Effect and mechanism of thyroid hormone T3 on the liver oxidative stress in alcoholic liver fibrosis mice

LUO Ren-li LI San-qiang FENG Jia-yang ZHANG Kai-jie LU Shan WU Jun-fei

Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (6) : 753-760.

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Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (6) : 753-760. DOI: 10.16098/j.issn.0529-1356.2024.06.014
Histology,Embryology and Developmental Biology

Effect and mechanism of thyroid hormone T3 on the liver oxidative stress in alcoholic liver fibrosis mice

  • LUO  Ren-li1,2  LI  San-qiang1,2*  FENG  Jia-yang1,2  ZHANG  Kai-jie1,2 LU  Shan1,2  WU  Jun-fei1,2 #br#
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Abstract

Objective To construct a mouse model of alcoholic liver fibrosis and explore the effect of supplementing exogenous thyroid hormone T3 on oxidative stress in liver. Methods  Eighty mice were randomly divided into 6 groups, normal control group, alcoholic liver fibrosis(ALF) model group, and low concentration T3 intervention group (25 μg/kg), medium concentration T3 intervention group (50 μg/kg), high concentration T3 intervention group (100 μg/kg) and T3 control group (the concentration of T3 is 100 μg/kg). A model of mice alcoholic liver fibrosis was established by using alcoholic liquid feed combined with 31.5% ethanol gavage. From the sixth week, mice in the T3 intervention and T3 control group were injected with corresponding concentrations of T3 intraperitoneally for three weeks. Mice in the control and T3 control groups were fed with control liquid feed. The degree of mice liver injury and fibrosis was evaluated through the sirius red staining, Western blotting, and serum biochemical testing. The activity of superoxide dismutase(SOD), the content of glutathione(GSH) and malondialdehyde(MDA) in liver tissue were detected by ELISA, and the protein expressions of microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ) and p62 were detected by immunohistochemistry and Western blotting. Results  The liver structure and function in the ALF group were severely damaged, autophagy was inhibited, and the oxidative stress response was significantly enhanced compared with the control group. Compared with the ALF group, the recovery of liver functional and structure and autophagy were showed in the T3 intervention group, and SOD activity and GSH content in the liver increased in the low and medium concentrations of T3 intervention groups, while MDA content significantly decreased. In the high concentration T3 intervention group, it showed the same increase in SOD activity, a significant decrease in MDA content, while the content of GSH was lower than that in the control group, which was not different with the ALF group. Conclusion  Appropriate supplementation of T3 could affect the occurrence and development of alcoholic liver fibrosis by restoring the liver autophagy to inhibit the oxidative stress response. 

Key words

Thyroid hormone T3 / Alcoholic liver fibrosis / Oxidative stress / Autophagy / Western blotting / Mouse

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LUO Ren-li LI San-qiang FENG Jia-yang ZHANG Kai-jie LU Shan WU Jun-fei. Effect and mechanism of thyroid hormone T3 on the liver oxidative stress in alcoholic liver fibrosis mice[J]. Acta Anatomica Sinica. 2024, 55(6): 753-760 https://doi.org/10.16098/j.issn.0529-1356.2024.06.014

References

 [1] Roehlen  N, Crouchet E, Baumert TF. Liver fibrosis: mechanistic concepts and therapeutic perspectives[J].Cells, 2020, 9(4):875. 
 [2] Zhang  CY, Yuan WG, He P, et al. Liver fibrosis and hepatic stellate cells: etiology, pathological hallmarks and therapeutic targets[J]. World J Gastroenterol, 2016, 22(48): 10512-10522.
 [3] Dhar  D, Baglieri J, Kisseleva T, et al. Mechanisms of liver fibrosis and its role in liver cancer[J]. Exp Biol Med (Maywood), 2020, 245(2): 96-108.
 [4] Min  YQ, Li Sh, Liu XH, et al. Research advances in the cascade interaction between reactive oxygen species/reactive nitrogen species and the NF-κB signaling pathway in liver fibrosis[J]. Journal of Clinical Hepatology, 2023, 39(6): 1454-1460. (in Chinese) 
闵远骞, 李珊,刘湘花,等. 活性氧/活性氮与NF-κB信号通路级联交互在肝纤维化中的作用[J]. 临床肝胆病杂志, 2023. 39(6): 1454-1460.
 [5] Ritter  MJ, Amano I, Hollenberg AN. Thyroid hormone signaling and the liver[J]. Hepatology, 2020, 72(2): 742-752.
 [6] Zheng  MY, He YJ, Liu XY, et al. Research progress on the relationship between liver cirrhosis and thyroid hormones[J]. Zhonghua Gan Zang Bing Za Zhi, 2022, 30(3): 331-334.
 [7] Sinha  RA, Singh BK,  Yen PM. Direct effects of thyroid hormones on hepatic lipid metabolism[J]. Nat Rev Endocrinol, 2018, 14(5): 259-269.
 [8] Hong  XM, Li SQ, Wang ZY,et al. Role of interleukin-6/signal transduction and transcriptional activator 3 signaling pathway in sex difference of alcoholic liver fibrosis[J]. The Chinese Journal of Clinical Pharmacology, 2023, 39(10): 1456-1460. (in Chinese)
洪晓敏, 李三强,王子怡,等. 白细胞介素-6/信号传导与转录激活因子3信号通路在乙醇性肝纤维化性别差异中的作用研究[J]. 中国临床药理学杂志, 2023, 39(10): 1456-1460.
 [9] Kisseleva  T and Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3): 151-166.
 [10] National  Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association, Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for alcoholic liver disease: a 2018 update[J]. Zhonghua Gan Zang Bing Za Zhi, 2018, 26(3): 188-194.
 [11] Tapper  EB, Parikh ND. Mortality due to cirrhosis and liver cancer in the united states, 1999-2016: observational study[J]. BMJ, 2018, 362: k2817.
 [12] Xie  YD, Zhao CQ, Wang JP, et al. Alcohol consumption analysis among patients with liver disease in China[J]. Chin Med J (Engl), 2019, 132(4): 420-430.
 [13] Gines  P, Krag A, Abraldes JG, et al., Liver cirrhosis[J]. Lancet, 2021, 398(10308): 1359-1376.
 [14] Singal  AK, Bataller R, Ahn J, et al., ACG clinical guideline: alcoholic liver disease[J]. Am J Gastroenterol, 2018, 113(2): 175-194.
 [15] Tedeschi  L, Vassalle C, lervasi G, et al. Main factors involved in thyroid hormone action[J]. Molecules, 2021, 26(23): 7337.
 [16] Papineni  JK, Pinnelli VBK, Davanum R. Thyroid hormone levels in chronic alcoholic liver disease patients before and after Treatment[J]. J Clin Diagn Res, 2017, 11(7): BC13-BC16.
 [17] Wang  B, Yang Y, Xu J, et al. Thyroid function and non-alcoholic fatty liver disease in hyperthyroidism patients[J]. BMC Endocr Disord, 2021, 21(1): 27.
 [18] Zhao  M, Xie H, Shan H, et al. Development of thyroid hormones and synthetic thyromimetics in nonalcoholic fatty liver disease[J]. Int J Mol Sci, 2022, 23(3): 1102.
 [19] Zhang  W, Feng C, Jiang H. Novel target for treating Alzheimer’s diseases: crosstalk between the Nrf2 pathway and autophagy[J]. Ageing Res Rev, 2021, 65: 101207.
 [20] Babuta  M, Furi I, Bala S, et al. Dysregulated autophagy and lysosome function are linked to exosome production by micro-RNA 155 in alcoholic liver disease[J]. Hepatology, 2019, 70(6): 2123-2141.
 [21] Deng  Z, Lim J, Wang Q, et al. ALS-FTLD-linked mutations of SQSTM1/p62 disrupt selective autophagy and NFE2L2/NRF2 anti-oxidative stress pathway[J]. Autophagy, 2020, 16(5): 917-931.
 [22] Ping  DB, Cui HY, Sun X, et al. Changes in oxidative stress and ERK signaling pathway during the formation and regression of liver fibrosis[J]. Chinese Hepatology, 2020, 25(11): 1199-1204. (in Chinese) 
平大冰, 崔红艳,孙鑫,等. 肝纤维化形成与消退过程中氧化应激与ERK信号通路变化特点[J]. 肝脏, 2020, 25(11): 1199-1204.
 [23] Fatima  N, Sheikh N, Satoskar AR, et al. Effect of short-term tacrolimus exposure on rat liver: an insight into serum antioxidant status, liver lipid peroxidation, and inflammation[J]. Mediators Inflamm, 2021, 2021: 6613786.
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