Effects of glutamine on oxidative stress and nuclear factor‑κB expression in the livers of rats with nonalcoholic fatty liver disease

Lin,Zhihui; Cai,Fangfang; Lin,Ning; Ye,Jinli; Zheng,Qiqi; Ding,Guisheng

doi:10.3892/etm.2013.1434

Effects of glutamine on oxidative stress and nuclear factor‑κB expression in the livers of rats with nonalcoholic fatty liver disease

Authors:
- Zhihui Lin
- Fangfang Cai
- Ning Lin
- Jinli Ye
- Qiqi Zheng
- Guisheng Ding
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Affiliations: Departments of Gastroenterology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Departments of Gastroenterology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Departments of Ultrasound, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Departments of Ultrasound, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
Published online on: December 4, 2013 https://doi.org/10.3892/etm.2013.1434
Pages: 365-370

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Abstract

The aim of this study was to investigate the effects of glutamine on the histomorphology of the liver, oxidative stress and nuclear factor‑κB (NF‑κB) expression in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD was induced in rats by a high‑fat diet, and rats in the treatment group were subjected to oral administration of glutamine (1 g/kg/day). Rats from the treatment, model and normal control groups were assessed after 8 and 12 weeks (n=6 per group at each time‑point). The levels of glutathione (GSH), malondialdehyde (MDA) and tumor necrosis factor‑α (TNF‑α) in the liver, and the liver histopathology and NF‑κB protein 65 (p65) expression in the liver were assessed. Compared with the control group under the same experimental period, the MDA and TNF‑α levels in the liver, the hepatic steatosis and the hepatic expression of NF‑κB p65 were significantly higher in the model and the treatment groups (P<0.05), while the GSH levels in the liver were significantly lower (P<0.05). These indices improved significantly in the treatment group compared with the model group (P<0.05). In conclusion, glutamine reduces the degree of oxidative stress in the liver, inhibits NF‑κB p65 expression and improves hepatic steatosis. Glutamine has a certain protective effect in NAFLD.

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1	Day CP: Non-alcoholic fatty liver disease: current concepts and management strategies. Clin Med. 6:19–25. 2006. View Article : Google Scholar : PubMed/NCBI
2	Yang S, Zhu H, Li Y, et al: Mitochondrial adaptations to obesity related oxidant stress. Arch Biochem Biophys. 378:259–268. 2000. View Article : Google Scholar : PubMed/NCBI
3	Madan K, Bhardwaj P, Thareja S, Gupta SD and Saraya A: Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD). J Clin Gastroenterol. 40:930–935. 2006. View Article : Google Scholar : PubMed/NCBI
4	Browning JD and Horton JD: Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 114:147–152. 2004. View Article : Google Scholar : PubMed/NCBI
5	Narasimhan S, Gokulakrishnan K, Sampathkumar R, et al: Oxidative stress is independently associated with non-alcoholic fatty liver disease (NAFLD) in subjects with and without type 2 diabetes. Clin Biochem. 43:815–821. 2010. View Article : Google Scholar : PubMed/NCBI
6	Stangl R, Szijártó A, Ónody P, et al: Reduction of liver ischemia-reperfusion injury via glutamine pretreatment. J Surg Res. 166:95–103. 2011. View Article : Google Scholar : PubMed/NCBI
7	Zhang WX, Zhou LF, Zhang L, et al: Protective effects of glutamine preconditioning on ischemia-reperfusion injury in rats. Hepatobiliary Pancreat Dis Int. 10:78–82. 2011. View Article : Google Scholar : PubMed/NCBI
8	Peng HC, Chen YL, Chen JR, et al: Effects of glutamine administration on inflammatory responses in chronic ethanol-fed rats. J Nutr Biochem. 22:282–288. 2011. View Article : Google Scholar : PubMed/NCBI
9	Kessel A, Toubi E, Pavlotzky E, et al: Treatment with glutamine is associated with down-regulation of Toll-like receptor-4 and myeloid differentiation factor 88 expression and decrease in intestinal mucosal injury caused by lipopolysaccharide endotoxaemia in a rat. Clin Exp Immunol. 151:341–347. 2008. View Article : Google Scholar
10	Kul M, Vurucu S, Demirkaya E, et al: Enteral glutamine and/or arginine supplementation have favorable effects on oxidative stress parameters in neonatal rat intestine. J Pediatr Gastroenterol Nutr. 49:85–89. 2009. View Article : Google Scholar : PubMed/NCBI
11	Tsai PH, Liu JJ, Chiu WC, Pai MH and Yeh SL: Effects of dietary glutamine on adhesion molecule expression and oxidative stress in mice with streptozotocin-induced type 1 diabetes. Clin Nutr. 30:124–129. 2011. View Article : Google Scholar : PubMed/NCBI
12	El-Sheikh NM and Khalil FA: L-arginine and L-glutamine as immunonutrients and modulating agents for oxidative stress and toxicity induced by sodium nitrite in rats. Food Chem Toxicol. 49:758–762. 2011. View Article : Google Scholar : PubMed/NCBI
13	Kim H: Glutamine as an immunonutrient. Yonsei Med J. 52:892–897. 2011. View Article : Google Scholar
14	Adams LA and Angulo P: Treatment of non-alcoholic fatty liver disease. Postgrad Med J. 82:315–322. 2006. View Article : Google Scholar : PubMed/NCBI
15	Yu JC, Jiang ZM and Li DM: Glutamine: a precursor of glutathione and its effect on liver. World J Gastroenterol. 5:143–146. 1999.PubMed/NCBI
16	Tihan DN, Erbil Y, Seven R, et al: The effect of glutamine on oxidative damage in an experimental abdominal compartment syndrome model in rats. Ulus Trauma Acil Cerrahi Derg. 17:1–8. 2011. View Article : Google Scholar : PubMed/NCBI
17	Park HJ, DiNatale DA, Chung MY, et al: Green tea extract attenuates hepatic steatosis by decreasing adipose lipogenesis and enhancing hepatic antioxidant defenses in ob/ob mice. J Nutr Biochem. 22:393–400. 2011. View Article : Google Scholar : PubMed/NCBI
18	Hardwick RN, Fisher CD, Canet MJ, Lake AD and Cherrington NJ: Diversity in antioxidant response enzymes in progressive stages of human nonalcoholic fatty liver disease. Drug Metab Dispos. 38:2293–2301. 2010. View Article : Google Scholar : PubMed/NCBI
19	Lee YM, Sutedja DS, Wai CT, et al: A randomized controlled pilot study of Pentoxifylline in patients with non-alcoholic steatohepatitis (NASH). Hepatol Int. 2:196–201. 2008. View Article : Google Scholar : PubMed/NCBI
20	Tilg H: The role of cytokines in non-alcoholic fatty liver disease. Dig Dis. 28:179–185. 2010. View Article : Google Scholar : PubMed/NCBI
21	Tsai PH, Yeh CL, Liu JJ, Chiu WC and Yeh SL: Effects of dietary glutamine on inflammatory mediator gene expressions in rats with streptozotocin-induced diabetes. Nutrition. 28:288–293. 2012. View Article : Google Scholar : PubMed/NCBI
22	Jang HJ, Kwak JH, Cho EY, et al: Glutamine induces heat-shock protein-70 and glutathione expression and attenuates ischemic damage in rat islets. Transplant Proc. 40:2581–2584. 2008. View Article : Google Scholar : PubMed/NCBI
23	Pai MH, Chien YW, Tsai YH, Hu YM and Yeh SL: Glutamine reduces the expression of leukocyte integrins leukocyte function-associated antigen-1 and macrophage antigen-1 in mice exposed to arsenic. Nutr Res. 28:544–549. 2008. View Article : Google Scholar : PubMed/NCBI
24	Kaplowitz N and Tsukamoto H: Oxidative stress and liver disease. Prog Liver Dis. 14:131–159. 1996.PubMed/NCBI
25	Videla LA, Tapia G, Rodrigo R, et al: Liver NF-kappa B and AP-1 DNA binding in obese patients. Obesity (Silver Spring). 17:973–979. 2009. View Article : Google Scholar : PubMed/NCBI
26	Dela Peña A, Leclercq I, Field J, George J, Jones B and Farrell G: NF-kappaB activation, rather than TNF, mediates hepatic inflammation in a murine dietary model of steatohepatitis. Gastroenterology. 129:1663–1674. 2005.PubMed/NCBI
27	Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J and Shoelson SE: Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 11:183–190. 2005. View Article : Google Scholar : PubMed/NCBI
28	Singleton KD, Beckey VE and Wischmeyer PE: Glutamine prevents activation of NF-kappa B and stress kinase pathways, attenuates inflammatory cytokine release, and prevents acute respiratory distress syndrome (ARDS) following sepsis. Shock. 24:583–589. 2005. View Article : Google Scholar
29	Singleton KD and Wischmeyer PE: Glutamine’s protection against sepsis and lung injury is dependent on heat shock protein 70 expression. Am J Physiol Regul Integr Comp Physiol. 292:R1839–R1845. 2007.
30	Huang Y, Li N, Liboni K and Neu J: Glutamine decreases lipopolysaccharide-induced IL-8 production in Caco-2 cells through a non-NF-kappaB p50 mechanism. Cytokine. 22:77–83. 2003. View Article : Google Scholar : PubMed/NCBI
31	Fan JG, Qian Y, Zheng XY, Cai XB and Lu YS: Effects of pentoxifyiline on hepatic nuclear factor-kappa B signaling pathway and insulin resistance in nonalcoholic steatohepatitis rats induced by fat-rich diet. Zhonghua Gan Zang Bing Za Zhi. 14:762–766. 2006.(In Chinese).