Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

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Kusmiyati Tjahjono DK
Santoso Santoso
Dwi Ngestiningsih


BACKGROUND The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA) intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO) production and on necrosis of pancreatic beta cells. METHODS A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control), group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. RESULTS After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM). At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p= 0.000). No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25%) and moderate necrosis in group P2 (26-50%). CONCLUSION TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells

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DK, K. T., Santoso, S., & Ngestiningsih, D. (2013). Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats. Universa Medicina, 32(1), 51–59. - 59
Review Article


International Diabetes Federation Western Pasific Regional. Plan of action (2006-2010) for the western pacific declaration on diabetes: from evidence to action. Singapore: International Diabetes Federation Western Pasific Regional;2008.

Hu FB. Globalization of diabetes. The role of diet, lifestyle, and genes. Diabetes Care 2011; 34:1249 - 57.

Badan Penelitian dan Pengembangan Kesehatan Departemen Kesehatan, Republik Indonesia. Laporan nasional riset kesehatan dasar (Riskesdas). Jakarta: Badan Penelitian dan Pengembangan Kesehatan Departemen Kesehatan;2008.

Krishnan S, Coogan PF, Boggs DA, Rosenberg L, Palmer JR. Consumption of restaurant foods and incidence of type 2 diabetes in African American women. .Am J Clin Nutr 010;91:465-

Sartika RAD. Pengaruh asupan asam lemak trans terhadap profil lipid darah (disertasi). Jakarta: Fakultas Kesehatan Masyarakat Universitas Indonesia; 2007.

Mauger JF, Lichtenstein AH, Ausman LM, Jalbert SM, Jauhiainen M, Ehnholm C, et al. Effect of different forms of dietary hydrogenated fats on LDL particle size. Am J Clin Nutr 2003;78:370-5.

Baer DJ. What do we really know about the health effects of natural sources of trans fatty acids? Am J Clin Nutr 2012;95:267-8.

US Departement of Health and Human Services, Food and Drug Administration. Guidance for industry: trans fatty acids in nutrition labeling, nutrient content claims, health claims; small entity compliance guide. College Park: Center for Food Safety and Applied Nutrition;2003.

Lemieux I, Lamarche B, Couillard C, Pascot A, Cantin B, Dagenais GR, et al. Total cholesterol/ HDL cholesterol ratio vs LDL cholesterol/ HDL cholesterol ratio as indices of ischemic heart

disease risk in men. Arch Intern Med 2001;161: 2685-92.

Roos R. Atherosclerosis – an inflamatory disease. NEJM 2005;340:115-26.

Motard-Bélanger A, Charest A, Grenier G, Paquin P, Chouinard Y, Lemieux S, et al. Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease1,2,3. Am J Clin Nutr 2008;87:593-99.

Downar DZ, Kosmider A, Naruszewicz M. Trans fatty acids induce apoptosis in human endothelial cells. J Physiol Pharmacol 2005;56:611-25.

Chatgilialoglu C, Ferreri C, Lykakis IN, Wardman P. Tran-fatty acids dan radical stress: what are the real culprits? J BMC 2006;5:52.

McCord JM. Oxidative stress and aging: advances in basic science, diagnostics and intervention. Cutler RG, Rodriguez H. Singapore: World Scientific 2003: II: p.883-5.

Szmitko PE, Wang CH, Weisel RD, de Almeida JR, Anderson TJ, Verma S. New markers of inflamation and endothelial cell activation: part I. Circulation 2003;108:1917-23.

Hole PS, Darley RL, Alex Tonks A. Do reactive oxygen species play a role in myeloid leukemias? Blood 2011;117:5816-26.

Brown GC, Borutaite V. Nitric oxide, mitochondria, and cell death. IUBMB Life 2001; 52:189-95.

Dorfman SE, Laurent D, Gounarides JS, Li Xue, Mullarkey TL, Rocheford EC. Metabolic Implication of Dietary Trans- fatty Acids. Obesity J Org 2009;17:1200-7.

Borutaite V, Brown G. What else has to happen for nitric oxide to induce cell death. Biochem Soc Trans 2005;33:1394-5.

WHO World Health Organization Regional Office for the Western Pasific. Research guidelines for evaluating the safety, and efficacy of herbal medicines. 1993; Available at: http://apps.who. int/medicinedocs/en/d/Jh2946e/. Accessed at:

June 12, 2012.

William JR. Medical Ethics Manual. Ethics unit of The World Medical Association, 2005.

Matveyenk AV, Velduis JD, Buttler PC. Mechanisms of IGT and IFG Induce by 50% pancreatectomy Diabetes 2006;5:234-56.

Suarsana, I Nyoman. Perubahan histopatologi jaringan pankreas tikus diabetes dengan pemberian ekstrak metanol tempe. Repository IPB pada aktivitas hipoglikemik dan antioksidatif ekstrak metanol tempe pada tikus diabetes.

; Available at: http://repository.ipb.

handle/123456789/54971. Accessed at: August 11, 2012.

Bal-Price A, Brown GC. Nitric-oxide-induced

necrosis and apoptosis in PC12 cells mediated by mitochondria. Neurochem. 2000;75:1455-64.

Kuhnt K, Wagner A, Kraft J, Basu S, Jahreis G. Dietary supplementation with 11trans- and 12trans-18:1 and oxidative stress in humans1,2,3. Am J Clin Nutr 2006;84:981-8.

Mukhopadhyay P, Rajes M, Batkai S, Kashiwaya Y, Haskó G, Liaudet L, et al. Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro. Am J Physiol Heart Circ Physiol 2009;296:H1466-

Rao AM. Lipid alterations in transient forebrain ischemia: possible new mechanisms of CDP choline neuroprotection. J Neurochem 2000;75: 2528-35.

Malhi H, Gores GJ. Molecular mechanism of lipotoxicity in fatty liver disease. Semin Liver Dis 2008;28:360-9.

Stumfold M, Goldstein BJ, van haeten TW. Pathogenesis of type 2 DM. In: Goldstein BJ, Weiland. DM type 2 diabetes principles and practice. Human Press 2008;13-27.