Effects of vitamin C supplementation on Chinese sausage-induced liver damage in rats
Main Article Content
Keywords
Chinese sausage, liver damage, metabolomics, N-nitrosodimethylamine, vitamin C
Abstract
Contamination of nitrosamine compounds in Chinese sausages and the relevant hepatoxicity have been reported. This study was conducted to evaluate the effects of vitamin C (VC) supplementation on Chinese sausage contaminated with N-nitrosodimethylamine (NDMA)-induced liver damage and relevant metabolomic changes. Rats were orally administered with Chinese sausage contaminated with NDMA at levels overpassing its safety limit. In some experiments, VC was additionally administered via drinking water to the rats for 25 weeks. Serum samples were collected from the rats for the measurement of the metabolomic profiles by using gas chromatography–mass spectrometry. Compared with the group administered with Chinese sausages alone, in rats with additional VC treatment, all serum biochemical parameters indicating hepatic damage were significantly alleviated, which suggested an improved hepatic function by VC supplementation. Metabonomic analysis of the serum samples showed notable changes in metabolites in VC-supplemented group as compared to that with sausage alone, especially for those involved in the regulation of amino acid or energy or lipid metabolism and/or anti-oxidative function. This study indicates that VC supplement in parallel with long-term exposure to Chinese sausage may attenuate liver damage and promote the recovery of liver function.
References
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Lbban, E., Ashor, A., Shannon, O.M., Idris, I. and Siervo, M., 2023. Is vitamin C a booster of the effects of dietary nitrate on endothelial function? Physiologic rationale and implications for research. Nutrition. 109: 111995. 10.1016/j.nut.2023.111995
Lee, H.S., 2019. Literature compilation of volatile N-nitrosamines in processed meat and poultry products—an update. Food Additives and Contaminants: Part A, Chemistry, Analysis, Control, Exposure and Risk Assessment. 36(10): 1491–1500. 10.1080/19440049.2019.1649472
Li, X., Bei, E., Qiu, Y., Xiao, H., Wang, J., Lin, P., et al., 2021. Intake of volatile nitrosamines by Chinese residents in different provinces via food and drinking water. Science of the Total Environment. 754: 142121. 10.1016/j.scitotenv.2020.142121
McCormick, W.J., 1954. Cancer: the preconditioning factor in pathogenesis; a new etiologic approach. Archives de Pédiatrie. 71(10): 313–322.
Miller, G.D., Nesbit, B.A., Kim-Shapiro, D.B., Basu, S. and Berry, M.J., 2022. Effect of vitamin C and protein supplementation on plasma nitrate and nitrite response following consumption of beetroot juice. Nutrients. 14(9): 1880. 10.3390/nu14091880
Monsen, E.R., 2000. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. National Academies Press, Washington (DC).
Myint, P.K., Luben, R.N., Welch, A.A., Bingham, S.A., Wareham, N.J. and Khaw, K.T., 2008. Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study. American Journal of Clinical Nutrition. 87(1): 64–69. 10.1093/ajcn/87.1.64
Nava Lauson, C.B., Tiberti, S., Corsetto, P.A., Conte, F., Tyagi, P., Machwirth, M., et al., 2023. Linoleic acid potentiates CD8(+) T cell metabolic fitness and antitumor immunity. Cell Metabolism. 35(4): 633–650. 10.1016/j.cmet.2023.02.013
Preddy, V.R., Watson, R.R. and Sherma, Z., 2010. Dietary components and immune function (Nutrition and Health). Humana Press, London, UK.
Qin, D.M., Wang, X.B., Zou, N., Han, C. and Xu, J., 2019. Gas chromatography-mass spectrometry (GC-MS) analysis of the volatile oil of Cichorium Glandulosum Boiss et Huet and its effects on carbon tetrachloride–induced liver fibrosis in rats. Medical Science Monitor. 25: 3591–3604. 10.12659/MSM.913445
Qiu, Y., Chen, J.H., Yu, W., Wang, P., Rong, M. and Deng, H., 2017. Contamination of Chinese salted fish with volatile N-nitrosamines as determined by QuEChERS and gas chromatography-tandem mass spectrometry. Food Chemistry. 232: 763–769. 10.1016/j.foodchem.2017.04.055
Rangel-Huerta, O.D. and Gil, A., 2016. Nutrimetabolomics: an update on analytical approaches to investigate the role of plant-based foods and their bioactive compounds in non-communicable chronic diseases. International Journal of Molecular Science. 17(12): 2072. 10.3390/ijms17122072
Rong, M., Wang, P., Qiu, Y., Liu, Y., Wang, Y. and Deng, H., 2018a. Effects of long-term intake of sausage with different content of NDMA on rat liver. Food Research and Development. 39(4): 168–174.
Rong, M., Wang, P., Qiu, Y., Liu, Y., Wang, Y. and Deng, H., 2018b. Metabolomic analysis of serum from rats following long-term intake of Chinese sausage. Food & Nutrition Research. 62: 1447. 10.29219/fnr.v62.1447
Sebedio, J.L., 2017. Metabolomics, nutrition, and potential biomarkers of food quality, intake, and health status. Advances in Food Nutrition Research. 82: 83–116. 10.1016/bs.afnr.2017.01.001
Shibutami, E. and Takebayashi, T., 2021. A scoping review of the application of metabolomics in nutrition research: the literature survey 2000–2019. Nutrients. 13(11): 3760. 10.3390/nu13113760
Simon, J.A., Hudes, E.S. and Tice, J.A., 2001. Relation of serum ascorbic acid to mortality among US adults. Journal of the American College of Nutrition. 20(3): 255–263. 10.1080/07315724.2001.10719040
Trygg, J., Holmes, E. and Lundstedt, T., 2007. Chemometrics in metabonomics. Journal of Proteome Research. 6(2): 469–479. 10.1021/pr060594q
Wu, G., Fang, Y.Z., Yang, S., Lupton, J.R. and Turner, N.D., 2004. Glutathione metabolism and its implications for health. Journal of Nutrition. 134(3): 489–492. 10.1093/jn/134.3.489
Zhao, Y., Zhang, H., Wu, X., Zhang, T., Shen, K., Li, L., et al., 2019. Metabonomic analysis of the hepatic injury suffer from hexavalent chromium poisoning in broilers. Environmental Science and Pollution Research International. 26(18): 18181–18190. 10.1007/s11356-019-05075-4
Zhao, Z., Wang, F., Chen, D. and Zhang, C., 2020. Red and processed meat consumption and esophageal cancer risk: a systematic review and meta-analysis. Clinical and Translational Oncology. 22(4): 532–545. 10.1007/s12094-019-02157-0
Adikwu, E. and Deo, O., 2013. Hepatoprotective effect of vitamin C (ascorbic acid). Pharmacology & Pharmacy. 4(1): 84–92.
Alarcon-Gil, J., Sierra-Magro, A., Morales-Garcia, J.A., Sanz-SanCristobal, M., Alonso-Gil, S., Cortes-Canteli, M., et al., 2022. Neuroprotective and anti-inflammatory effects of linoleic acid in models of Parkinson’s disease: the implication of lipid droplets and lipophagy. Cells. 11(15): 2297. 10.3390/cells11152297
Berends, J.E., van den Berg, L.M.M., Guggeis, M.A., Henckens, N.F.T., Hossein, I.J., de Joode, M., et al., 2019. Consumption of nitrate-rich beetroot juice with or without vitamin C supplementation increases the excretion of urinary nitrate, nitrite, and N-nitroso compounds in humans. International Journal of Molecular Science. 20(9): 2277. 10.3390/ijms20092277
Center, S.A., Erb, H.N. and Joseph, S.A., 1995. Measurement of serum bile acids concentrations for diagnosis of hepatobiliary disease in cats. Journal of the American Veterinary Medical Association. 207(8): 1048–1054.
Chain, E. P. o. C. i. t. F., Schrenk, D., Bignami, M., Bodin, L., Chipman, J. K., Del Mazo, J., et al., 2023. Risk assessment of N-nitrosamines in food. EFSA Journal. 21(3): e07884. 10.2903/j.efsa.2023.7884
Esmaeilizadeh, M., Hosseini, M., Beheshti, F., Alikhani, V., Keshavarzi, Z., Shoja, M., et al., 2020. Vitamin C improves liver and renal functions in hypothyroid rats by reducing tissue oxidative injury. International Journal for Vitamin and Nutrition Research. 90(1–2): 84–94. 10.1024/0300-9831/a000495
Frei, B., Birlouez-Aragon, I. and Lykkesfeldt, J., 2012. Authors’ perspective: what is the optimum intake of vitamin C in humans? Critical Reviews in Food Science and Nutrition. 52(9): 815–829. 10.1080/10408398.2011.649149
Fu, J., Wu, Z., Liu, J. and Wu, T., 2020. Vitamin C: a stem cell promoter in cancer metastasis and immunotherapy. Biomedicine and Pharmacotherapy. 131: 110588. 10.1016/j.biopha.2020.11058
Fu, Y., Xu, F., Jiang, L., Miao, Z., Liang, X., Yang, J., et al., 2021. Circulating vitamin C concentration and risk of cancers: a Mendelian randomization study. BMC Medicine. 19(1): 171. 10.1186/s12916-021-02041-1
Gu, C., Mao, X., Chen, D., Yu, B. and Yang, Q., 2019. Isoleucine plays an important role for maintaining immune function. Current Protein and Peptide Science. 20(7): 644–651. 10.2174/1389203720666190305163135
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans., 2018. Red Meat and Processed Meat. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 114. Lyon (France): International Agency for Research on Cancer.
Kauffmann, N., da Penha, L., Braga, D. V., Ataide, B.J.A., Mendes, N.S.F., de Sousa, L.P., et al., 2021. Differential effect of antioxidants glutathione and vitamin C on the hepatic injuries induced by Plasmodium berghei ANKA infection. BioMed Research International. 2021: 9694508. 10.1155/2021/9694508
Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., et al., 2021. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: results of a pilot clinical trial. Clinical and Translational Medicine. 11(3): e372. 10.1002/ctm2.372
Kumar, P., Osahon, O.W. and Sekhar, R.V., 2022. GlyNAC (glycine and N-acetylcysteine) supplementation in mice increases length of life by correcting glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormalities in mitophagy and nutrient sensing, and genomic damage. Nutrients. 14(5): 1114. 10.3390/nu14051114
Kumar, P., Osahon, O.W. and Sekhar, R.V., 2023. GlyNAC (glycine and N-acetylcysteine) supplementation in old mice improves brain glutathione deficiency, oxidative stress, glucose uptake, mitochondrial dysfunction, genomic damage, inflammation and neurotrophic factors to reverse age-associated cognitive decline: implications for improving brain health in aging. Antioxidants (Basel). 12(5): 1042. 10.3390/antiox12051042
Larsson, S.C., Mason, A.M., Vithayathil, M., Carter, P., Kar, S., Zheng, J.S., et al., 2022. Circulating vitamin C and digestive system cancers: Mendelian randomization study. Clinical Nutrition. 41(9): 2031–2035. 10.1016/j.clnu.2022.07.040
Lbban, E., Ashor, A., Shannon, O.M., Idris, I. and Siervo, M., 2023. Is vitamin C a booster of the effects of dietary nitrate on endothelial function? Physiologic rationale and implications for research. Nutrition. 109: 111995. 10.1016/j.nut.2023.111995
Lee, H.S., 2019. Literature compilation of volatile N-nitrosamines in processed meat and poultry products—an update. Food Additives and Contaminants: Part A, Chemistry, Analysis, Control, Exposure and Risk Assessment. 36(10): 1491–1500. 10.1080/19440049.2019.1649472
Li, X., Bei, E., Qiu, Y., Xiao, H., Wang, J., Lin, P., et al., 2021. Intake of volatile nitrosamines by Chinese residents in different provinces via food and drinking water. Science of the Total Environment. 754: 142121. 10.1016/j.scitotenv.2020.142121
McCormick, W.J., 1954. Cancer: the preconditioning factor in pathogenesis; a new etiologic approach. Archives de Pédiatrie. 71(10): 313–322.
Miller, G.D., Nesbit, B.A., Kim-Shapiro, D.B., Basu, S. and Berry, M.J., 2022. Effect of vitamin C and protein supplementation on plasma nitrate and nitrite response following consumption of beetroot juice. Nutrients. 14(9): 1880. 10.3390/nu14091880
Monsen, E.R., 2000. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. National Academies Press, Washington (DC).
Myint, P.K., Luben, R.N., Welch, A.A., Bingham, S.A., Wareham, N.J. and Khaw, K.T., 2008. Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study. American Journal of Clinical Nutrition. 87(1): 64–69. 10.1093/ajcn/87.1.64
Nava Lauson, C.B., Tiberti, S., Corsetto, P.A., Conte, F., Tyagi, P., Machwirth, M., et al., 2023. Linoleic acid potentiates CD8(+) T cell metabolic fitness and antitumor immunity. Cell Metabolism. 35(4): 633–650. 10.1016/j.cmet.2023.02.013
Preddy, V.R., Watson, R.R. and Sherma, Z., 2010. Dietary components and immune function (Nutrition and Health). Humana Press, London, UK.
Qin, D.M., Wang, X.B., Zou, N., Han, C. and Xu, J., 2019. Gas chromatography-mass spectrometry (GC-MS) analysis of the volatile oil of Cichorium Glandulosum Boiss et Huet and its effects on carbon tetrachloride–induced liver fibrosis in rats. Medical Science Monitor. 25: 3591–3604. 10.12659/MSM.913445
Qiu, Y., Chen, J.H., Yu, W., Wang, P., Rong, M. and Deng, H., 2017. Contamination of Chinese salted fish with volatile N-nitrosamines as determined by QuEChERS and gas chromatography-tandem mass spectrometry. Food Chemistry. 232: 763–769. 10.1016/j.foodchem.2017.04.055
Rangel-Huerta, O.D. and Gil, A., 2016. Nutrimetabolomics: an update on analytical approaches to investigate the role of plant-based foods and their bioactive compounds in non-communicable chronic diseases. International Journal of Molecular Science. 17(12): 2072. 10.3390/ijms17122072
Rong, M., Wang, P., Qiu, Y., Liu, Y., Wang, Y. and Deng, H., 2018a. Effects of long-term intake of sausage with different content of NDMA on rat liver. Food Research and Development. 39(4): 168–174.
Rong, M., Wang, P., Qiu, Y., Liu, Y., Wang, Y. and Deng, H., 2018b. Metabolomic analysis of serum from rats following long-term intake of Chinese sausage. Food & Nutrition Research. 62: 1447. 10.29219/fnr.v62.1447
Sebedio, J.L., 2017. Metabolomics, nutrition, and potential biomarkers of food quality, intake, and health status. Advances in Food Nutrition Research. 82: 83–116. 10.1016/bs.afnr.2017.01.001
Shibutami, E. and Takebayashi, T., 2021. A scoping review of the application of metabolomics in nutrition research: the literature survey 2000–2019. Nutrients. 13(11): 3760. 10.3390/nu13113760
Simon, J.A., Hudes, E.S. and Tice, J.A., 2001. Relation of serum ascorbic acid to mortality among US adults. Journal of the American College of Nutrition. 20(3): 255–263. 10.1080/07315724.2001.10719040
Trygg, J., Holmes, E. and Lundstedt, T., 2007. Chemometrics in metabonomics. Journal of Proteome Research. 6(2): 469–479. 10.1021/pr060594q
Wu, G., Fang, Y.Z., Yang, S., Lupton, J.R. and Turner, N.D., 2004. Glutathione metabolism and its implications for health. Journal of Nutrition. 134(3): 489–492. 10.1093/jn/134.3.489
Zhao, Y., Zhang, H., Wu, X., Zhang, T., Shen, K., Li, L., et al., 2019. Metabonomic analysis of the hepatic injury suffer from hexavalent chromium poisoning in broilers. Environmental Science and Pollution Research International. 26(18): 18181–18190. 10.1007/s11356-019-05075-4
Zhao, Z., Wang, F., Chen, D. and Zhang, C., 2020. Red and processed meat consumption and esophageal cancer risk: a systematic review and meta-analysis. Clinical and Translational Oncology. 22(4): 532–545. 10.1007/s12094-019-02157-0
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