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http://dx.doi.org/10.15616/BSL.2022.28.2.101

Histological Analysis of Hepatic Steatosis, Inflammation, and Fibrosis in Ascorbic Acid-Treated Ovariectomized Mice  

Lee, Mijeong (Department of Biomedical Engineering, Mokwon University)
Jeon, Suyeon (Department of Biomedical Engineering, Mokwon University)
Lee, Jungu (Department of Biomedical Engineering, Mokwon University)
Lee, Dongju (Department of Biomedical Engineering, Mokwon University)
Yoon, Michung (Department of Biomedical Engineering, Mokwon University)
Publication Information
Biomedical Science Letters / v.28, no.2, 2022 , pp. 101-108 More about this Journal
Abstract
High-fat diet (HFD)-fed ovariectomized (OVX) female mice were used as an animal model of obese postmenopausal women. We investigated the effects of ascorbic acid on the histological changes induced in the liver. Plasma alanine aminotransferase levels and liver weights were higher in mice fed an HFD for 18 weeks than in mice fed a low-fat diet, effects that were inhibited by ascorbic acid. Similarly, mice fed an ascorbic acid-supplemented HFD had less hepatic lipid accumulation than did mice fed an HFD alone. Moreover, administration of ascorbic acid reduced inflammatory cells, including mast cells and CD68-positive cells, and inflammatory foci in the liver and inhibited hepatocyte ballooning. Hepatic collagen levels were lower in ascorbic acid-treated versus non-treated mice. These results suggest that ascorbic acid inhibits hepatic steatosis, inflammation, and fibrosis in obese OVX mice. Thus, ascorbic acid intake may be useful for postmenopausal women with nonalcoholic fatty liver disease.
Keywords
Ascorbic acid; Ovariectomized mouse; Liver; Steatosis; Inflammation; Fibrosis;
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1 Asokan SM, Wang T, Wang MF, Lin WT. A novel dipeptide from potato protein hydrolysate augments the effects of exercise training against high-fat diet-induced damages in senescence-accelerated mouse-prone 8 by boosting pAMPK/SIRT1/PGC-1α/pFOXO3 pathway. Aging. 2020. 12: 7334.   DOI
2 Bahadoran Z, Golzarand M, Mirmiran P, Shiva N, Azizi F. Dietary total antioxidant capacity and the occurrence of metabolic syndrome and its components after a 3-year follow-up in adults: Tehran Lipid and Glucose Study. Nutr Metab. 2012. 9: 70.   DOI
3 Caldwell S, Ikura Y, Dias D, Isomoto K, Yabu A, Moskaluk C, Pramoonjago P, Simmons W, Scruggs H, Rosenbaum N, Wilkinson T, Toms P, Argo CK, Al-Osaimi AM, Redick JA. Hepatocellular ballooning in NASH. J Hapatol. 2010. 53: 719-723.   DOI
4 Canoy D, Wareham N, Welch A, Bingham S, Luben R, Day N, Khaw KT. Plasma ascorbic acid concentrations and fat distribution in 19,068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study. Am J Clin Nutr. 2005. 82: 1203-1209.   DOI
5 Clark JM. The Epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol. 2006. 40: S5-S10.   DOI
6 Erickson SK. Nonalcoholic fatty liver disease. J Lipid Res. 2009. 50: S412-S416.   DOI
7 Gao Y, Liu Y, Yang M, Guo X, Zhang M, Li H, Zhao J. IL-33 treatment attenuated diet-induced hepatic steatosis but aggravated hepatic fibrosis. Oncotarget. 2016. 7: 33649.   DOI
8 Quinn MA, Xu X, Ronfani M, Cidlowski JA. Estrogen deficiency promotes hepatic steatosis via a glucocorticoid receptordependent mechanism in mice. Cell Rep. 2018. 22: 2690-2701.   DOI
9 Senen D, Adanali G, Ayhan M, Gorgu M, Erdogan B. Contribution of vitamin C administration for increasing lipolysis. Aesthetic Plast Surg. 2002. 26: 123-125.   DOI
10 Tai HC, Chung SD, Chien CT, Yu HJ. Sulforaphane improves ischemia-induced detrusor overactivity by downregulating the enhancement of associated endoplasmic reticulum stress, autophagy, and apoptosis in rat bladder. Sci Rep. 2016. 6: 1-16.   DOI
11 Wang SW, Sheng H, Bai YF, Weng YY, Fan XY, Lou LJ, Zhang F. Neohesperidin enhances PGC-1α-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice. Nutr Diabetes. 2020. 10: 1-11.   DOI
12 Wu K, Huang R, Wu H, Liu Y, Yang C, Cao S, Hou X, Chen B, Dal, J, Wu C. Collagen-binding vascular endothelial growth factor attenuates CCl4-induced liver fibrosis in mice. Mol Med Rep. 2016. 14: 4680-4686.   DOI
13 Song HM, Li X, Liu YY, Lu WP, Cui ZH, Zhou L, Yao D, Zhang HM. Carnosic acid protects mice from high-fat diet-induced NAFLD by regulating MARCKS. Int J Mol Med. 2018. 42: 193-207.
14 Jeftic I, Jovicic N, Pantic J, Arsenijevic N, Lukic ML, Pejnovic N. Galectin-3 ablation enhances liver steatosis, but attenuates inflammation and IL-33-dependent fibrosis in obesogenic mouse model of nonalcoholic steatohepatitis. Mol Med. 2015. 21: 453-465.   DOI
15 Campion J, Milagro FI, Fernandez D, Martinez JA. Differential gene expression and adiposity reduction induced by ascorbic acid supplementation in a cafeteria model of obesity. J Physiol Biochem. 2006. 62: 71-80.   DOI
16 Garcia-Diaz D, Campion J, Milagro FI, Martinez JA. Adiposity dependent apelin gene expression: relationships with oxidative and inflammation markers. Mol Cell Biochem. 2007. 305: 87-94.   DOI
17 Hong J, Stubbins RE, Smith RR, Harvey AE. Nunez NP. Differential susceptibility to obesity between male, female and ovariectomized female mice. Nutr J. 2009. 8: 11.   DOI
18 Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010. 51: 1972-1978.   DOI
19 Cai X, Wang J, Wang J, Zhou Q, Yang B, He Q, Weng Q. Intercellular crosstalk of hepatic stellate cells in liver fibrosis: New insights into therapy. Pharmacol Res. 2020. 155: 104720.   DOI
20 Garcia-Diaz DF, Lopez-Legarrea P, Quintero P, Martinez JA. Vitamin C in the treatment and/or prevention of obesity. J Nutr Sci Vitaminol. 2014. 60: 367-379.   DOI
21 Jun SC, Jung EY, Kang DH, Kim JM, Chang UJ, Suh HJ. Vitamin C increases the fecal fat excretion by chitosan in guinea-pigs, thereby reducing body weight gain. Phytother Res. 2010. 24: 1234-1241.   DOI
22 Khashab MA, Liangpunsakul S, Chalasani N. Nonalcoholic fatty liver disease as a component of the metabolic syndrome. Curr. Gastroenterol Rep. 2008. 10: 73-80.   DOI
23 Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, UnalpArida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005. 41: 1313-1321.   DOI
24 Koyama Y, Brenner DA. Liver inflammation and fibrosis. J Clin Invest. 2017. 127: 55-64.   DOI
25 Nishio E, Hayashi T, Nakatani M, Aida N, Suda R, Fujii T, Wakatsuki T, Honda S, Harada N, Shimono Y. Lack of association of ovariectomy-induced obesity with overeating and the reduction of physical activities. Biochem Biophys Rep. 2019. 20: 100671.   DOI
26 Van Herck MA, Vonghia L, Francque SM. Animal models of nonalcoholic fatty liver disease-a starter's guide. Nutrients, 2017. 9: 1072.   DOI
27 Matsumoto M, Hada N, Sakamaki Y, Uno A, Shiga T, Tanaka C, Ito T, Katsume A, Sudoh M. An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. Int J Exp Pathol. 2013. 94: 93-103.   DOI
28 Neuschwander-Tetri BA. Non-alcoholic fatty liver disease. BMC Med. 2017. 15: 1-6.   DOI
29 Onyekwere CA, Ogbera AO, Samaila AA, Balogun BO, Abdulkareem FB. Nonalcoholic fatty liver disease: Synopsis of current developments. Niger J Clin Pract. 2015. 18: 703-712.   DOI
30 Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021. 397: 2212-2224.   DOI
31 Rezazadeh A, Yazdanparast R. Prevention of nonalcoholic steatohepatitis in rats by two manganese-salen complexes. Iran Biomed J. 2014. 18: 41-48.
32 Sarwar R, Pierce N, Koppe S. Obesity and nonalcoholic fatty liver disease: current perspectives. Diabetes Metab Syndr Obes. 2018. 11: 533-542.   DOI
33 Schwabe RF, Tabas I, Pajvani UB. Mechanisms of fibrosis development in nonalcoholic steatohepatitis. Gastroenterology. 2020. 158: 1913-1928.   DOI
34 Lee H, Ahn J, Shin SS, Yoon M. Ascorbic acid inhibits visceral obesity and nonalcoholic fatty liver disease by activating peroxisome proliferator-activated receptor α in high-fat-dietfed C57BL/6J mice. Int J Obes. 2019. 43: 1620-1630.   DOI
35 Smith AK, Ropella GEP, McGill MR, Krishnan P, Dutta L, Kennedy RC, Jaeschke H, Hunt CA. Contrasting model mechanisms of alanine aminotransferase (ALT) release from damaged and necrotic hepatocytes as an example of general biomarker mechanisms. PLoS Comput Biol. 2020. 16: e1007622.   DOI
36 Johnston CS, Beezhold BL, Mostow B, Swan PD. Plasma vitamin C is inversely related to body mass index and waist circumference but not to plasma adiponectin in nonsmoking adults. J Nutr. 2007. 137: 1757-1762.   DOI