Effect of glutamine on liver injuries induced by intestinal ischemia-reperfusion in rats

Renata Hartmann, Francielli Licks, Elizângela Gonçalves Schemitt, Josieli Raskopf Colares, Juliana da Silva, Rosa Maria Moura, Gilmara Pandolfo Zabot, Henrique Sarubbi Fillmann, Norma Possa Marroni

Resumen


Introduction: Intestinal ischemia-reperfusion (I/R) injury may cause cell and tissue damage, reaching also other organs such as the liver. Because of the involvement of free radicals in I/R injury, treatment options with antioxidants have been studied and tested.

Objective: To evaluate the effect of glutamine (Gln) in the liver of animals with intestinal I/R injury.

Methods: We used 20 male Wistar rats divided into four groups: sham-operated (SO); glutamine + sham-operated (G+SO); intestinal ischemia-reperfusion (I/R); glutamine + intestinal ischemia-reperfusion (G+I/R). The superior mesenteric artery was clamped for 30 minutes and reperfused for 15 minutes. Gln (25 mg/kg/day) diluted in 1 ml of saline was administered intraperitoneally on the two days before I/R induction.

Results: Levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), lipid peroxidation
(LPO) and expressions of interleukin-6 (IL-6) and nuclear factor kappa B (NF-kB) showed a significant reduction in the G+I/R group as compared with the I/R group. The activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the levels of glutathione (GSH) showed an increase in the G+I/R group as compared with the I/R group.

Conclusion: Pretreatment with Gln reduced oxidative, tissue damage and showed a decrease expression of inflammatory mediators.


Palabras clave


DNA damage. Inflammation. Lipid peroxidation. Oxidative stress.

Texto completo:

PDF PDF (English)

Referencias


- Ozturk H, Terzi EH, Ozgen U, Duran A, Ozturk H. Lithospermic Acid and Ischemia/Reperfusion Injury of the Rat Small Intestine Prevention. Adv Clin Exp Med 2012; 21: 433-9.

- Mallick IH, Yang W, Winslet MC, Seifalian AM. Ischemia-reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 2004; 49: 1359-77.

- Cho SS, Rudloff I, Berger PJ, Irwin MG, Nold MF, Cheng W, et al. Remifentanil ameliorates intestinal ischemia-reperfusion injury. BMC Gastroenterol 2013; 13: 69.

- Akyıldız HY, Karabacak A, Akyüz M, Sözüer E, Akcan A. Effects of piperine in experimental intestinal ischemia reperfusion model in rats. Ulus Travma Acil Cerrahi Derg 2013; 19: 387-91.

– Yuan Y, Guo H, Zhang Y, Zhou D, Gan P, Liang DM, et al. Protective Effects of L-Carnitine on Intestinal Ischemia/Reperfusion Injury in a Rat Model. J Clin Med Res 2011; 3: 78-84.

- He GZ, Zhou KG, Zhang R, Wang YK, Chen XF. Impact of intestinal ischemia/reperfusion and lymph drainage on distant organs in rats. World J Gastroenterol 2012; 18: 7271-8.

- Zabot GP, Carvalhal GF, Marroni NP, Hartmann RM, da Silva VD, Fillmann HS. Glutamine prevents oxidative stress in a model of mesenteric ischemia and reperfusion. World J Gastroenterol 2014; 20: 11406-14.

- Chassaing B, Etienne-Mesmin L, Gewirtz AT. Microbiota-liver axis in hepatic disease. Hepatology 2014; 59: 328-39.

- Ren Z, Cui G, Lu H, Chen X, Jiang J, Liu H, et al. Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats throught 16s rDNA-based analysis of microbial structure shift. PLoS One 2013; 8: e75950.

- Sasaki M, Joh T. Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant, protective agents. J Clin Biochem Nutr 2007; 40: 1-12.

- Ma L, Wang G, Chen Z, Li Z, Yao J, Zhao H, et al. Modulating the p66shc signaling pathway with protocatechuic acid protects the intestine from ischemia-reperfusion injury and alleviates secondary liver damage. ScientificWorldJournal 2014; 2014: 387640.

- Onder A, Kapan M, Gümüş M, Yüksel H, Böyük A, Alp H, et al. The protective effects of curcumin on intestine and remote organs against mesenteric ischemia/reperfusion injury. Turk J Gastroenterol 2012; 23: 141-7.

- Wu S, Zhu X, Jin Z, Tong X, Zhu L, Hong X, et al. The protective role of montelukast against intestinal ischemia-reperfusion injury in rats. Sci Rep. 2015; 5:15787.

- Fillmann H, Kretzmann NA, San-Miguel B, Llesuy S, Marroni N, González-Gallego J, et al. Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates the nuclear factor kappaB pathway in an experimental model of colitis in the rat. Toxicology 2007; 236: 217-26.

- Marques C, Mauriz JL, Simonetto D, Marroni CA, Tuñon MJ, González-Gallego J, et al. Glutamine prevents gastric oxidative stress in an animal model of portal hypertension gastropathy. Ann Hepatol 2011 10: 531-9.

- Neu J, Li N. Pathophysiology of glutamine and glutamate metabolism in premature infants. Curr Opin Clin Nutr Metab Care 2007; 10: 75-9.

- Sözen S, Kisakürek M, Yildiz F, Gönültas M, Dincel AS. The effects of glutamine on hepatic ischemia reperfusion injury in rats. Hippokratia 2011; 15: 161-6.

- Zhang WX, Zhou LF, Zhang L, Bao L, Wang CC, Meng HY, et al. Protective effects of glutamine preconditioning on ischemia-reperfusion injury in rats. Hepatobiliary Pancreat Dis Int 2011; 10: 78-82.

- Goldim JR, Raymundo MM. Pesquisa em saúde e direitos dos animais. 2 nd edn. Porto Alegre: HCPA; 1997.

- Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the care and use of laboratory animals. 8th ed. Washington, D.C.: THE NATIONAL ACADEMIES PRESS; 2011.

- Llesuy SF, Milei J, Molina H, Boveris A, Milei S. Comparison of lipid peroxidation and myocardial damage induced by adriamycin and 4'-epiadriamycin in mice. Tumori 1985; 71: 241-9.

- Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978; 52: 302–10.

- Speit G, Hartmann A. The comet assay (single-cell gel test). A sensitive genotoxicity test for the detection of DNA damage and repair. Methods Mol Biol 1999; 113: 203-12.

- Picada JN, Flores DG, Zettler CG, Marroni NP, Roesler R, Henriques JA. DNA damage in brain cells of mice treated with an oxidized form of apomorphine. Brain Res Mol Brain Res 2003; 114: 80-5.

Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 1973; 134: 707–716.

- Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. World J Biol Chem 1972; 247: 3170–5.

- Flohé L, Beckmann R, Giertz H, Loschen G. Oxygen-centered free radicals as mediators of inflammation. In: Oxidative Stress. London: Academic; 1985. p. 403–36.

- Beutler E, Duron O, Kelly BM. Improved method for determination of blood glutathione. J Lab Clin Med 1963; 61: 802–8.

- Laemmli U, Molbert E, Showe M, Kellenberger E. Form determining function of the genes required for the assembly of the head of bacteriophage T4. J Mol Biol, 1970 Apr; 49:99-113.

- Towbin H, Staehelin T, Gordon J. Eletrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Biotechnology. 1992;24:145-9.

- Liu J, Pan G, Liang T, Huang P. HGF/c-Met signaling mediated mesenchymal stem cell-induced liver recovery in intestinal ischemia reperfusion model. Int J Med Sci 2014; 11: 626-33.

- Inan M, Uz YH, Kizilay G, Topcu-Tarladacalisir Y, Sapmaz-Metin M, Akpolat M, et al. Protective effect of sildenafil on liver injury induced by intestinal ischemia/reperfusion. J Pediatr Surg 2013; 48: 1707-15.

- Jing H, Shen G, Wang G, Zhang F, Li Y, Luo F, et al. MG132 alleviates liver injury induced by intestinal ischemia/reperfusion in rats: involvement of the AhR and NFκB pathways. J Surg Res 2012; 176: 63-73.

- Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012; 24: 981-90.

- Shafik AN. Febuxostat improves the local and remote organ changes induced by intestinal ischemia/reperfusion in rats. Dig Dis Sci 2013; 58: 650-9.

- Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Cordero-Pérez P, Alarcón-Galván G, Torres-Gonzalez L, Muñoz-Espinosa LE, et al. Comparative effects of trislusal, S-adenosylmethionine, and dextromethorphan over intestinal ischemia/reperfusion injury. ScientificWorldJournal 2011; 11: 1886-92.

- Oliveira RJ, Sassaki ES, Monreal AC, Monreal MT, Pesarini JR, Mauro MO, et al. Pre-treatment with glutamine reduces genetic damage due to cancer treatment with cisplatin. Genet Mol Res 2013; 12: 6040-51.

- Sukhotnik I, Pollak Y, Coran AG, Pilatov J, Bejar J, Mogilner JG, et al. Glutamine attenuates the inhibitory effect of methotrexate on TLR signaling during intestinal chemotherapy-induced mucosistis in a rat. Nutr Metab (Lond) 2014; 11: 17.

- Zhao HD, Zhang F, Shen G, Li YB, Jing HR, Ma LF, et al. Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-AREpathway. World J Gastroenterol 2010; 16: 3002-10.

- Yao JH, Zhang XS, Zheng SS, Li YH, Wang LM, Wang ZZ, et al. Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion. World J Gastroenterol 2009; 15: 3240-45.




DOI: http://dx.doi.org/10.20960/nh.643

Enlaces refback

  • No hay ningún enlace refback.