Beneficial Effects of Desalinated Magma Seawater in Ameliorating Thioacetamide-induced Chronic Hepatotoxicity

  • Hyunjoo Lee
  • In Soo Suh
  • Minji Woo
  • Mi Jeong Kim
  • Yong-Hwan Jung
  • Yeong Ok SongEmail author
Research Paper


Mineral water is valued for its potent health benefits. In this study, the hepatoprotective effects of desalinated magma seawater (DMS) containing minerals (9,987 mg/L) were investigated in thioacetamide (TAA)-injected rats. Chronic hepatotoxicity was induced via intraperitoneal injections of TAA (200 mg/kg bw), three times a week for 7 weeks. Rats (n = 10 per group) were allocated as TAA-treated groups fed either a normal chow diet (TAA group) or a chow diet containing 0.91% DMS (TAAL group), 2.05% DMS (TAAH group), or 0.05% silymarin (TAAS group). An additional normal group received the chow diet with vehicle (PBS) injections. Compared with the TAA group, the TAAL, TAAH, and TAAS groups had significantly higher body weights and food intake; however, the TAAH group had lower liver weights (P < 0.05). The TAAH and TAAS groups had higher expression levels of Nrf2, HO-1, and NQO1 proteins (P < 0.05) and lower levels of NF-κB, iNOS, and COX-2 than the TAA group (P < 0.05). Additionally, the protein expression levels of detoxification enzymes CYP2E1, MAT, and GST were higher in the TAAL, TAAH, and TAAS groups than in the TAA group (P < 0.05), as confirmed by histological examination. The severe TAA-induced nuclear damage and collagen accumulation in the hepatocytes improved in the DMS-administered groups, indicating that the hepatotoxicity was alleviated. In conclusion, the minerals in DMS likely ameliorate hepatotoxicity by elevating the liver’s antioxidative and anti-inflammatory status. These DMS effects were dose-dependent, with the effects of 2.05% DMS and 0.05% silymarin being comparable.


magma seawater hepatotocixity thioacetamide inflammation antioxidant detoxification 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Azoulay, A., P. Garzon, and M. J. Eisenberg (2001) Comparison of the mineral content of tap water and bottled waters. J. Gen. Intern. Med. 16: 168–175.CrossRefGoogle Scholar
  2. 2.
    Hwang, H. S., H. A. Kim, S. H. Lee, and J. W. Yun (2009) Antiobesity and antidiabetic effects of deep sea water on ob/ob mice. Mar. Biotechnol. 11: 531.CrossRefGoogle Scholar
  3. 3.
    Kim, Y. J., I. S. Jung, H. J. Song, E. Y. Choi, I. S. Choi, and Y. J. Choi (2008) Study of deep ground sea-like water on antioxidant activity and the immune response in RAW264. 7 Macrophages. J. Life Sci. 18: 329–335.CrossRefGoogle Scholar
  4. 4.
    Lee, H. J. and E. K. Sim (2013) A Study on the Industrialization of Deep Seawater in Japan and Korea, and its Implications on the Utilization of Jeju Magma Seawater. Assoc. Japanology East Asia 45: 451–469.Google Scholar
  5. 5.
    Bae, K. H., K. J. Kim, N. Y. Kim, and J. M. Song (2012) In vitro culture of rare plant Bletilla striata using Jeju magma seawater. J. Plant Biotechnol. 39: 281–287.CrossRefGoogle Scholar
  6. 6.
    Kim, B. Y., Y. K. Lee, and D. B. Park (2012) Metabolic activity of desalted ground seawater of Jeju in rat muscle and human liver cells. Fish. Aquat. Sci. 15: 21–27.Google Scholar
  7. 7.
    Messarah, M., F. Klibet, A. Boumendjel, C. Abdennour, N. Bouzerna, M. S. Boulakoud, and A. El Feki (2012) Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats. Exp. Toxicol. Pathol. 64: 167–174.CrossRefGoogle Scholar
  8. 8.
    Trevisan, R., D. F. Mello, A. S. Fisher, P. M. Schuwerack, A. L. Dafre, and A. J. Moody (2011) Selenium in water enhances antioxidant defenses and protects against copper-induced DNA damage in the blue mussel Mytilus edulis. Aquat. Toxicol. 101: 64–71.CrossRefGoogle Scholar
  9. 9.
    Duntas, L. (2009) Selenium and inflammation: underlying antiinflammatory mechanisms. Horm. Metab. Res. 41: 443–447.CrossRefGoogle Scholar
  10. 10.
    Huang, Z., A. H. Rose, and P. R. Hoffmann (2012) The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signaling 16: 705–743.CrossRefGoogle Scholar
  11. 11.
    Yang, M. K. and Y. G. Kim (1999) Protective role of germanium-132 against paraquat-induced oxidative stress in the livers of senescence-accelerated mice. J. Toxicol. Environ. Health, Part A 58: 289–297.CrossRefGoogle Scholar
  12. 12.
    Lee, S. H., S. W. Oh, S. N. Rho, B. H. Lee, H. J. Lee, and D. K. Jin (2006). Effects of germanium-fortified yeast on the serum lipids and immune cell subset. J. Korean Soc. Food Sci. Nutr. 35: 683–689.Google Scholar
  13. 13.
    Lee, Y. J. (2007) Anti-inflammatory effect of germanium in acute lung injury induced by endotoxin. Ph.D. Thesis. University of Youngnam, Gyeongsan, Korea.Google Scholar
  14. 14.
    Baek, D. H., J. W. Jung, T. U. Sohn, and J. K. Kang (2007) Germanium-Fortified Yeast Activates Macrophage, NK Cells and B Cells and Inhibits Tumor Progression in Mice. Microbiol. Biotechnol. Lett. 35: 118–127.Google Scholar
  15. 15.
    Kim, A. D., K. A. Kang, R. Zhang, M. J. Piao, S. Kim, Y. Jee, N. H. Lee, H. J. You, K. S. Ko, and J. W. Hyun (2010) Effects of Jeju water containing vanadium on antioxidant enzymes in vitro. Cancer Prev. Res. 15: 262–267.Google Scholar
  16. 16.
    Kim, A. D., R. Zhang, K. A. Kang, H. J. You, K. G. Kang, and J. W. Hyun (2012) Jeju ground water containing vanadium enhances antioxidant systems in human liver cells. Biol. Trace Elem. Res. 147: 16–24.CrossRefGoogle Scholar
  17. 17.
    Park, S. J., C. K. Youn, J. W. Hyun, and H. J. You (2013) The anti-obesity effect of natural vanadium-containing Jeju ground water. Biol. Trace Elem. Res. 151: 294–300.CrossRefGoogle Scholar
  18. 18.
    Smith, D., R. Pickering, and G. Lewith (2008) A systematic review of vanadium oral supplements for glycaemic control in type 2 diabetes mellitus. QJM 101: 351–358.CrossRefGoogle Scholar
  19. 19.
    Tymchyshin, O. (2013) Hepatoprotective activity of a new germanium-organic biologically active substance (medgerm) in experimental hepatitis. Kazan Med. J. 94: 628–632.Google Scholar
  20. 20.
    Zhou, Z., L. Wang, Z. Song, J. T. Saari, C. J. McClain, and Y. J. Kang (2005) Zinc supplementation prevents alcoholic liver injury in mice through attenuation of oxidative stress. Am. J. Pathol. 166: 1681–1690.CrossRefGoogle Scholar
  21. 21.
    Dabak, J., S. Gazuwa, and G. Ubom (2009) Hepatoprotective potential of calcium and magnesium against cadmium and lead induced hepatotoxicity in wistar rats. Asian J. Biotechnol. 1: 12–19.CrossRefGoogle Scholar
  22. 22.
    Corsini, A. and M. Bortolini (2013) Drug?induced liver injury: the role of drug metabolism and transport. J. Clin. Pharmacol. 53: 463–474.CrossRefGoogle Scholar
  23. 23.
    Khansari, N., Y. Shakiba, and M. Mahmoudi (2009) Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat. Inflammation Allergy Drug Discovery 3: 73–80.CrossRefGoogle Scholar
  24. 24.
    Esmat, A. Y., M. M. Said, A. A. Soliman, K. S. El-Masry, and E. A. Badiea (2013). Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats. Nutrition 29: 258–267.CrossRefGoogle Scholar
  25. 25.
    Salama, S. M., M. A. Abdulla, A. S. AlRashdi, S. Ismail, S. S. Alkiyumi, and S. Golbabapour (2013). Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats. BMC Complementary Altern. Med. 13: 56.CrossRefGoogle Scholar
  26. 26.
    Wong, W. L., M. A. Abdulla, K. H. Chua, U. R. Kuppusamy, Y. S. Tan, and V. Sabaratnam (2012) Hepatoprotective effects of Panus giganteus (Berk.) corner against thioacetamide-(TAA-) induced liver injury in rats. J. Evidence-Based Complementary Altern. Med. 2012. Scholar
  27. 27.
    Kwon, D., J. Kim, K. Cho, and Y. Song (2017) Antioxidative effect of CLA diet and endurance training in liver and skeletal muscles of rat. Biotechnol. Bioprocess Eng. 22: 647–652.CrossRefGoogle Scholar
  28. 28.
    Maxwell, T., K. S. Lee, S. Y. Chun, and K. S. Nam (2017) Mineral-balanced deep sea water enhances the inhibitory effects of chitosan oligosaccharide on atopic dermatitis-like inflammatory response. Biotechnol. Bioprocess Eng. 22: 120–128.CrossRefGoogle Scholar
  29. 29.
    Chen, I. S., Y. Y. Chang, C. L. Hsu, H. W. Lin, M. H. Chang, J. W. Chen, S. S. Chen, and Y. C. Chen (2013) Alleviative effects of deep-seawater drinking water on hepatic lipid accumulation and oxidation induced by a high-fat diet. J. Chin. Med. Assoc. 76: 95–101.CrossRefGoogle Scholar
  30. 30.
    Lee, S. H., D. J. Min, Y. J. Na, J. W. Shim, L. K. Kwon, J. C. Cho, and H. K. Lee (2013) The protective effect of mineral water against UVB irradiation. J. Soc. Cosmet. Scientists Korea 39: 39–46.CrossRefGoogle Scholar
  31. 31.
    Noh, J. R., G. T. Gang, Y. H. Kim, K. J. Yang, C. H. Lee, O. S. Na, G. J. Kim, W. K. Oh, and Y. D. Lee (2010) Desalinated underground seawater of Jeju Island (Korea) improves lipid metabolism in mice fed diets containing high fat and increases antioxidant potential in t-BHP treated HepG2 cells. Nutr. Res. Pract. 4: 3–10.CrossRefGoogle Scholar
  32. 32.
    Chen, I. S., Y. C. Chen, C. H. Chou, R. F. Chuang, L. Y. Sheen, and C. H. Chiu (2012) Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis. J. Sci. Food Agric. 92: 1441–1447.CrossRefGoogle Scholar
  33. 33.
    Xie, Y., G. Wang, H. Wang, X. Yao, S. Jiang, A. Kang, F. Zhou, T. Xie, and H. Hao (2012) Cytochrome P450 dysregulations in thioacetamide induced liver cirrhosis in rats and the counteracting effects of hepatoprotective agents. Drug Metab. Dispos. Scholar
  34. 34.
    Mahidol University National Laboratory Animal Center, Scholar
  35. 35.
    Jung, K., S. H. Hong, M. Kim, J.-S. Han, M.-S. Jang, and Y. O. Song (2015) Antiatherogenic effects of Korean cabbage kimchi with added short arm octopus. Food Sci. Biotech. 24: 249–255.CrossRefGoogle Scholar
  36. 36.
    Das, J. K., M. Severo, C. D. Pereira, E. Patrício, J. Magalhães, R. Monteiro, D. Neves, and M. J. Martins (2017) Natural mineral-rich water ingestion by ovariectomized fructose-fed Sprague-Dawley rats: effects on sirtuin 1 and glucocorticoid signaling pathways. Menopause 24: 563–573.CrossRefGoogle Scholar
  37. 37.
    Pereira, C. D., E. Passos, M. Severo, I. Vitó, X. Wen, F. Carneiro, P. Gomes, R. Monteiro, and M. J. Martins (2016) Ingestion of a natural mineral-rich water in an animal model of metabolic syndrome: effects in insulin signalling and endoplasmic reticulum stress. Horm. Mol. Biol. Clin. Invest. 26: 135–150.Google Scholar
  38. 38.
    Roux, S., C. Baudoin, D. Boute, M. Brazier, V. De La Guéronniere, and M. De Vernejoul (2004) Biological effects of drinking-water mineral composition on calcium balance and bone remodeling markers. J. Nutr., Health Aging 8: 380–385.Google Scholar
  39. 39.
    Fowell, A. J. and J. P. Iredale (2006) Emerging therapies for liver fibrosis. Dig. Dis. 24, 174–183.CrossRefGoogle Scholar
  40. 40.
    Iredale, J. P. (2007) Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J. Clin. Invest. 117: 539–548.CrossRefGoogle Scholar
  41. 41.
    Demirel, U., M. Yalnız, C. Aygün, C. Orhan, M. Tuzcu, K. Sahin, İ. H. Özercan and İ. H. Bahçecioğlu (2012) Allopurinol ameliorates thioacetamide-induced acute liver failure by regulating cellular redox-sensitive transcription factors in rats. Inflammation 35: 1549–1557.CrossRefGoogle Scholar
  42. 42.
    Ruiz, S., P. E. Pergola, R. A. Zager, and N. D. Vaziri (2013) Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease. Kidney Int. 83: 1029–1041.CrossRefGoogle Scholar
  43. 43.
    Mahli, A., A. Koch, B. Czech, P. Peterburs, A. Lechner, J. Haunschild, M. Müller, and C. Hellerbrand (2015) Hepatoprotective effect of oral application of a silymarin extract in carbon tetrachloride-induced hepatotoxicity in rats. Clin. Phytosci. 1: 5.CrossRefGoogle Scholar
  44. 44.
    Fan, S., H. N. Chen, C. J. Wang, W. C. Tseng, H. K. Hsu, and C. F. Weng (2007) Toona sinensis Roem (Meliaceae) leaf extract alleviates liver fibrosis via reducing TGFβ1 and collagen. Food Chem. Toxicol. 45: 2228–2236.CrossRefGoogle Scholar
  45. 45.
    Chou, C. H., Y. C. Chen, M. C. Hsu, W. L. Tsai, C. Y. Chang, and C. H. Chiu (2012) Effect of silymarin on lipid and alcohol metabolism in mice following long?term alcohol consumption. J. Food Biochem. 36: 369–377.CrossRefGoogle Scholar
  46. 46.
    Purohit, V. and D. Russo (2002) Role of S-adenosyl-L-methionine in the treatment of alcoholic liver disease: introduction and summary of the symposium. Alcohol 27: 151–154.CrossRefGoogle Scholar
  47. 47.
    Bishayee, A. and M. Chatterjee (1995) Time course effects of vanadium supplement on cytosolic reduced glutathione level and glutathione S-transferase activity. Biol. Trace Elem. Res. 48: 275–285.CrossRefGoogle Scholar
  48. 48.
    Davis, C. D. and E. O. Uthus (2003) Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats. J. Nutr. 133: 2907–2914.CrossRefGoogle Scholar

Copyright information

© The Korean Society for Biotechnology and Bioengineering and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hyunjoo Lee
    • 1
  • In Soo Suh
    • 2
  • Minji Woo
    • 3
    • 4
  • Mi Jeong Kim
    • 5
  • Yong-Hwan Jung
    • 6
  • Yeong Ok Song
    • 3
    Email author
  1. 1.Wellness Life InstituteJejuKorea
  2. 2.Bio-Convergence Center, Jeju TechnoparkJejuKorea
  3. 3.Department of Food Science and Nutrition and Kimchi Research InstitutePusan National UniversityBusanKorea
  4. 4.Korea Food Research InstituteWanjuKorea
  5. 5.Department of Food and NutritionSilla UniversityBusanKorea
  6. 6.Biodiversity Research InstituteJeju TechnoparkSeogwipoKorea

Personalised recommendations