The relationship of fructose consumption with MDA levels in rat liver and its effect on the expression levels of COX-2 and NRF-2 genes

Abstract

The use of fructose as converted sugar in the food industry is quite common. Steatosis and degeneration occur due to the use of fructose in the liver where sugar is primarily metabolized. However, there is not enough information about the level of MDA and the expression levels of COX-2 and NRF-2 in the liver with low and high fructose consumption. The aim of the study is to evaluate the effect of different concentrations of fructose solutions on the expression levels of COX-2 and NRF-2 genes as well as MDA levels in the livers of rats. In this study, the effects of different fructose solution [F15; (15%) F30; (30%) and F60; (60%)] consumption for 10 weeks in rats on the MDA levels also COX-2 and NRF-2 genes expression levels in the liver were investigated. The MDA level and COX-2 gene expression level in F60 group were higher than the control and other groups (P<0.01). These findings suggest that MDA elevation in the liver may be due to inflammation. However, no change was observed in total NRF-2 gene expression. Also, a positive correlation was found between levels of COX-2 and NRF-2 expressions in F30 (0.965; P<0.01). These findings may be attributed to inflammation of liver. This may have been due to an increase in nuclear formation of NRF-2. As a result, the use of high concentration fructose solution has been found to increase the level of MDA in the liver due to inflammation.

Keywords

• COX-2,Fructose,Gene Expression,MDA,NRF-2

References

1. 1. Batista LO, Ramos VW, Rosas Fernández MA, et al (2019): Oral solution of fructose promotes SREBP-1c high-expression in the hypothalamus of Wistar rats. Nutr Neurosci, 22, 648-654.
2. 2. Bhutia Y, Ghosh A, Sherpa ML, et al (2011): Serum malondialdehyde level: Surrogate stress marker in the Sikkimese diabetics. J Nat Sc Biol Med, 2, 107-112.
3. 3. Bulut İK, Mir S (2011): Fruktoz ve böbrek hastalıkları. CMJ, 33, 499-507.
4. 4. de Moura RF, Ribeiro C, de Oliveira JA, et al (2008): Metabolic syndrome signs in Wistar rats submitted to different high-fructose ingestion protocols. Br J Nutr, 101, 1178-1184.
5. 5. Frungieri MB, Weidinger S, Meineke V, et al (2002): Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: possible relevance to human fibrotic disorders. Proc Natl Acad Sci, 99, 15072-15077.
6. 6. Girard A, Madani S, El Boustani ES, et al (2005): Changes in lipid metabolism and antioxidant defense status in spontaneously hypertensive rats and Wistar rats fed a diet enriched with fructose and saturated fatty acids. Nutrition, 21, 240-248.
7. 7. Güvenç M, Cellat M, Özkan H, et al (2019): Protective effects of tyrosol against DSS-induced ulcerative colitis in rats. Inflammation, 42, 1680-1691.
8. 8. Harper KA, Tyson-Capper AJ (2008): Complexity of COX-2 gene regulation. Biochem Soc Trans, 36, 543-545.

9. 9. Kaliman P, Álvarez-López MJ, Cosín-Tomás M, et al (2014): Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators. Psychoneuroendocrinology, 40, 96-107.
10. 10. Kang KW, Lee SJ, Kim, SG (2005): Molecular mechanism of nrf2 activation by oxidative stress. Antioxid. Redox Signal, 7, 1664-1673.
11. 11. Kegg Pathway (2019): Fluid shear stress and atherosclerosis Available at https://www.genome.jp/kegg-in/show_pathway?map=hsa05418&show_description=show (Accessed Nov 6, 2019)
12. 12. Livak KJ, Schmittgen TD (2001): Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 25, 402-408.
13. 13. Lowry OH, Rosebrough NJ, Farr AL, et al (1951): Protein measurement with the folin phenol reagent. JBC, 193, 265-275.
14. 14. Ma Q (2013): Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol, 53, 401-426.
15. 15. Miyazaki M, Dobrzyn A, Man WC, et al (2004): Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and-independent mechanisms. J Biol Chem, 279, 25164-25171.
16. 16. Monzavi-Karbassi B, Hine RJ, Stanley JS, et al (2010): Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells. Int J Oncol, 37, 615-622.
17. 17. Nakkeeran M, Priasamy S, Inmozhi SR, et al (2017): Increased levels of inflammatory marker hsCRP, MDA and lipid profile in non-obese hypertension subjects. Biochem Anal Biochem, 6, 2161-2165.
18. 18. Özcan O, Erdal H, Çakırca G, et al (2015): Oksidatif stres ve hücre içi lipit, protein ve DNA yapıları üzerine etkileri. JCEI, 6, 331-336.
19. 19. Özkan H, Yakan A (2019): Dietary high calories from sunflower oil, sucrose and fructose sources alters lipogenic genes expression levels in liver and skeletal muscle in rats. Ann Hepatol, 18, 715-724.
20. 20. Pasko P, Barton H, Zagrodzki P, et al (2010): Effect of diet supplemented with quinoa seeds on oxidative status in plasma and selected tissues of high fructose-fed rats. Plant Food Hum Nutr, 65, 146-151.
21. 21. Roelofs HM, Te Morsche RH, van Heumen BW, et al (2014): Over-expression of COX-2 mRNA in colorectal cancer. BMC Gastroenterol, 14, 1-6.
22. 22. Santos BPd, da Costa Diesel LF, da Silva Meirelles L, et al (2001): Identification of suitable reference genes for quantitative gene expression analysis in rat adipose stromal cells induced to trilineage differentiation. Gene, 594, 211-219.
23. 23. Sharma RA, Gescher A, Plastaras JP, et al (2001): Cyclooxygenase-2, malondialdehyde and pyrimidopurinone adducts of deoxyguanosine in human colon cells. J Carcinog, 22, 1557-1560.
24. 24. Suzuki K, Islam KN, Kaneto H, et al (2000): The contribution of fructose and nitric oxide to oxidative stress in hamster islet tumor (HIT) cells through the inactivation of glutathione peroxidase. Electrophoresis: Int J, 21, 285-288.
25. 25. Wasowicz W, Neve J, Peretz A (1993): Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem, 39, 2522-2526.
26. 26. Zhang H, Li Y, Hu J, et al (2015): Effect of creosote bush-derived NDGA on expression of genes involved in lipid metabolism in liver of high-fructose fed rats: relevance to NDGA amelioration of hypertriglyceridemia and hepatic steatosis. PLoS One, 10, 1-21.
27. 27. Zhang HF, Shi LJ, Song GY, et al (2013): Protective effects of matrine against progression of high-fructose diet-induced steatohepatitis by enhancing antioxidant and anti-inflammatory defences involving Nrf2 translocation. Food Chem Toxicol, 55, 70-77.