: defensive, offensive, or fibrogenic? Gastroenterology, 2006, 131: 272-275.
[23] Tanaka M,Tanaka K,Masaki Y,et al. Intrahepatic microcirculatory disorder, parenchymal hypoxia and NOX4 upregulation result in zonal differences in hepatocyte apoptosis following lipopolysaccharide- and D-galactosamine-induced acute liver failure in rats.Int J Mol Med, 2014, 33: 254-262.
[24] Tang SG,Liu XY,Wang SP,et al. Trimetazidine prevents diabetic cardiomyopathy by inhibiting Nox2/TRPC3-induced oxidative stress.J Pharmacol Sci, 2019, 139: 311-318.

Effects of trimetazidine on the expression of NOX2 and NOX4 in liver tissues of mice with acute liver failure

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Shen Zhenyang, Wang Junjun, Lu Lungen, et al. Impact of YAP signal on proliferation of liver progenitor cells in mice with CDE diet-induced chronic liver injury [J]. Journal of Practical Hepatology, 2021, 24(6): 795-798.
[2]	Wang Zixuan, Wang Mengyu, Li Jingwei, et al. Protective effects of L-ornithine L-aspartate on mice with nonalcoholic steatohepatitis and sarcopenic obesity [J]. Journal of Practical Hepatology, 2021, 24(5): 657-660.
[3]	Shou Diwen, Zhou Yongjian, Xu Haoming, et al. Dynamic changes of blood glucose levels and gut microbiota in mice with high-fat diet-induced metabolic associated fatty liver diseases [J]. Journal of Practical Hepatology, 2021, 24(5): 661-664.
[4]	Li Yan, Lu Lungen, Cai Xiaobo. Effect of HIF-1α on development of nonalcoholic steatohepatitis in mice and in vitro [J]. Journal of Practical Hepatology, 2021, 24(5): 665-668.
[5]	Tang Shuangyi, Wang Xibin, Qiu Yue, et al. Effects of sirolimus on hepatic TLR4 expression and autophagy in mice with partial hepatic warm ischemia-reperfusion injury [J]. Journal of Practical Hepatology, 2021, 24(5): 669-672.
[6]	Yu Lei, Sun Chao, Zhang Manxu. Regulation of intestinal floras and their metabolism functions by ganoderma lucidum plysaceharide in mice with HepG2 cell-induced implanted cancer [J]. Journal of Practical Hepatology, 2021, 24(4): 476-479.
[7]	Peng Jie, Li Bimin, Lei Yupeng. Changes of NOX4 gene and its protein in liver tissues of mice with CCl₄-induced fibrosis and in HSC-T6 cells [J]. Journal of Practical Hepatology, 2021, 24(3): 319-322.
[8]	Wang Lihui, Zhang Jiaxiang , Liu Shuangping, et al. Alleviation of ConA-induced liver injury by protocatechuic acid in mice [J]. Journal of Practical Hepatology, 2021, 24(3): 323-326.
[9]	Lin Liekun, Lu Chunsheng, Zhou Yingsheng, et al. Changes of histone deacetylase mRNA levels after histone acetylation inhibitor management in liver tissue of mice with acute-on-chronic liver failure [J]. Journal of Practical Hepatology, 2021, 24(3): 327-330.
[10]	Dang Ling, Jia Ai, Wang Fang. Prognosis of patients with subacute liver failure by serumlipopolysaccharide binding protein and sCD163 levels [J]. Journal of Practical Hepatology, 2021, 24(3): 447-448.
[11]	Du Qingguo, Lu Jianwen, Wang Jianhua, et al. Somatostatin alleviates liver injury in mice with liver fibrosis by inhibiting endoplasmic reticulum stress [J]. Journal of Practical Hepatology, 2021, 24(2): 172-175.
[12]	Cai Yu, Wang Mengchun, Qiu Xinping, et al. Improvement of liver function and subsiding jaundice by compound glycyrrhizin and adenosylmethionine succinate in the treatment of patients with alcoholic hepatitis [J]. Journal of Practical Hepatology, 2021, 24(1): 71-74.
[13]	Xie huanyu, Gong Jinwei, Zhao MingXing, et al. Inhibitoryeffects of Fe₃O₄ nanometer magnetic carrier-induced hyperthermia under extremely low frequency electromagnetic fields on implanted tumors in nude mice [J]. Journal of Practical Hepatology, 2020, 23(6): 777-780.
[14]	Huang Heming, Liu Yanjun, Fu Rong, et al. Protective effect of bromo- and extra-terminal domain inhibitor (+), JQ1 on LPS / D-Gal-induced acute liver failure in mice [J]. Journal of Practical Hepatology, 2020, 23(6): 781-784.
[15]	Wang Yu, Wang Nan, Liu Yuanyuan, et al.. Effects of herbacetin onhepatic steatosis and intrahepatic oxidative stress in rats with non-alcoholic steatohepatitis [J]. Journal of Practical Hepatology, 2020, 23(5): 626-629.