Impact of single ethanol administration following 12-Hour fasting on hepatic Sulfur-containing amino acid metabolism in mice

Jiwon Hwang; Yubin Song; Doyoung Kwon

doi:10.23264/JJIS.2025.2.1.001

All Issue

2025 Vol.2, Issue 1 Next Page

Research Article

Impact of single ethanol administration following 12-Hour fasting on hepatic Sulfur-containing amino acid metabolism in mice

28 February 2025. pp. 1-6

PDF XML

Abstract

Alcoholic liver disease (ALD) resulting from acute and chronic ethanol intake is a major global cause of liver disorders. ALD is characterized by hepatic injury and steatosis, which are closely associated with the dysregulation of hepatic sulfur-containing amino acid (S-amino acid) metabolism. Among mouse models of binge drinking, a single ethanol administration following 12-hour fasting is frequently employed to evaluate the therapeutic potential of bioactive substances against ALD. However, the effects of ethanol on hepatic S-amino acid metabolism in this model remain unexplored. In this study, male C57BL/6 mice were fasted for 12 hours and then orally administered either saline or ethanol (5 g/kg). Hepatotoxicity, fat accumulation, and changes in hepatic S-amino acid levels and related metabolites were analyzed. Ethanol treatment increased serum alanine aminotransferase activity and hepatic triglyceride levels while decreasing hepatic glutathione levels and the glutathione/oxidized glutathione ratio, indicating hepatocellular damage, steatosis, and oxidative stress. Ethanol also elevated hepatic homocysteine and taurine levels while reducing serine, cystathionine, cysteine, glycine, and glutathione concentrations, suggesting inhibition of transsulfuration and glutathione biosynthesis. These findings suggest that ethanol-induced abnormalities in S-amino acid metabolism may contribute to hepatotoxicity and fat accumulation in this acute ethanol mouse model. Further studies are needed to elucidate the precise molecular mechanisms linking these metabolic alterations to ALD pathogenesis.

Keywords

Alcoholic liver disease

Ethanol

S-amino acid metabolism

Oxidative stress

Steatosis

References

Ahn, C. W., Jun, D. S., Na, J. D., Choi, Y. J. & Kim, Y. C. 2016. Alleviation of hepatic fat accumulation by betaine involves reduction of homocysteine via up-regulation of betaine-homocysteine methyltransferase (BHMT). Biochemical and Biophysical Research Communications 477(3): 440-447. https://doi.org/10.1016/j.bbrc.2016.06.080

10.1016/j.bbrc.2016.06.08027320863

Arumugam, M. K., Chava, S., Perumal, S. K., Paal, M. C., Rasineni, K., Ganesan, M., Donohue, T. M. Jr., Osna, N. A. & Kharbanda, K. K. 2022. Acute ethanol-induced liver injury is prevented by betaine administration. Frontiers in Physiology 13: 940148. https://doi.org/10.3389/fphys.2022.940148

10.3389/fphys.2022.94014836267591PMC9577233

Du, J., He, D., Sun, L. N., Han, T., Zhang, H., Qin, L. P. & Rahman, K. 2010. Semen Hoveniae extract protects against acute alcohol-induced liver injury in mice. Pharmaceutical Biology 48(8): 953-958. https://doi.org/10.3109/13880200903300196

10.3109/1388020090330019620673184

Ji, C. and Kaplowitz, N. 2004. Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury. World Journal of Gastroenterology 10(12): 1699-1708. https://doi.org/10.3748/wjg.v10.i12.1699

10.3748/wjg.v10.i12.169915188490PMC4572253

Jung, Y. S. 2015. Metabolism of sulfur-containing amino acids in the liver: A link between hepatic injury and recovery. Biological & Pharmaceutical Bulletin 38(7): 971-974. https://doi.org/10.1248/bpb.b15-00244

10.1248/bpb.b15-0024426133705

Jung, Y. S., Kim, S. J., Kwon, D. Y., Ahn, C. W., Kim, Y. S., Choi, D. W. & Kim, Y. C. 2013. Alleviation of alcoholic liver injury by betaine involves an enhancement of antioxidant defense via regulation of sulfur amino acid metabolism. Food and Chemical Toxicology 62: 292-298. https://doi.org/10.1016/j.fct.2013.08.049

10.1016/j.fct.2013.08.04923994088

Kharbanda, K. K. 2009. Alcoholic liver disease and methionine metabolism. Seminars in Liver Disease 29(2): 155-165. https://doi.org/10.1055/s-0029-1214371

10.1055/s-0029-121437119387915

Kim, S. J., Jung, Y. S., Kwon, D. Y. & Kim, Y. C. 2008. Alleviation of acute ethanol-induced liver injury and impaired metabolomics of S-containing substances by betaine supplementation. Biochemical and Biophysical Research Communications 368(4): 893-898. https://doi.org/10.1016/j.bbrc.2008.02.003

10.1016/j.bbrc.2008.02.00318267108

Lambert, J. C., Zhou, Z., Wang, L., Song, Z., McClain, C. J. & Kang, Y. J. 2003. Prevention of alterations in intestinal permeability is involved in zinc inhibition of acute ethanol-induced liver damage in mice. Journal of Pharmacology and Experimental Therapeutics 305(3): 880-886.https://doi.org/10.1124/jpet.102.047852

10.1124/jpet.102.04785212626662

Li, Z., Wang, F., Liang, B., Su, Y., Sun, S., Xia, S., Shao, J., Zhang, Z., Hong, M., Zhang, F. & Zheng, S. 2020. Methionine metabolism in chronic liver diseases: An update on molecular mechanism and therapeutic implication. Signal Transduction and Targeted Therapy 5(1): 280. https://doi.org/10.1038/s41392-020-00349-7

10.1038/s41392-020-00349-733273451PMC7714782

Lu, S. C. 1998. Regulation of hepatic glutathione synthesis. Seminars in Liver Disease 18(4): 331-343. https://doi.org/10.1055/s-2007-1007168

10.1055/s-2007-10071689875552

Mato, J. M., Martínez-Chantar, M. L. & Lu, S. C. 2008. Methionine metabolism and liver disease. Annual Review of Nutrition 28: 273-293.https://doi.org/10.1146/annurev.nutr.28.061807.155438

10.1146/annurev.nutr.28.061807.15543818331185

Namachivayam, A. and Valsala Gopalakrishnan, A. 2021. A review on molecular mechanism of alcoholic liver disease. Life Sciences 274: 119328. https://doi.org/10.1016/j.lfs.2021.119328

10.1016/j.lfs.2021.11932833711388

Purohit, V., Abdelmalek, M. F., Barve, S., Benevenga, N. J., Halsted, C. H., Kaplowitz, N., Kharbanda, K. K., Liu, Q. Y., Lu, S. C., McClain, C. J., Swanson, C. & Zakhari, S. 2007. Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: Summary of a symposium. American Journal of Clinical Nutrition 86(1): 14-24. https://doi.org/10.1093/ajcn/86.1.14

10.1093/ajcn/86.1.1417616758

Seo, J., Kwon, D., Kim, S. H., Byun, M. R., Lee, Y. H. & Jung, Y. S. 2023. Role of autophagy in betaine-promoted hepatoprotection against non-alcoholic fatty liver disease in mice. Current Research in Food Science 8: 100663. https://doi.org/10.1016/j.crfs.2023.100663

10.1016/j.crfs.2023.10066338222825PMC10787235

Wu, X., Fan, X., Miyata, T., Kim, A., Cajigas-Du Ross, C. K., Ray, S., Huang, E., Taiwo, M., Arya, R., Wu, J. & Nagy, L. E. 2023. Recent advances in understanding of pathogenesis of alcohol-associated liver disease. Annual Review of Pathology: Mechanisms of Disease 18: 411-438. https://doi.org/10.1146/annurev-pathmechdis-031521-030435

10.1146/annurev-pathmechdis-031521-03043536270295PMC10060166

Xu, L., Guo, W., Dai, J., Cheng, Y., Chen, Y., Liu, W., Xu, J., Su, W., Zhang, X., Wang, C., Yang, H., Xu, J. & Zhang, Y. 2024. Hydrogen gas alleviates acute ethanol-induced hepatotoxicity in mice via modulating TLR4/9 innate immune signaling and pyroptosis. International Immunopharmacology 127: 111399. https://doi.org/10.1016/j.intimp.2023.111399

10.1016/j.intimp.2023.11139938142641

Yu, Y., Tian, Z. Q., Liang, L., Yang, X., Sheng, D. D., Zeng, J. X., Li, X. Y., Shi, R. Y., Han, Z. P. & Wei, L. X. 2019. Babao Dan attenuates acute ethanol-induced liver injury via Nrf2 activation and autophagy. Cell & Bioscience 9: 80. https://doi.org/10.1186/s13578-019-0343-6

10.1186/s13578-019-0343-631583074PMC6771111

Information

Publisher :Jeju Journal of Island Sciences
Publisher(Ko) :제주섬과학회지
Journal Title :Jeju Journal of Island Sciences
Journal Title(Ko) :제주섬과학회지
Volume : 2
No :1
Pages :1-6
Received Date : 2024-12-02
Accepted Date : 2025-02-04
DOI :https://doi.org/10.23264/JJIS.2025.2.1.001

Jeju Journal of Island Sciences ISSN:3022-9456(Online) 제주섬과학회지

All Issue