Biomolecules & Therapeutics

  • 제33권1호
  • /
  • Pages.117-128
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  • 2025
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Glutathione's Role in Liver Metabolism and Hangover Symptom Relief: Dysregulation of Protein S-Glutathionylation and Antioxidant Enzymes

  • Hwa-Young Lee (Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital) ;
  • Geum-Hwa Lee (Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital) ;
  • Do-Sung Kim (Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital) ;
  • Young Jae Lim (Non-Clinical Evaluation Center Biomedical Research Institute, Jeonbuk National University Hospital) ;
  • Boram Cho (Food R&D, Samyang Corp.) ;
  • Hojung Jung (Food R&D, Samyang Corp.) ;
  • Hyun-shik Choi (Food R&D, Samyang Corp.) ;
  • Soonok Sa (Food R&D, Samyang Corp.) ;
  • Wookyung Chung (Food R&D, Samyang Corp.) ;
  • Hyewon Lee (School of Pharmacy, Jeonbuk National University) ;
  • Myoung Ja Chung (Department of Pathology, Jeonbuk National University Medical School) ;
  • Junghyun Kim (Department of Oral Pathology, School of Dentistry, Jeonbuk National University) ;
  • Han-Jung Chae (Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital)
  • 투고 : 2024.09.30
  • 심사 : 2024.10.17
  • 발행 : 2025.01.01
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초록

Hangovers from alcohol consumption cause symptoms like headaches, nausea, and fatigue, disrupting daily activities and overall well-being. Over time, they can also lead to inflammation and oxidative stress. Effective hangover relief alleviates symptoms, prevents dehydration, and replenishes energy needed for daily tasks. Natural foods considered high in antioxidants and anti-inflammatory properties may aid in the hepatic breakdown of alcohol. The study aims to investigate the impact of glutathione or its enriched yeast extract, which is recognized for its antioxidant characteristics, on alcohol metabolism and alleviating hangovers in a rat model exposed to binge drinking. In this study, glutathione and its enriched yeast extract controlled hangover behaviour patterns, including locomotor activity. Additionally, it enhanced the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) following ethanol ingestion (3 g/kg). Further, the incorporation of glutathione led to an increase in the expression of antioxidant enzymes, such as SOD and catalase, by activating the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway. This activation reduced the excessive production of reactive oxygen species (ROS) and malondialdehyde. Next, glutathione modulated the activity of cytochrome P450 2E1 (CYP2E1) and the protein expressions of Bax and Bcl2. Besides, in vitro and in vivo investigations with glutathione demonstrated a regulating effect on the pan-s-glutathionylation and its associated protein expression, glutaredoxin 1 (Grx1), glutathione-S-transferase Pi (GST-π), and glutathione reductase (GR). Together, these findings suggest that glutathione or its enriched yeast extract as a beneficial dietary supplement for alleviating hangover symptoms by enhancing alcohol metabolism and its associated Nrf2/Keap1 signalings.

키워드

과제정보

This work was supported by Samyang Corp., Seongnam-si, Republic of Korea.

참고문헌

  1. Bellezza, I., Giambanco, I., Minelli, A. and Donato, R (2018) Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim. Biophys. Acta Mol. Cell. Res. 1865, 721-733.
  2. Castagne, V., Wolinsky, T., Quinn, L. and Virley, D. (2012) Differential behavioral profiling of stimulant substances in the rat using the LABORAS system. Pharmacol. Biochem. Behav. 101, 553-563.
  3. Chen, Y., Han, M., Matsumoto, A., Wang, Y., Thompson, D. C. and Vasiliou, V. (2018) Glutathione and transsulfuration in alcohol-associated tissue injury and carcinogenesis. Adv Exp. Med. Biol. 1032, 37-53.
  4. Choi, E. J., Kim, H., Hong, K. B., Suh, H. J. and Ahn, Y. (2023) Hangover-relieving effect of ginseng berry kombucha fermented by Saccharomyces cerevisiae and Gluconobacteroxydans in ethanol-treated cells and mice model. Antioxidants (Basel) 12, 774.
  5. Contreras-Zentella, M. L., Villalobos-Garcia, D. and Hernandez-Munoz, R. (2022) Ethanol metabolism in the liver, the induction of oxidant stress, and the antioxidant defense system. Antioxidants (Basel) 11, 1258.
  6. Favilli, F., Marraccini, P., Iantomasi, T. and Vincenzini, M. T. (1997) Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters. Br. J. Nutr. 78, 293-300.
  7. Giannini, E. G., Testa, R. and Savarino, V. (2005) Liver enzyme alteration: a guide for clinicians. CMAJ 172, 367-379.
  8. Han, J., Weisbrod, R. M., Shao, D., Watanabe, Y., Yin, X., Bachschmid, M. M., Seta, F., Janssen-Heininger, Y. M. W., Matsui, R., Zang, M., Hamburg, N. M. and Cohen, R. A. (2016) The redox mechanism for vascular barrier dysfunction associated with metabolic disorders: Glutathionylation of Rac1 in endothelial cells. Redox Biol. 9, 306-319.
  9. Haorah, J., Ramirez, S. H., Floreani, N., Gorantla, S., Morsey, B. and Persidsky, Y. (2008) Mechanism of alcohol-induced oxidative stress and neuronal injury. Free Radic. Biol. Med. 45, 1542-1550.
  10. Hyun, J., Han, J., Lee, C., Yoon, M. and Jung, Y. (2021) pathophysiological aspects of alcohol metabolism in the liver. Int. J. Mol. Sci. 22, 5717.
  11. Kim, H., Suh, H. J., Hong, K. B., Jung, E. J. and Ahn, Y. (2023) Combination of cysteine and glutathione prevents ethanol-induced hangover and liver damage by modulation of Nrf2 signaling in HepG2 cells and mice. Antioxidants (Basel) 12, 1885.
  12. Lee, G.-H., Lee, H.-Y., Zhao, L., Rashid, M. M. U., Kim, M. K., Jeong, Y. B., Chae, H.-J. and Shin, Y. S (2024) The role of reactive oxygen species, inflammation, and endoplasmic reticulum stress response in the finasteride protective effect against benign prostate hyperplasia. World J. Mens Health 42, 600-609.
  13. Ma, D., Wang, Z., He, Z., Wang, Z., Chen, Q., Qin, F., Zeng, M. and Chen, J. (2023) Pine pollen extract alleviates ethanol-induced oxidative stress and apoptosis in HepG2 cells via MAPK signaling. Food Chem. Toxicol. 171, 113550.
  14. Mackus, M., Loo, A. J. V., Garssen, J., Kraneveld, A. D., Scholey, A. and Verster, J. C. (2020) The role of alcohol metabolism in the pathology of alcohol hangover. J. Clin. Med. 9, 3421.
  15. McBean, G. J. (2017) Cysteine, glutathione, and thiol redox balance in astrocytes. Antioxidants (Basel) 6, 62.
  16. Park, E. Y., Shimura, N., Konishi, T., Sauchi, Y., Wada, S., Aoi, W., Nakamura, Y. and Sato, K. (2014) Increase in the protein-bound form of glutathione in human blood after the oral administration of glutathione. J. Agric. Food Chem. 62, 6183-6189.
  17. Richie, J. P., Jr., Nichenametla, S., Neidig, W., Calcagnotto, A., Haley, J. S., Schell, T. D. and Muscat, J. E. (2015) Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur. J. Nutr. 54, 251-263.
  18. Seidel, K., Wan, X., Zhang, M., Zhou, Y., Zang, M. and Han, J. (2021) Alcohol binge drinking selectively stimulates protein S-glutathionylation in aorta and liver of ApoE (-/-) mice. Front. Cardiovasc. Med. 8, 649813.
  19. Shiba, S., Nakamoto, N., Chu, P. S., Ojiro, K., Taniki, N., Yamaguchi, A., Morikawa, R., Katayama, T., Yoshida, A., Aoki, R., Teratani, T., Suzuki, T., Miyamoto, T., Hara, S., Yokoyama, A. and Kanai, T. (2021) Acetaldehyde exposure underlies functional defects in monocytes induced by excessive alcohol consumption. Sci. Rep. 11, 13690.
  20. Tan, H. K., Yates, E., Lilly, K. and Dhanda, A. D. (2020) Oxidative stress in alcohol-related liver disease. World J. Hepatol. 12, 332-349.
  21. Wu, D. and Cederbaum, A. I. (2003) Alcohol, oxidative stress, and free radical damage. Alcohol Res. Health 27, 277-284.
  22. Wu, G., Fang, Y. Z., Yang, S., Lupton, J. R. and Turner, N. D. (2004) Glutathione metabolism and its implications for health. J. Nutr. 134, 489-492.
  23. Yamada, H., Ono, S., Wada, S., Aoi, W., Park, E. Y., Nakamura, Y. and Sato, K. (2018) Statuses of food-derived glutathione in intestine, blood, and liver of rat. NPJ Sci. Food 2, 3.
  24. Yang, Y. M., Cho, Y. E. and Hwang, S. (2022) Crosstalk between oxidative stress and inflammatory liver injury in the pathogenesis of alcoholic liver disease. Int. J. Mol. Sci. 23, 774.
  25. Yu, S., Khor, T. O., Cheung, K. L., Li, W., Wu, T. Y., Huang, Y., Foster, B. A., Kan, Y. W. and Kong, A. N. (2010) Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PLoS One 5, e8579.