Alterations in oxidative metabolism in liver of female rats: Effects of long-term vitamin A deficiency

Orozco Reina Agustina; Agüero Rocio; Razzeto Gabriela; Gimenez Maria Sofia; Vasquez Gomez Miriam Ester

doi:10.30574/gscbps.2020.13.1.0064

Authors

Orozco Reina Agustina Department of Biochemistry and Biological Sciences, School of Chemistry, Biochemistry and Pharmacy, National University of San Luis, San Luis, Argentina.
Agüero Rocio Department of Biochemistry and Biological Sciences, School of Chemistry, Biochemistry and Pharmacy, National University of San Luis, San Luis, Argentina.
Razzeto Gabriela Department of Biochemistry and Biological Sciences, School of Chemistry, Biochemistry and Pharmacy, National University of San Luis, San Luis, Argentina.
Gimenez Maria Sofia Department of Biochemistry and Biological Sciences, School of Chemistry, Biochemistry and Pharmacy, National University of San Luis, San Luis, Argentina.
Vasquez Gomez Miriam Ester Department of Biochemistry and Biological Sciences, School of Chemistry, Biochemistry and Pharmacy, National University of San Luis, San Luis, Argentina.

DOI:

https://doi.org/10.30574/gscbps.2020.13.1.0064

Keywords:

Lipoperoxidation, Nitrotyrosine, Catalase, Superoxide dismutase, Nitric oxide synthetase

Abstract

Background: The latest estimate by 5 UN agencies is that 821 million people globally are undernourished, which puts them at risk of vitamin and other nutrient deficiencies. Vitamin A deficiency remains a widespread public health problem among women and children in the developing world the role of vitamin A and its active metabolites in pathways involved in antioxidant protection and in the inhibition of important pathways that promote oxidative stress.

Objectives: Determine if vitamin A deficiency could influence oxidative metabolism in 6-month-old female wistar rats.

Materials and Methods: Determine the concentration of carbonyl proteins, as a marker of protein oxidation; TBARS, as a lipoperoxidation marker; and nitrotyrosine as a marker of oxidative stress dependent on nitric oxide. Quantify the expression of CAT, SOD, eNOS and iNOS in the liver and wistar rats deficient in vitamin A for 6 months.

Results: An increase in the concentration of carbonyl protein and nitrotyrosine in the liver tissue deficient in vitamin A is observed. The expression of SOD, eNOS and iNOS decreased in the group with a private diet of vitamin A. From the regression analysis a positive correlation was established between hepatic retinoic acid levels and gene expression of eNOS, iNOS and SOD. A positive correlation between serum retinoic acid levels and gene expression of eNOS and iNOS was also observed.

Conclusions: It is possible to ratify the relationship between the development of stress and vitamin A levels; improving the understanding of hepatic metabolism and its response to the absence of this vitamin.

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References

Bailey RL, West KP Jr, Black RE. The epidemiology of global micronutrient deficiencies. Ann Nutr Metab. 2015; 66 (Suppl 2): 22–33.

Darnton-Hill I. Chapter 2, Prevalence, causes and consequences of micronutrient deficiencies. In Mannar V Hurrell R, editors. Food fortification in a globalized world. London, UK: Academic Press/Elsevier. 2017; 13–28.

FAO, IFAD, UNICEF, WFP, WHO. The state of food security and nutrition in the world [Internet]. Rome, Italy: Food and Agricultural Organization of the UN. 2018.

Darnton-Hill I. Public health aspects in the prevention and control of vitamin deficiencies. Curr Dev Nutr. N2019; 3(9): nzz075.

Klemm R, Palmer A, Greig A, Engle-Stone R and Dalmiya N. A changing landscape for vitamin a programs: implications for optimal intervention packages, program monitoring, and safety. Food and Nutrition Bulletin. 2016; 1-12.

Stephensen CB. Vitamin a, infection, and immune function. The Annua Review of Nutrition. 2001; 21: 167-192.

Rao AV, Rao LG. Carotenoids and human health. Pharmacol res. 2007; 55(3): 207-16.

Lo H W, F Ali-Osman. Genomic cloning of hGSTP1*C, an allelic human Pi class glutathione S-transferase gene variant and functional characterization of its retinoic acid response elements. J Biol Chem. 1997; 272(52): 32743-32749.

Ahlemeyer B, Bauerbach E, Plath M, Steuber M, Heers C, F Tegtmeier, J Krieglstein. Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level. Free Radic Biol Med. 2001; 30(10): 1067-1077.

Kartha VN, S. Krishnamurthy. Antioxidant function of vitamin A. Int J Vitam Nutr Res. 1977; 47(4): 394-401.

Melin AM, Carbonneau MA, Thomas MJ, Maviel MJ, Perromat A, Clerc M. Relationship between dietary retinol and alpha-tocopherol and lipid peroxidation in rat liver cytosol. Food Addit Contam. 1992; 9(1): 1-9.

Datta PK, Lianos EA. Retinoic acids inhibit inducible nitric oxide synthase expression in mesangial cells. Kidney Int. 1999; 56(2): 486-493.

Arroul-Lammali A, Rahal F, Chetouane R, Djeraba Z, Medjeber O, LadjouzeRezig A, Touil-Boukoffa C. Ex vivo all-trans retinoic acid modulates NO production and regulates IL-6 effect during rheumatoid arthritis: a study in Algerian patients. Immunopharmacol Immunotoxicol. 2017; 39(2): 87-96.

Gatica L, Alvarez S, Gomez N, Zago MP, Oteiza P, Oliveros L, Gimenez MS. Vitamin A deficiency induces prooxidant environment and inflammation in rat aorta. Free Radic Res. 2005; 39(6): 621-628.

Gatica LV, Oliveros LB, Pérez Díaz MF, Domínguez NS, Fornes MW, Gimenez MS. Implication of vitamin A deficiency on vascular injury related to inflammation and oxidative stress. Effects on the ultrastructure of rat aorta. Eur J Nutr. 2012; 51(1): 97-106.

Wiseman EM, Bar-El Dadon S, Reifen R. The vicious cycle of vitamin A deficiency: a review. Critical Reviews in Food Science and Nutrition. 2016; 57 (17): 3703–3714.

Anzulovich AC, Oliveros LB, Muñoz E, Martínez LD, Giménez MS. Nutritional deficiency alters antioxidant defenses and modifies the liver histoachitecture. J Trace Elem Exp Med. 2000; 13: 343-357.

Oliveros LB, Vega VA, Anzulovich AC, Ramírez DC, Giménez MS. Vitamin A deficiency modifies antioxidant defenses and essential element contents in rat heart. Nutr Res. 2000; 20: 1139-1150.

Vasquez Gomez ME, Varas S, Gimenez MS. Model of long-term vitamin a deficiency in the mammary gland of virgin rats. Open Access Library Journal. 2017; 4: e3887.

Neeld JB, Pearson WN. Macro and micro methods for the determination of vitamin A in serum using trifluoroacetic acid. Journal of Nutrition. 1963; 79: 454-462.

Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation, Methods Enzymol. 1990; 186: 421–431.

Winterbourn CC, Buss IH. Protein carbonyl measurement by enzyme-linked immunosorbent assay, Methods Enzymol. 1999; 300: 106–111.

Weber D, Kneschke N, Grimm S, Bergheim I, Breusing N, Grune T. Rapid and sensitive determination of protein-nitrotyrosine by ELISA: application to human plasma. Free Radic Res. 2012; 46: 276–285.

Puissant C, Houdebine LM. An improvement of the one-step method of RNA 29 isolation by extraction with guanidinium thiocyanate-phenol-chloroform acid. 30 Biotechniques. 1990; 8: 148-149.

Rossi WM, Garrido G, Núñez Sellés AJ. Biomarkers of oxidative stress in antioxidant therapy. Journal of Pharmacy & Pharmacognosy Research. 2016; 4(2): 62-83.

Weber D, Stuetz W, Bernhard W, Franz A, Raith M, Grune T, Breusing N. Oxidative stress markers and micronutrients in maternal and cord blood in relation to neonatal outcome. European Journal of Clinical Nutrition. 2014; 68: 215–222.

Tetik S, Kiliç A, Aksoy H, Rizaner N, Ahmad S, Yardimci T. Oxidative stress causes plasma protein modification. Indian J Exp Biol. 2015; 53(1): 25-30.

Granot E, Kohen R. Oxidative stress in abetalipoproteinemia patients receiving long-term vitamin E and vitamin A supplementation. The American Journal of Clinical Nutrition. 2004; 79 (2), 226–230.

de Oliveira MR. Review Article Vitamin A and Retinoids as Mitochondrial Toxicants. Oxidative Medicine and Cellular Longevity. 2015; Article ID 140267, 13.

Esteban-Pretel G, Marin MP, Renau-Piqueras J, Barber T, Timoneda J. Vitamin A deficiency alters rat lung alveolar basement membrane: reversibility by retinoic acid. J Nutr Biochem. 2010; 21(3), 227-236.

Barber T, Borras E, Torres L, Garcia C, Cabezuelo F, Lloret et al. Vitamin A deficiency causes oxidative damage to liver mitochondria in rats. Free Radic Biol Med. 2000; 29(1): 1-7.

Ravi Kumar S, Narayan B, Vallikannan B. Fucoxanthin restrains oxidative stress induced by retinol deficiency through modulation of Na(+)K(+)-ATPase [corrected] and antioxidant enzyme activities in rats. Eur J Nutr. 2008; 47(8): 432-441.

Sangeetha RK, Bhaskar N, Baskaran V. Comparative effects of beta-carotene and fucoxanthin on retinol deficiency induced oxidative stress in rats. Mol Cell Biochem. 2009; 331(1-2), 59-67.

Zhou D, Zaiger G, Ghebremeskel K, Crawford MA and Reifen R. Vitamin A deficiency reduces liver and colon docosahexaenoic acid levels in rats fed high linoleic and low alpha-linolenic acid diet. Prostaglandins Leukot Essent Fatty Acids. 2004; 71(6): 383-389.

Fonzo LS, Golini RS, Delgado SM, Ponce IT, Bonomi MR, Rezza IG, Anzulovich AC. Temporal patterns of lipoperoxidation and antioxidant enzymes are modified in the hippocampus of vitamin A-deficient rats. Hippocampus. 2009; 19(9): 869-880.

Azevedo PS, Minicucci MF, Chiuso-Minicucci F, Justulin LA, Matsubara LS, Matsubara BB, Paiva SA. Ventricular remodeling induced by tissue vitamin A deficiency in rats. Cell Physiol Biochem. 2010; 26(3), 395-402.

Li J, Cai X, Xia Q, Yao K, Chen J, Zhang Y, Wu Y. Involvement of endoplasmic reticulum stress in all-trans-retinal-induced retinal pigment epithelium degeneration. Toxicol Sci. 2015; 143(1), 196-208.

Zhao F, Wu T, Lau A, Jiang T, Huang Z, Wang XJ, Zhang DD. Nrf2 promotes neuronal cell differentiation. Free Radic Biol Med. 2009; 47(6): 867-879.

Tan KP, Kosuge K, Yang M, Ito S. NRF2 as a determinant of cellular resistance in retinoic acid cytotoxicity. Free Radic Biol Med. 2008; 45(12): 1663-1673.

James ML, Ross AC, Nicola T, Steele C, Ambalavanan N. VARA atenúa el desarrollo alveolar y la función pulmonar deteriorados inducidos por la hiperoxia en ratones recién nacidos. Am J Physiol Células Pulmonares Mol Physiol. 2013; 304 (11): L803 – L812.

Wang G, Xiu P, Li F, Xin C, Li K. Vitamin A supplementation alleviates extrahepatic cholestasis liver injury through Nrf2 activation. Oxid Med Cell Longev. 2014; 273692.

Balmus G, Karp NA, Ng BL, Jackson SP, Adams DJ, McIntyre RE. A high-throughput in vivo micronucleus assay for genome instability screening in mice. Nat Protoc. 2015; 10(1): 205-215.

Connelly L, Palacios-Callender M, Ameixa C, Moncada S, Hobbs AJ. Biphasic regulation of NF-kappa B activity underlies the pro- and anti-inflammatory actions of nitric oxide. J Immunol. 2001; 166(6): 3873-3881.

Gow A, Duran D, Thom SR, Ischiropoulos H. Carbon dioxide enhancement of peroxynitrite-mediated protein tyrosine nitration. Arch Biochem Biophys. 1996; 333: 42–48.

Beckman JS, Ye YZ, Anderson PG, Chen J, Accavitti MA, Tarpey MM et al. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe Seyler. 1994; 375: 81–88.

Kmieć Z. Cooperation of liver cells in health and disease. Berlin; New York, Springer. 2001.

Qiu H, Wu Y, Wang Q, Liu C, Xue L, Wang H, Jiang Q. Effect of berberine on PPARalpha-NO signalling pathway in vascular smooth muscle cell proliferation induced by angiotensin IV. Pharm Biol. 2007; 55(1): 227-232.

Vega VA, Anzulovich AC, Varas SM, Bonomi MR, Gimenez MS, Oliveros LB. Effect of nutritional vitamin A deficiency on lipid metabolism in the rat heart: Its relation to PPAR gene expression. Nutrition. 2009; 25(7-8): 828-838.