Yıl: 2022 Cilt: 26 Sayı: 3 Sayfa Aralığı: 543 - 553 Metin Dili: İngilizce DOI: 10.29228/jrp.151 İndeks Tarihi: 08-06-2022

The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice

Öz:
Due to prolonged hyperglycemia many of the diabetic patients suffer from complications such as liver damage. Diabetic patients are known to have the need for liver surgeries more than non-diabetic do. The ischemia reperfusion injuries (IRI) are one of the main complications of these surgeries and the IRI-related increase in oxidative stress has been known to be higher in diabetic patients. Metformin and aerobic exercise are important tools being used especially in type-2 diabetes. However, their effects and roles in liver IRI in type-1 diabetic patients are not known. This study aimed to investigate the effects of metformin and exercise on hepatic IRI in diabetes in streptozotocin induced type-1 diabetic mice. Diabetes was induced by streptozotocin and two weeks after the disease developed, mice were started to treat with metformin and/or aerobic exercise during four-weeks. Blood glucose levels of the mice were measured again and the glucose tolerance test (OGTT) was performed for each mouse. The day after OGTT, ischemia was performed for 45 minutes in the liver and then reperfusion was provided for 5 hours. The liver of the mice was isolated at the end of the experiments. The malondialdehyde, superoxide dismutase and nitrite levels were measured with colorimetric analysis. Metformin reduced the insulin resistance alone and together with aerobic exercise. Oxidative stress in the liver after IRI was diminished both with metformin and/or aerobic exercise in diabetic mice. Our study indicated that metformin accompanied with aerobic exercise might be an important treatment strategy for preventing the IRI in the liver of type-1 diabetic patients.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • [1] Lejay A, Fang F, John R, Van JA, Barr M, Thaveau F, Chakfe N, Geny B, Scholey JW. Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus. J Mol Cell Cardiol. 2016; 91: 11-22 [CrossRef]
  • [2] Yue S, Zhou HM, Zhu JJ, Rao JH, Busuttil RW, Kupiec-Weglinski JW, Lu L, Zhai Y. Hyperglycemia and liver ischemia reperfusion injury: a role for the advanced glycation endproduct and its receptor pathway. Am J Transplant. 2015; 15(11) :2877-2887 [CrossRef].
  • [3] de Lemos ET, Oliveira J, Pinheiro JP, Reis F. Regular physical exercise as a strategy to improve antioxidant and antiinflammatory status: benefits in type 2 diabetes mellitus. Oxid Med Cell Longev. 2012; 2012:741545 [CrossRef].
  • [4] Ranjbar K, Nazem F, Sabrinezhad R, Nazari A. Aerobic training and L-arginine supplement attenuates myocardial infarction-induced kidney and liver injury in rats via reduced oxidative stress. Indian Heart J. 2019; 71(6): 496-496 [CrossRef].
  • [5] Zhang HJ, Ren JH, Yazdani HO, Van der Windt D, Zhang JX, Tsung A, Huang H. Preoperative exercise therapy protects the liver from ischemia-reperfusion injury. Journal of Immunology. 2018; 200 (1 Supplement): 49.17.
  • [6] Beysel S, Unsal IO, Kizilgul M, Caliskan M, Ucan B, Cakal E. The effects of metformin in type 1 diabetes mellitus. BMC Endocr Disord. 2018; 18(1): 1 [CrossRef].
  • [7] Snaith JR, Samocha-Bonet D, Evans J, Liu Z, Kowalski G, Bruce C, Holmes-Walker DJ, Greenfield JR. Insulin resistance in type 1 diabetes managed with metformin (INTIMET): Study protocol of a double-blind placebo-controlled, randomised trial. Diabet Med. 2021; 38(9): e14564 [CrossRef].
  • [8] Teupe B, Bergis K. Epidemiological evidence for "double diabetes". Lancet. 1991; 337(8737): 361-362 [CrossRef].
  • [9] Merger SR, Kerner W, Stadler M, Zeyfang A, Jehle P, Muller-Korbsch M, Holl RW, Initiative DPV, German BCNDm. Prevalence and comorbidities of double diabetes. Diabetes Res Clin Pract. 2016; 119: 48-56 [CrossRef].
  • [10] Libman IM, Miller KM, DiMeglio LA, Bethin KE, Katz ML, Shah A, Simmons JH, Haller MJ, Raman S, Tamborlane WV, Coffey JK, Saenz AM, Beck RW, Nadeau KJ, Group TDECNMRS. Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2015; 314(21): 2241-2250 [CrossRef].
  • [11] Setoodeh A, Didban A, Rabbani A, Sayarifard A, Abbasi F, Sayarifard F, Hoseinzade F. The Effect of Metformin as an Adjunct Therapy in Adolescents with Type 1 Diabetes. J Clin Diagn Res. 2017; 11(4):SC01-SC04 [CrossRef].
  • [12] Esteghamati A, Eskandari D, Mirmiranpour H, Noshad S, Mousavizadeh M, Hedayati M, Nakhjavani M. Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: a randomized clinical trial. Clin Nutr. 2013; 32(2):179-185 [CrossRef].
  • [13] Kelly B, Tannahill GM, Murphy MP, O'Neill LA. Metformin Inhibits the Production of Reactive Oxygen Species from NADH:Ubiquinone Oxidoreductase to Limit Induction of Interleukin-1beta (IL-1beta) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages. J Biol Chem. 2015; 290(33):20348-20359 [CrossRef].
  • [14] Jiang A, Du P, Liu Y, Pu J, Shi J, Zhang H. Metformin regulates the Th17/Treg balance by glycolysis with TIGAR in hepatic ischemia-reperfusion injury. J Pharmacol Sci. 2021; 146(1):40-48 [CrossRef].
  • [15] Li X, Wang L, Yang X, Huang C. Metformin Attenuates Ischemia-reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4/NF-kappaB Axis. Balkan Med J. 2020; 37(4):196-202 [CrossRef].
  • [16] Priya G, Kalra S. A Review of Insulin Resistance in Type 1 Diabetes: Is There a Place for Adjunctive Metformin? Diabetes Ther. 2018; 9(1):349-361 [CrossRef]
  • [17] Livingstone R, Boyle JG, Petrie JR, Team RS. A new perspective on metformin therapy in type 1 diabetes. Diabetologia. 2017; 60(9):1594-1600 [CrossRef].
  • [18] Munir KM, Davis SN. The treatment of type 1 diabetes mellitus with agents approved for type 2 diabetes mellitus. Expert Opin Pharmacother. 2015; 16(15):2331-2341 [CrossRef].
  • [19] American Diabetes Association. Understanding Insulin Resistance. https://www.diabetes.org/healthyliving/ medication-treatments/insulin-resistance (accessed January 10, 2022).
  • [20] Zanuso S, Jimenez A, Pugliese G, Corigliano G, Balducci S. Exercise for the management of type 2 diabetes: a review of the evidence. Acta Diabetol. 2010; 47(1): 15-22 [CrossRef]
  • [21] Golbidi S, Ebadi SA, Laher I. Antioxidants in the treatment of diabetes. Curr Diabetes Rev. 2011; 7(2): 106-125 [CrossRef].
  • [22] Colberg SR, Bevier WC, Pinsker JE, Lee JB, Ehrlich B, Dassau E, Doyle FJ, 3rd, Chen KY, Kerr D. Challenges Associated With Exercise Studies in Type 1 Diabetes. J Diabetes Sci Technol. 2016; 10(4): 993-994 [CrossRef].
  • [23] Tonoli C, Heyman E, Roelands B, Buyse L, Cheung SS, Berthoin S, Meeusen R. Effects of different types of acute and chronic (training) exercise on glycaemic control in type 1 diabetes mellitus: a meta-analysis. Sports Med. 2012; 42(12): 1059- 1080 [CrossRef].
  • [24] Zhang YH, Yuan DD, Yao WF, Zhu QQ, Liu Y, Huang F, Feng JY, Chen X, Huang Y, Chi XJ, Hei ZQ. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation. Oxidative Medicine and Cellular Longevity. 2016; 2016 [CrossRef].
  • [25] Kim WR, Smith JM, Skeans MA, Schladt DP, Schnitzler MA, Edwards EB, Harper AM, Wainright JL, Snyder JJ, Israni AK, Kasiske BL. OPTN/SRTR 2012 Annual Data Report: liver. Am J Transplant. 2014; 14 Suppl 1:69-96 [CrossRef].
  • [26] Francescato MP, Stel G, Geat M, Cauci S. Oxidative stress in patients with type 1 diabetes mellitus: is it affected by a single bout of prolonged exercise? PLoS One. 2014; 9(6):e99062 [CrossRef].
  • [27] Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010; 107(9): 1058-1070 [CrossRef].
  • [28] Kowluru RA, Kowluru V, Xiong Y, Ho YS. Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress. Free Radic Biol Med. 2006; 41(8): 1191-1196 [CrossRef].
  • [39] Kim JS, Lee YH, Kim JC, Ko YH, Yoon CS, Yi HK. Effect of exercise training of different intensities on antiinflammatory reaction in streptozotocin-induced diabetic rats. Biol Sport. 2014; 31(1): 73-79 [CrossRef].
  • [30] Yanardag R, Ozsoy-Sacan O, Bolkent S, Orak H, Karabulut-Bulan O. Protective effects of metformin treatment on the liver injury of streptozotocin-diabetic rats. Hum Exp Toxicol. 2005; 24(3): 129-135 [CrossRef].
  • [31] Turk J, Corbett JA, Ramanadham S, Bohrer A, McDaniel ML. Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochem Biophys Res Commun. 1993; 197(3): 1458-1464 [CrossRef].
  • [32] Gvazava IG, Rogovaya OS, Borisov MA, Vorotelyak EA, Vasiliev AV. Pathogenesis of Type 1 Diabetes Mellitus and Rodent Experimental Models. Acta Naturae. 2018; 10(1): 24-33.
  • [33] Campos-Rodriguez R, Godinez-Victoria M, Arciniega-Martinez IM, Resendiz-Albor AA, Reyna-Garfias H, Cruz- Hernandez TR, Drago-Serrano ME. Protective Effect of Moderate Exercise for BALB/c Mice with Salmonella Typhimurium Infection. Int J Sports Med. 2016; 37(1): 63-70 [CrossRef].
  • [34] Liu G, Chen L, Cai Q, Wu H, Chen Z, Zhang X, Lu P. Streptozotocininduced diabetic mice exhibit reduced experimental choroidal neovascularization but not corneal neovascularization. Mol Med Rep. 2018; 18(5): 4388-4398 [CrossRef].
  • [35] Furman BL. Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr Protoc Pharmacol. 2015; 70: 5.47.1-5.47.20 [CrossRef].
  • [36] Nogueira PAS, Pereira MP, Soares JJG, Filho AFN, Tanimoto IMF, Fonseca IAT, Avelar HO, Botelho FV, Roever L, Vieira AA, Zanon RG. Physiological adaptations induced by swimming in mice fed a high fat diet. J Exerc Rehabil. 2017; 13(3): 284-291 [CrossRef].
  • [37] Sadeghi H, Jahanbazi F, Sadeghi H, Omidifar N, Alipoor B, Kokhdan EP, Mousavipoor SM, Mousavi-Fard SH, Doustimotlagh AH. Metformin attenuates oxidative stress and liver damage after bile duct ligation in rats. Res Pharm Sci. 2019; 14(2): 122-129 [CrossRef].
  • [38] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2): 351-358 [CrossRef].
  • [39] Peskin AV, Winterbourn CC. A microtiter plate assay for superoxide dismutase using a water-soluble tetrazolium salt (WST-1). Clin Chim Acta. 2000; 293(1-2): 157-166 [CrossRef].
  • [40] Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001; 5(1): 62-71 [CrossRef]
APA TELLI G, TELLİ-ATALAY O (2022). The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. , 543 - 553. 10.29228/jrp.151
Chicago TELLI GOKÇEN,TELLİ-ATALAY Orçin The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. (2022): 543 - 553. 10.29228/jrp.151
MLA TELLI GOKÇEN,TELLİ-ATALAY Orçin The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. , 2022, ss.543 - 553. 10.29228/jrp.151
AMA TELLI G,TELLİ-ATALAY O The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. . 2022; 543 - 553. 10.29228/jrp.151
Vancouver TELLI G,TELLİ-ATALAY O The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. . 2022; 543 - 553. 10.29228/jrp.151
IEEE TELLI G,TELLİ-ATALAY O "The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice." , ss.543 - 553, 2022. 10.29228/jrp.151
ISNAD TELLI, GOKÇEN - TELLİ-ATALAY, Orçin. "The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice". (2022), 543-553. https://doi.org/10.29228/jrp.151
APA TELLI G, TELLİ-ATALAY O (2022). The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. Journal of research in pharmacy (online), 26(3), 543 - 553. 10.29228/jrp.151
Chicago TELLI GOKÇEN,TELLİ-ATALAY Orçin The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. Journal of research in pharmacy (online) 26, no.3 (2022): 543 - 553. 10.29228/jrp.151
MLA TELLI GOKÇEN,TELLİ-ATALAY Orçin The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. Journal of research in pharmacy (online), vol.26, no.3, 2022, ss.543 - 553. 10.29228/jrp.151
AMA TELLI G,TELLİ-ATALAY O The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. Journal of research in pharmacy (online). 2022; 26(3): 543 - 553. 10.29228/jrp.151
Vancouver TELLI G,TELLİ-ATALAY O The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice. Journal of research in pharmacy (online). 2022; 26(3): 543 - 553. 10.29228/jrp.151
IEEE TELLI G,TELLİ-ATALAY O "The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice." Journal of research in pharmacy (online), 26, ss.543 - 553, 2022. 10.29228/jrp.151
ISNAD TELLI, GOKÇEN - TELLİ-ATALAY, Orçin. "The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin- Induced Diabetic Mice". Journal of research in pharmacy (online) 26/3 (2022), 543-553. https://doi.org/10.29228/jrp.151