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Original Communication

Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis

Published Online:https://doi.org/10.1024/0300-9831/a000515

Abstract.Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.

Literature

  • Bellentani, S., Scaglioni, F., Marino, M. and Bedogni, G. (2010) Epidemiology of non-alcoholic fatty liver disease. Dig. Dis. 28, 155–61. First citation in articleCrossrefGoogle Scholar

  • Ludwig, J., Viggiano, T.R., McGill, D.B. and Oh, B.J. (1980) Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo. Clin. Proc. 55, 434–8. First citation in articleGoogle Scholar

  • Brunt, E.M. (2001) Nonalcoholic steatohepatitis: definition and pathology. Semin. Liver. Dis. 21, 3–16. First citation in articleCrossrefGoogle Scholar

  • Matteoni, C.A., Younossi, Z.M., Gramlich, T., Boparai, N., Liu, Y.C. and McCullough, A.J. (1999) Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116, 1413–9. First citation in articleCrossrefGoogle Scholar

  • Powell, E.E., Cooksley, W.G., Hanson, R., Searle, J., Halliday, J.W. and Powell, L.W. (1990) The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 11, 74–80. First citation in articleCrossrefGoogle Scholar

  • Adams, L.A., Lymp, J.F., St.Sauver, J., Sanderson, S.O., Lindor, K.D., Feldstein, A. and Anqulo P. (2005) The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113–21. First citation in articleCrossrefGoogle Scholar

  • Samuel, V.T. and Shulman, G.I. (2012) Mechanisms for insulin resistance: common threads and missing links. Cell 148, 852–71. First citation in articleCrossrefGoogle Scholar

  • Cusi, K. (2012) Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology 142, 711–25. First citation in articleCrossrefGoogle Scholar

  • Dowman, J.K., Armstrong, M.J., Tomlinson, J.W. and Newsome, P.N. (2011) Current therapeutic strategies in non-alcoholic fatty liver disease. Diabetes. Obes. Metab. 13, 692–702. First citation in articleCrossrefGoogle Scholar

  • Harrison, S.A., Torgerson, S., Hayashi, P., Ward, J. and Schenker, S. (2003) Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am. J. Gastroenterol. 98, 2485–90. First citation in articleCrossrefGoogle Scholar

  • Li, Y. and Schellhorn, H.E. (2007) New developments and novel therapeutic perspectives for vitamin C. J. Nutr. 137, 2171–84. First citation in articleCrossrefGoogle Scholar

  • Sweetman, S.F., Strain, J.J. and McKelvey-Martin, V.J. (1997) Effect of antioxidant vitamin supplementation on DNA damage and repair in human lymphoblastoid cells. Nutr. Cancer 27, 122–30. First citation in articleCrossrefGoogle Scholar

  • Barja, G., Lopez-Torres, M., Pérez-Campo, R., Rojas, C., Cadenas, S., Prat, J. and Pamplona, R. (1994) Dietary vitamin C decreases endogenous protein oxidative damage, malondialdehyde, and lipid peroxidation and maintains fatty acid unsaturation in the guinea pig liver. Free. Radic. Biol. Med. 17, 105–15. First citation in articleCrossrefGoogle Scholar

  • Nishikimi, M., Koshizaka, T., Ozawa, T. and Yagi, K. (1988) Occurrence in humans and guinea pigs of the gene related to their missing enzyme L-gulonogamma-lactone oxidase. Arch. Biochem. Biophys.267, 842–6. First citation in articleCrossrefGoogle Scholar

  • MacDonald, L., Thumser, A.E. and Sharp, P. (2002) Decreased expression of the vitamin C transporter SVCT1 by ascorbic acid in a human intestinal epithelial cell line. Br. J.Nutr. 87, 97–100. First citation in articleCrossrefGoogle Scholar

  • Padayatty, S.J., Sun, H., Wang, Y.H., Riordan, H.D., Hewitt, S.M. and Katz, A. (2004) Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann. Intern. Med. 140, 533–7. First citation in articleCrossrefGoogle Scholar

  • Benzie, I.F. (2003) Evolution of dietary antioxidants. Comp.Biochem. Physiol. A. Mol. Integr. Physiol. 136, 113–26. First citation in articleCrossrefGoogle Scholar

  • Jackson, T.S., Xu, A., Vita, J.A. and Keaney, J.F. Jr. (1998) Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. Circ. Res. 83, 916–22. First citation in articleCrossrefGoogle Scholar

  • Suresh, M.V., Sreeranjit Kumar, C.V., Lal, J.J. and Indira, M. (1999) Impact of massive ascorbic acid supplementation on alcohol induced oxidative stress in guinea pigs. Toxicol. Lett. 104, 221–9. First citation in articleCrossrefGoogle Scholar

  • Turley, S.D., West, C.E., and Horton, B.J. (1976) The role of ascorbic acid in the regulation of cholesterol metabolism and in the pathogenesis of atherosclerosis. Atherosclerosis 24, 1–18. First citation in articleCrossrefGoogle Scholar

  • Lynch, S.M., Gaziano, J.M. and Frei, B. (1996) Ascorbic acid and atherosclerotic cardiovascular disease. Subcell. Biochem. 25, 331–67. First citation in articleCrossrefGoogle Scholar

  • Marcolin, E., Forgiarini, L.F., Tieppo, J., Dias, A.S., Freitas, L.A. and Marroni, N.P. (2011) Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis. Arq. Gastroenterol. 48, 72–9. First citation in articleCrossrefGoogle Scholar

  • Kim, N.H., Choi, S.K., Kim, S.J., Moon, P.D., Lim, H.S., Choi, I.Y., Na, H.J., An, H.J., Myung, N.Y., Jeong, H.J., Um, J.Y., Hong, S.H., Kim, H.M. (2008) Green tea seed oil reduces weight gain in C57BL/6J mice andinfluences adipocyte differentiation by suppressing peroxisome proliferator-activated receptor-γ. Pflugers. Arch. 457, 293–302. First citation in articleGoogle Scholar

  • Kleiner, D.E., Brunt, E.M., Van Natta, M., Behling, C., Contos, M.J.,Cummings, O.W.,Ferrell, L.D., Liu, Y.C., Torbenson, M.S., Unalp-Arida, A., Yeh, M., McCullough, A.J. and Sanyal, A.J. (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313–21. First citation in articleCrossrefGoogle Scholar

  • Cameron, E. and Pauling, L. (1993) Cancer and vitamin C, pp 100, Camino Books, Philadelphia. First citation in articleGoogle Scholar

  • Ishii, H., Kurose, I. and Kato, S. (1997) Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress. J. Gastroenterol. Hepatol. 12, S272–82. First citation in articleCrossrefGoogle Scholar

  • Abhilash, P.A., Harikrishnan, R. and Indira, M. (2012) Ascorbic acid supplementation causes faster restoration of reduced glutathione content in the regression of alcohol-induced hepatotoxicity in male guinea pigs. Redox. Rep. 17, 72–9. First citation in articleCrossrefGoogle Scholar

  • Abhilash, P.A., Harikrishnan, R. and Indira, M. (2013) Ascorbic acid is superior to silymarin in the recovery of ethanol-induced inflammatory reactions in hepatocytes of guinea pigs. J. Physiol. Biochem. 69, 785–98. First citation in articleCrossrefGoogle Scholar

  • Brunt, E.M. (2010) Pathology of nonalcoholic fatty liver disease. Nat. Rev. Gastroenterol. Hepatol. 7, 195–203. First citation in articleCrossrefGoogle Scholar

  • Oliveira, C.P., Gayotto, L.C., Tatai, C., Della Nina, B.I., Lima, E.S. and Abdalla, D.S. (2003) Vitamin C and vitamin E in prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in choline deficient diet fed rats. Nutr. J. 2, 9. First citation in articleGoogle Scholar

  • Ersöz, G., Günşar, F., Karasu, Z., Akay, S., Batur, Y. and Akarca, U.S. (2005) Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment. Turk. J. Gastroenterol. 16, 124–8. First citation in articleGoogle Scholar

  • Ued Fda, V. and Weffort, V.R. (2013) Antioxidant vitamins in the context of nonalcoholic fatty liver disease in obese children and adolescents. Rev. Paul. Pediatr. 31, 523–30. First citation in articleGoogle Scholar

  • Simom, J.A. (1992) Vitamin C and cardiovascular disease: a review. J. Am. Coll. Nutr. 11, 107–25. First citation in articleGoogle Scholar

  • Afkhami-Ardekani, M. and Shojaoddiny-Ardekani, A. (2007) Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian. J. Med. Res. 126, 471–4. First citation in articleGoogle Scholar