Main Article Content
Introduction: Fructose and hydrogenated oil are appeared together as ingredients in several processed food, in which consumption of those is a risk factor to develop metabolic diseases. Liver is a major organ which is impacted by these diets. Cytochrome P450 3A (CYP3A) is a major hepatic cytochrome P450 enzyme that takes responsible for metabolism of almost clinical drugs. The present study aimed to investigate hepatic histopathology and CYP3A11 pattern in mice fed with high fat- and high fructose-diet (HFFD). Methods: Seven-week-old male ICR mice (n=5) were intragastrically administered hydrogenated soybean oil (1 mL/day/mouse) with free access to 20% (w/v) aqueous fructose solution for 2, 4, and 8 weeks. The protein expression and catalytic activity of CYP3A11 were determined employing immunoblotting techniques and a specific reaction of erythromycin N-demethylation (ENDM), respectively. Results: Karyorrhexis and pyknosis of nuclei were detected after the HFFD feeding for 4 weeks while Kupffer cells in sinusoid and microvesicular hepatocytes were observed after 8 weeks of the induction. The change of hepatic histomorphological features was correlated with an increase in the protein level and catalytic activity of CYP3A11. Moreover, the HFFD-fed mice were increased in the fasting blood glucose level and AUC in the oral glucose tolerance test at the end of the study. Conclusion: High fat- and high fructose-consumption worsen the physiological feature of hepatic tissue along with induction of murine CYP3A11 profile, though it did not affect the weight gaining. Hence, a person with long-term consumption of high fat- and/or high fructose-diet has a risk of hepatic pathology and induction of CYP3A11 expression, leading to alter drug metabolism and extensive risk of drug interaction.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
In the case that some parts are used by others The author must Confirm that obtaining permission to use some of the original authors. And must attach evidence That the permission has been included
Baffy G. Kupffer cells in non-alcoholic fatty liver disease: the emerging view. J Hepatol 2009; 51(1): 212-223.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254.
Chatuphonprasert W, Jarukamjorn K. Impact of six fruits--banana, guava, mangosteen, pineapple, ripe mango and ripe papaya--on murine hepatic cytochrome P450 activities. J Appl Toxicol 2012; 32(12): 994-1001.
Chatuphonprasert W, Lao-Ong T, Jarukamjorn K. Improvement of superoxide dismutase and catalase in streptozotocin-nicotinamide-induced type 2-diabetes in mice by berberine and glibenclamide. Pharm Biol 2013; 52(4): 419-427.
de Castro UG, dos Santos RA, Silva ME, et al. Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats. Lipids Health Dis 2013; 12: 136.
Dostalek M, Hardy KD, Milne GL, et al. Development of oxidative stress by cytochrome P450 induction in rodents is selective for barbiturates and related to loss of pyridine nucleotide-dependent protective systems. J Biol Chem 2008; 283(25): 17147-17157.
Fisher CD, Lickteig AJ, Augustine LM, et al. Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab Dispos 2009; 37(10): 2087-2094.
Hart SN, Cui Y, Klaassen CD, Zhong XB. Three patterns of cytochrome P450 gene expression during liver maturation in mice. Drug Metab. Dispos. 2009; 37(1): 116-121.
Jarrar MH, Baranova A, Collantes R, et al. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 27(5): 412-421.
Jearapong N, Chatuphonprasert W, Jarukamjorn K. Effect of tetrahydrocurcumin on the profiles of drug-metabolizing enzymes induced by a high fat and high fructose diet in mice. Chem Biol Interact 2015; 239: 67-75.
Ju C, Tacke F. Hepatic macrophages in homeostasis and liver diseases: from pathogenesis to novel therapeutic strategies. Cell Mol Immunol 2016;13(3): 316-327.
Lim JS, Mietus-Snyder M, Valente A, Schwarz JM, Lustig RH. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol 2010; 7(5): 251-264.
Liu W, Baker RD, Bhatia T, Zhu L, Baker SS. Pathogenesis of nonalcoholic steatohepatitis. Cell Mol Life Sci 2016; 73(10): 1969-1987.
Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med 2008; 44(5): 723-738.
Minamiyama Y, Takemura S, Toyokuni S, et al. CYP3A induction aggravates endotoxemic liver injury via reactive oxygen species in male rats. Free Radic Biol Med 2004; 37(5): 703-712.
Nebert DW, Russell DW. Clinical importance of the cytochromes P450. Lancet 2002; 360(9340): 1155-1162.
Nomura K, Yamanouchi T. The role of fructose-enriched diets in mechanisms of nonalcoholic fatty liver disease. J Nutr Biochem 2012; 23(3): 203-208.
Ouyang X, Cirillo P, Sautin Y, et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 2008; 48(6): 993-999.
Podrini C, Cambridge EL, Lelliott CJ, et al. High-fat feeding rapidly induces obesity and lipid derangements in C57BL/6N mice. Mamm Genome 2013; 24(5-6): 240-251.
Rolo AP, Teodoro JS, Palmeira CM. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic Biol Med 2012; 52(1): 59-69.
Tetri LH, Basaranoglu M, Brunt EM, Yerian LM, Neuschwander-Tetri BA. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol 2008; 295(5): G987-995.
Tillman EJ, Morgan DA, Rahmouni K, Swoap SJ. Three Months of High-Fructose Feeding Fails to Induce Excessive Weight Gain or Leptin Resistance in Mice. PLoS One 2014; 9(9):e107206.doi: 10.1371/ journal.pone.0107206
Weerawatanakorn M. Dicarbonyl compounds and sugar contents of Thai commercial beverages. Songklanakarin J Sci Technol 2013; 35(6): 631-639.
White JS, Hobbs LJ, Fernandez S. Fructose content and composition of commercial HFCS-sweetened carbonated beverages. Int J Obes (Lond) 2015; 39(1): 176-182.
Yang ZH, Miyahara H, Takeo J, Katayama M. Diet high in fat and sucrose induces rapid onset of obesity-related metabolic syndrome partly through rapid response of genes involved in lipogenesis, insulin signalling and inflammation in mice. Diabetol Metab Syndr 2012; 4(1): 32.
Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 2013; 138(1): 103-141.
Zivkovic AM, German JB, Sanyal AJ. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr 2007; 86(2): 285-300.