Solanum Fruit Juice as a Natural and Sustainable Source of Antioxidants for Patients with Chronic Hepatitis C under Antiviral Therapy
Abstract
Variations in liver metabolism as a result of hepatitis C virus have been established by numerous clinical trials. The use of antioxidants supplements has been reported to minimize the implication of this disease. In this regard, we examined the suitability of Solanum fruit juice, a natural source of vitamin C and citrus flavoniod as a precursor for the treatment of patients with chronic hepatitis C. Forty adult patients who were diagnosed with chronic hepatitis C and were under antiviral therapy were divided into two equal groups. Group 1 patients received their antiviral therapy with normal food and water and served as the control group while patients in group 2 were supplemented with Solanum fruit juice for eight consecutive weeks. Measurements for Anthropometric data, C reactive protein (CRP), atherogenic indices, biochemical parameters and activities of liver marker enzymes were recorded before and after eight weeks. No alterations were found in waist circumference, body mass and body fat following regular use of Solanum fruit juice. The serum levels of oxidative stress markers, LDL-cholesterol, total cholesterol, CRP and atherogenic indices decreased in the Solanum fruit juice group when compared to the control group. Moreover, the activities of the liver marker enzyme AST decreased in those who had high levels before the intervention. These results underscore the benefits of Solanum fruit juice in the diet of patients with HCV as a result of decreased cholesterol in blood serum, decreased inflammation, and increase in antioxidant capacity as well as maintaining body mass index. This clinical trial is registered at Pan African Clinical Trial Registry (www.pactr.org) with unique identification number PACTR201802003092138.
References
Rosen HR. Chronic hepatitis C infection. N Engl J Med. 2011;77:2429–2438
El-Zayadi A-R, Anis M. Hepatitis C virus induced insulin resistance impairs response to antiviral therapy. World J Gastroenterol. 2012;18:212–224. DOI:10.3748/ wjg.v18.i3.212
Huang CF, Hsieh MY, Yang JF, et al. Serum hs-CRP was correlated with treatment response to pegylated interferon and ribavirin combination therapy in chronic hepatitis C patients. Hepatol Int. 2010;4:621–627. DOI:10.1007/s12072-010-9200-8
Bartenschlager R, Cosset F-L, Lohmann V. Hepatitis C virus replication cycle. J Hepatol. 2010;53:583–585.
Petit JM, Minello A, Duvillard L, et al. Cell surface expression of LDL receptor in chronic hepatitis C: correlation with viral load. Am J Physiol Endocrinol Metab. 2007;293:E416–E420. DOI:10.1152/ajpendo.00091.2007
Gonçalvesa, D., Limaa, C., Ferreiraa, P., Costab, P., Costac, A., Figueiredoc, W. and Cesara, T. Orange juice as dietary source of antioxidants for patients with hepatitis C under antiviral therapy. Food and Nutrition Research, 2017; 61, 1296675
Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61:77–87. DOI:10.1002/hep.27259
Lin CC, Yin MC. Vitamins B depletion, lower iron status and decreased antioxidative defense in patients with chronic hepatitis C treated by pegylated interferon alfa and ribavirin. Clin Nutr. 2009;28:34–38. DOI:10.1016/j. clnu.2008.09.003
Onyeike E.N., Monanu M.O., Okoye C.N., 2012. Changes in the blood lipid profile of wistar albino rats fed rich cholesterol diet. Ann Biol Res. 3(11), 5186-5191.
Murakami Y, Koyabu T, Kawashima A, et al. Zinc supplementation prevents the increase of transaminase in chronic hepatitis C patients during therapy with pegylated interferon α-2b and ribavirin. J Nutr Sci Vitaminol. 2007;53:213–218.
Farias MS, Budni P, Ribeiro CM, et al. Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients. Gastroenterol Hepatol. 2012;35:386–394. DOI:10.1016/j.gastrohep.2012.03.004
Friedewald, W. T., Levy, R.I. and Friedrickson, D.S. Estimation of the Concentration of Low- Density Lipoprotein Cholesterol in Plasma, without use of the Preparative Ultracentrifuge. Clinical Chemistry, 1972; 18: (6), 499-502.
Matthews DR, Hosker JP, Rudenski AS, et al.Homeostasis model assessment: insulin resistanceand β-cell function from fasting plasma glucose andinsulin concentration in man. Diabetologia.1985;23:412–419.
Janaszewska A, Bartosz G. Assay of total antioxidant capacity: comparison of four methods as applied to human blood plasma. Scand J Clin Lab Invest. 2002;62:231–236.
Yagi K. Simple assay for the level of total lipid peroxides in serum or plasma. Methods Mol Biol. 1998;108:101– 106.
Ikewuchi, J. C. and Ikewuchi, C. C. Alteration of Plasma Lipid Profiles and Atherogenic Indices by Stachytarpheta jamaicensis L. (Vahl). Biokemistri, 2009; 21: (2), 71-77.
Huisman EJ, van Hoek B, van Soest H, et al. Preventive versus “on-demand” nutritional support during antiviral treatment for hepatitis C: a randomized controlled trial. J Hepatol. 2012;57:1069–1075. DOI:10.1016/j.jhep.2012.06.029
Panchal SK, Poudyal H, Iyer A, et al. High carbohydrate high fat diet-induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol.2011;57: 611–624. DOI:10.1097/FJC.0b013e31821b1379
Hourigan LF, Macdonald GA, Purdie D, et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology. 1999;29:1215–1219.
Siren R, Eriksson JG, Vanhanen H. Waist circumference a good indicator of future risk for type 2 diabetes and cardiovascular disease. BMC Public Health. 2012;12:631.DOI:10.1186/1471-2458-12-631
Jain SK, Pemberton PW, Smith A, et al. Oxidative stress sin chronic hepatitis C: not just a feature of late stage disease. J Hepatol. 2002;36:805–811.
Paracha UZ, Fatima K, Alqahtani M, et al. Oxidative stress and hepatitis C virus. Virol J. 2013;10:251.DOI:10.1186/1743-422X-10-251
Bandara P, George J, McCaughan G, et al. Antioxidant levels in peripheral blood, disease activity and fibrotic stage in chronic hepatitis C. Liver Int. 2005;25:518–526.DOI:10.1111/j.1478-3231.2005.01049.x
Lin CC, Yin MC. Vitamins B depletion, lower iron status and decreased antioxidative defense in patients with chronic hepatitis C treated by pegylated interferon alfa and ribavirin. Clin Nutr. 2009;28:34–38. DOI:10.1016/j.clnu.2008.09.003
Tirkey N, Pilkhwal S, Kuhad A, et al. Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney.BMC Pharmacology. 2005; 5:2. DOI:10.1186/1471-2210-5-2
Haidari F, Keshavarz SA, Rashidi MR, et al. Orangejuice and hesperidin supplementation to hyperuricemicrats alter oxidative stress markers and xanthine oxidoreductase activity. J Clin Biochem Nutr. 2009;45:285–291. DOI:10.3164/jcbn.09-15
Mendiratta S, Qu ZC, May JM. Erythrocyte ascorbate recycling: antioxidant effects in blood. Free Radic BiolMed. 1998;24:789–797.
Padayatty SJ, Katz A, Wang Y, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003;22:18–35.
Nimse SB, Pal D. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv. 2015;5:27986–28006.
May JM. Ascorbate function and metabolism in the human erythrocyte. Front Biosci. 1998; 3:d1–d10.
El-Zayadi A-R, Anis M. Hepatitis C virus induced insulin resistance impairs response to antiviral therapy. World J Gastroenterol. 2012; 18: 212–224. DOI:10.3748/wjg.v18.i3.212
Black S, Kushner I, Samols D. C-reactive protein. J Biol Chem. 2004; 279: 48487–48490.
Huang CF, Hsieh MY, Yang JF, et al. Serum hs-CRP was correlated with treatment response to pegylated interferon and ribavirin combination therapy in chronic hepatitis C patients. Hepatol Int. 2010;4:621–627.DOI:10.1007/s12072-010-9200-8
Devaraj S, Autret BC, Jialal I. Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers. Am J Clin Nutr.2006;84:756–761.
Franke AA, Cooney RV, Henning SM, et al. Bioavailability and antioxidant effects of orange juice components in humans. J Agric Food Chem.2005;53:5170–5178. DOI:10.1021/jf050054y
Nashaat EH. Lipid profile among chronic hepatitis C Egyptian patients and its levels pre and post treatment. Nat Sci. 2010;8:83–89.
Corey KE, Kane E, Munroe C, et al. Hepatitis C virus infection and its clearance alter circulating lipids: implications for long-term follow-up. Hepatology.2009;50:1030–1037. DOI:10.1002/hep.23219
Jorge PA, Neyra LC., Osaki RM., Almeida deE and Bragagnolo N. Effect of eggplant on plasma lipid levels, lipidic peroxidation and reversion of endothelial dysfuntion in experimental hyper- cholesterolemia. Arquivos Brasileiros de cadiologia. 1998; 70: 87-91.
Behall MD. Dietary fiber. Nutritional lessons for macronutrient substitutes. Annals of the Nork York Academy of sciences. 1997. 819: 142-154.
Edijala JK, Asagba SO, Eriyamremu GE and Atomatofa U. Parkistan journal of nutrition. 2003; 4(4): 245-249.
Yang W, Hood BL, Chadwick SL, et al. Fatty acid synthase is up-regulated during hepatitis C virus infection and regulates hepatitis C virus entry and production. Hepatology. 2008;48:1396–1403. DOI:10.1002/hep.22508
Wilcox LJ, Borradaile NM, Dreu LE, et al. Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. Lipid Res.2001;42:725–734.
Mullen W, Archeveque M-A, Edwards CA, et al. Bioavailability and metabolism of orange juice flavanones in humans: impact of a full-fat yogurt. J Agric Food Chem. 2008; 56: 11157–11164. DOI:10.1021/jf801974v
Silveira JQ, Cesar TB, Manthey JA, et al. Pharmacokinetics of flavanone glycosides after ingestion of single doses of fresh-squeezed orange juice versus commercially processed orange juice in healthy humans. J Agric Food Chem. 2014;62: 12576–12584. DOI: 10. 1021/jf5038163
Kanaze FI, Bounartzi MI, Georgarakis M, et al. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur J Clin Nutr.2007;61:472–477.
Kim HK, Jeong TS, Lee MK, et al. Lipid-lowering efficacy of hesperetin metabolites in high-cholesterol fed rats. Clin Chim Acta. 2003; 327:129–137.
Nahmias Y, Goldwasser J, Casali M, et al. ApolipoproteinB–dependent hepatitis C virus secretion is inhibited bythe grapefruit flavonoid naringenin. Hepatology.2008;47: 1437–1445. DOI:10.1002/hep.22197
Lee, Y.S., Yoon, S.K., Chung, E.S., Bae, S.H., Choi, J.Y., Han, J.Y., Chung, K.W., Sun, H.S., Kim, B.S. and Kim, B.K. (2001) The relationship of histologic activity to serum ALT, HCV genotype and HCV RNA titers in chronic hepatitis C. Journal of Korean Medical Science, 16, 585-591.
Dienstag, J.L. and Alter, H.J. (1986) Non-A, non-B hepatitis: Evolving epidemiologic and clinical perspective. Seminars in Liver Disease, 6, 67-81. doi:10.1055/s-2008-1040795
Tassopoulos, N.C. (1999) Treatment of patients with chronic hepatitis C and normal ALT levels. Journal of Hepatology, 31, 193-196. doi:10.1016/S0168-8278(99)80400-0
Kaur G, Tirkey N, Chopra K. Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity. Toxicology.2006;226:152–160. DOI:10.1016/j.tox.2006.06.018
Renugadevi J, Prabu SM. Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Exp Toxico lPathol. 2010;62:171–181. DOI:10.1016/j.etp.2009.03.010
Prabu SM, Shagirtha K, Renugadevi J. Naringenin in combination with vitamins C and E potentially protects oxidative stress-mediated hepatic injury in cadmium-intoxicated rats. J Nutr Sci Vitaminol.2011; 57:177–185.
Bin, W., Kai, L., Mantian, M. and Jian, W. Effect of Fruit Juice on Glucose Control and Insulin Sensitivity in Adults: A Meta-Analysis of 12 Randomized Controlled Trials. PLOS ONE, 2014; 9(4): e95323.
Liu, K., Xing, A. Chen, K., Wang, B., Zhou, R., et al. Effects of fruit juice on cholesterol and blood pressure in adults: a meta-analysis of 19 randomized controlled trials. PLOS ONE, 2013; 8:e61420.
Brehm A., Pfeiler G., Pacini G., Vierhapper H., Roden M. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Obesity. Clin Chem. 2004; 50(12), 2316–2322.
Usoro C.A.O., Adikwuru C.C., Usoro I.N., Nsonwu A.C. Lipid Profile of Postmenopausal Women in Calabar, Nigeria. Pak J Nutr. 2006; 5(1), 79-82.
Nwaichi, E. O. Osuoha, J. O. and Monanu, M. O. Nutraceutical Potential of Tetracarpidium conophorum and Buccholzia coriacea in Diet-induced Hyperlipidemia. Journal of Chemical Health Risks, 2017; 7 (3), 157–170.
