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Oxidative stress markers in liver in streptozocin-induced diabetic rats: effects of metformin and sitagliptin

Year 2020, Volume: 45 Issue: 4, 1733 - 1741, 27.12.2020
https://doi.org/10.17826/cumj.791369

Abstract

Purpose: This study aims at investigating the oxidative stress effect of antidiabetic drugs of Metformin (MET) and sitagliptin (STG) in the liver tissue of diabetic rats from streptozotocin (STZ).
Materials and Methods: Thirty-five female Wistar rats (3-4 months old, weighing 200±25 g) were divided into five groups (with seven rats each) and treated as follows: control (Cont), streptozotocin alone (STZ), streptozotocin + metformin (STZ+MET), streptozotocin + sitagliptin (STZ+STG), streptozotocin + metformin + sitagliptin (STZ+MET+STG). Sitagliptin, Metformin, and combined metformin sitagliptin treated subgroups for four weeks. Malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS) levels, and oxidative stress index (OSI) ratio were measured in rat liver tissue. Besides, cells undergoing apoptotic cell death were determined using the TUNEL technique through histopathological evaluation.
Results: MDA, TAS, and OSI of STZ+MET+STG administered group decreased compared to STZ. TOS of STZ+MET+STG administered group decreased compared to STZ.
Conclusion: In the experimental T2D model in rats, it shows protective effect when sitagliptin is used with metformin against oxidative damage in liver tissue caused by STZ.

References

  • Mohamed J, Nazratun Nafizah AH, Zariyantey AH, Budin SB. Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation. Sultan Qaboos Univ Med J. 2016;16(2):e132-e141.
  • Shawky LM, Morsi AA, El Bana E, Hanafy SM. The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin. Biology (Basel). 2019;9(1):6.
  • Alam MM, Ahmad I, Naseem I. Inhibitory effect of quercetin in the formation of advance glycation end products of human serum albumin: An in vitro and molecular interaction study. International Journal of Biological Macromolecules. 2015;79:336-343.
  • Eitah HE, Maklad YA, Abdelkader NF, Gamal El Din AA, Badawi MA, Kenawy SA. Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats. Toxicology and applied pharmacology. 2019;365:30-40.
  • Baig NA, Herrine SK, Rubin R. Liver disease and diabetes mellitus. Clinics in laboratory medicine. 2001;21(1):193-207.
  • Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress—A concise review. Saudi Pharmaceutical Journal. 2016;24(5):547-553.
  • Bansal AK, Bilaspuri GS. Impacts of oxidative stress and antioxidants on semen functions. Veterinary medicine international. 2010;2010.
  • Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012;5(1):9-19.
  • Hostalek U, Gwilt M, Hildemann S. Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention. Drugs. 2015;75(10):1071-1094.
  • Algire C, Moiseeva O, Deschênes-Simard X, et al. Metformin Reduces Endogenous Reactive Oxygen Species and Associated DNA Damage. Cancer prevention research (Philadelphia, Pa.). 2012;5:536-543.
  • Carvalho C, Correia S, Santos M, Seiça R, Oliveira C, Moreira P. Metformin promotes isolated rat liver mitochondria impairment. Molecular and cellular biochemistry. 2008;308:75-83.
  • 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-1β (IL-1β) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages. The Journal of biological chemistry. 2015;290(33):20348-20359.
  • Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. The Biochemical journal. 2000;348 Pt 3(Pt 3):607-614.
  • Chen YT, Tsai TH, Yang CC, et al. Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. Journal of translational medicine. 2013;11:270.
  • Kumar A, Pathak R, Palfrey HA, Stone KP, Gettys TW, Murthy SN. High levels of dietary methionine improves sitagliptin-induced hepatotoxicity by attenuating oxidative stress in hypercholesterolemic rats. Nutrition & Metabolism. 2020;17(1):2.
  • Trocha M, Krzystek-Korpacka M, Merwid-Ląd A, et al. Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion. Oxidative Medicine and Cellular Longevity. 2019;2019:2738605.
  • Vaghasiya J, Sheth N, Bhalodia Y, Manek R. Sitagliptin protects renal ischemia reperfusion induced renal damage in diabetes. Regulatory peptides. 2011;166(1-3):48-54.
  • Wu KK, Huan Y. Streptozotocin-induced diabetic models in mice and rats. Current protocols in pharmacology. 2008;Chapter 5:Unit 5.47.
  • Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-1111.
  • Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical biochemistry. 2004;37(4):277-285.
  • Harma M, Harma M, Erel O. Increased oxidative stress in patients with hydatidiform mole. Swiss medical weekly. 2003;133(41-42):563-566.
  • Kosecik M, Erel O, Sevinc E, Selek Ş. Increased oxidative stress in children exposed to passive smoking. International journal of cardiology. 2005;100:61-64.
  • Yumru M, Savas HA, Kalenderoglu A, Bulut M, Celik H, Erel O. Oxidative imbalance in bipolar disorder subtypes: a comparative study. Progress in neuro-psychopharmacology & biological psychiatry. 2009;33(6):1070-1074.
  • Al-kuraishy H. Oxidative Stress Injury and Glucolipotoxicity in Type 2 Diabetes Mellitus: The Potential Role of Metformin and Sitagliptin. Biomedical and Biotechnology Research Journal. 2020;4.
  • Derosa G, D'Angelo A, Maffioli P. Sitagliptin in type 2 diabetes mellitus: Efficacy after five years of therapy. Pharmacological research. 2015;100:127-134.
  • Yabe D, Kuwata H, Kaneko M, et al. Use of the Japanese health insurance claims database to assess the risk of acute pancreatitis in patients with diabetes: comparison of DPP-4 inhibitors with other oral antidiabetic drugs. Diabetes, Obesity and Metabolism. 2015;17(4):430-434.
  • Arora R, Vig A, Arora S. Lipid Peroxidation: A Possible Marker for Diabetes. Journal of Diabetes & Metabolism. 2013;SII:007.
  • Elsawy M, Emara E. The impact of ghrelin on oxidative stress and inflammatory markers on the liver of diabetic rats. Tanta Medical Journal. 2016;44:163.
  • Emara E, Elsawy M, Elmashad W, Eldamarawi M. Effect of Vitamins (C and E) on Endothelial Inflammation Biomarkers and Oxidative Stress in Diabetic Rats. 2009.
  • Gezginci-Oktayoglu S, Basaraner H, Yanardag R. The Effects of Combined Treatment of Antioxidants on the Liver Injury in STZ Diabetic Rats. Digestive diseases and sciences. 2008;54:538-546.
  • Koyuturk M, Sacan O, Karabulut S, et al. The role of ghrelin on apoptosis, cell proliferation and oxidant-antioxidant system in the liver of neonatal diabetic rats. Cell biology international. 2015;39(7):834-841.
  • Parveen K, Khan MR, Mujeeb M, Siddiqui WA. Protective effects of Pycnogenol on hyperglycemia-induced oxidative damage in the liver of type 2 diabetic rats. Chemico-biological interactions. 2010;186(2):219-227.
  • Dogan I, Çandar T, Yuksel E, Kalay S, Oğuz AK, Demirtas S. Potential Effects of Metformin in DNA BER System Based On Oxidative Status in Type 2 Diabetes. Biochimie. 2018;154.
  • Pujadas G, De Nigris V, Prattichizzo F, La Sala L, Testa R, Ceriello A. The dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin functions as antioxidant on human endothelial cells exposed to chronic hyperglycemia and metabolic high-glucose memory. Endocrine. 2017;56(3):509-520.
  • Mistry GC, Bergman AJ, Zheng W, et al. Sitagliptin, an dipeptidyl peptidase-4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects. British journal of clinical pharmacology. 2008;66(1):36-42.
  • Ferreira L, Teixeira-de-Lemos E, Pinto F, et al. Effects of sitagliptin treatment on dysmetabolism, inflammation, and oxidative stress in an animal model of type 2 diabetes (ZDF rat). Mediators of inflammation. 2010;2010:592760.
  • Monami M, Iacomelli I, Marchionni N, Mannucci E. Dipeptydil peptidase-4 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2010;20(4):224-235.
  • Hamden K, Carreau S, Boujbiha MA, et al. Hyperglycaemia, stress oxidant, liver dysfunction and histological changes in diabetic male rat pancreas and liver: protective effect of 17 beta-estradiol. Steroids. 2008;73(5):495-501.
  • Seven A, Guzel S, Seymen O, et al. Effects of vitamin E supplementation on oxidative stress in streptozotocin induced diabetic rats: investigation of liver and plasma. Yonsei medical journal. 2004;45(4):703-710.
  • Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury. Journal of gastroenterology and hepatology. 2000;15(7):718-724.
  • Zhang C, Lu X, Tan Y, et al. Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model. PloS one. 2012;7(12):e49257.
  • Noor A, Gunasekaran S, Amirtham S, Vijayalakshmi MA. Antidiabetic activity of Aloe vera and histology of organs in streptozotocin-induced diabetic rats. Current Science. 2008;94:1070-1076.
  • Kume E, Fujimura H, Matsuki N, et al. Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice. Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie. 2004;55(6):467-480.
  • Brůha R, Dvořák K, Petrtýl J. [Liver disorders in diabetic patients]. Vnitrni lekarstvi. 2013;59(7):546-550.
  • Aksoy N, Vural H, Sabuncu T, Aksoy S. Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats. Cell biochemistry and function. 2003;21(2):121-125.
  • Baydas G, Reiter R, Yasar A, Tuzcu M, Akdemir I, Nedzvetsky V. Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats. Free radical biology & medicine. 2003;35:797-804.
  • Winiarska K, Fraczyk T, Malinska D, Drozak J, Bryla J. Melatonin attenuates diabetes-induced oxidative stress in rabbits. Journal of pineal research. 2006;40(2):168-176.

Streptozotosin kaynaklı diyabetik sıçanların karaciğerindeki oksidatif stres belirteçleri: metformin ve sitagliptinin etkileri

Year 2020, Volume: 45 Issue: 4, 1733 - 1741, 27.12.2020
https://doi.org/10.17826/cumj.791369

Abstract

Amaç: Bu çalışmanın amacı, streptozotosin (STZ) kaynaklı diyabetik sıçanların karaciğer dokusunda metformin (MET) ve/veya sitagliptinin (STG) antidiyabetik ilaçların olası oksidatif stres etkisini araştırmaktır.
Gereç ve Yöntem: Bu çalışmada erişkin dişi Wistar albino sıçanları kullanılmış ve rastgele kontrol normal grubu, kontrol diyabetik grubu ve diyabetik gruba ayrılmıştır. Antidiyabetik ilaç grubuna sahip diyabetik sıçanlar aşağıdaki tedavi edilen alt gruplara ayrıldı: Sitagliptin (10 mg/ kg/ gün), Metformin (200mg/ kg/ gün) ve Kombine metformin sitagliptin ile 4 hafta boyunca tedavi edilen alt gruplar. Sıçan karaciğer dokusunda oksidatif stres belirteçleri (Malondialdehid (MDA), total antioksidan durum (TAS), total oksidan durum (TOS) ve oksidatif stres indeksi (OSI) seviyeleri) ölçüldü. Ek olarak, apoptotik hücre ölümü geçiren hücreler histopatolojik değerlendirme ile TUNEL tekniği kullanılarak belirlendi.
Bulgular: STZ + MET + STG uygulanan grubun MDA, TAS ve OSI'si STZ'ye göre azaldı. STZ + MET + STG uygulanan grubun TOS'u STZ'ye göre azaldı.
Sonuç: Sıçanlarda deneysel T2D modelinde, sitagliptin metformin ile birlikte kullanıldığında karaciğer dokusunda STZ'nin neden olduğu oksidatif hasara karşı koruyucu etki göstermektedir.

References

  • Mohamed J, Nazratun Nafizah AH, Zariyantey AH, Budin SB. Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation. Sultan Qaboos Univ Med J. 2016;16(2):e132-e141.
  • Shawky LM, Morsi AA, El Bana E, Hanafy SM. The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin. Biology (Basel). 2019;9(1):6.
  • Alam MM, Ahmad I, Naseem I. Inhibitory effect of quercetin in the formation of advance glycation end products of human serum albumin: An in vitro and molecular interaction study. International Journal of Biological Macromolecules. 2015;79:336-343.
  • Eitah HE, Maklad YA, Abdelkader NF, Gamal El Din AA, Badawi MA, Kenawy SA. Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats. Toxicology and applied pharmacology. 2019;365:30-40.
  • Baig NA, Herrine SK, Rubin R. Liver disease and diabetes mellitus. Clinics in laboratory medicine. 2001;21(1):193-207.
  • Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress—A concise review. Saudi Pharmaceutical Journal. 2016;24(5):547-553.
  • Bansal AK, Bilaspuri GS. Impacts of oxidative stress and antioxidants on semen functions. Veterinary medicine international. 2010;2010.
  • Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012;5(1):9-19.
  • Hostalek U, Gwilt M, Hildemann S. Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention. Drugs. 2015;75(10):1071-1094.
  • Algire C, Moiseeva O, Deschênes-Simard X, et al. Metformin Reduces Endogenous Reactive Oxygen Species and Associated DNA Damage. Cancer prevention research (Philadelphia, Pa.). 2012;5:536-543.
  • Carvalho C, Correia S, Santos M, Seiça R, Oliveira C, Moreira P. Metformin promotes isolated rat liver mitochondria impairment. Molecular and cellular biochemistry. 2008;308:75-83.
  • 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-1β (IL-1β) and Boosts Interleukin-10 (IL-10) in Lipopolysaccharide (LPS)-activated Macrophages. The Journal of biological chemistry. 2015;290(33):20348-20359.
  • Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. The Biochemical journal. 2000;348 Pt 3(Pt 3):607-614.
  • Chen YT, Tsai TH, Yang CC, et al. Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. Journal of translational medicine. 2013;11:270.
  • Kumar A, Pathak R, Palfrey HA, Stone KP, Gettys TW, Murthy SN. High levels of dietary methionine improves sitagliptin-induced hepatotoxicity by attenuating oxidative stress in hypercholesterolemic rats. Nutrition & Metabolism. 2020;17(1):2.
  • Trocha M, Krzystek-Korpacka M, Merwid-Ląd A, et al. Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion. Oxidative Medicine and Cellular Longevity. 2019;2019:2738605.
  • Vaghasiya J, Sheth N, Bhalodia Y, Manek R. Sitagliptin protects renal ischemia reperfusion induced renal damage in diabetes. Regulatory peptides. 2011;166(1-3):48-54.
  • Wu KK, Huan Y. Streptozotocin-induced diabetic models in mice and rats. Current protocols in pharmacology. 2008;Chapter 5:Unit 5.47.
  • Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-1111.
  • Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical biochemistry. 2004;37(4):277-285.
  • Harma M, Harma M, Erel O. Increased oxidative stress in patients with hydatidiform mole. Swiss medical weekly. 2003;133(41-42):563-566.
  • Kosecik M, Erel O, Sevinc E, Selek Ş. Increased oxidative stress in children exposed to passive smoking. International journal of cardiology. 2005;100:61-64.
  • Yumru M, Savas HA, Kalenderoglu A, Bulut M, Celik H, Erel O. Oxidative imbalance in bipolar disorder subtypes: a comparative study. Progress in neuro-psychopharmacology & biological psychiatry. 2009;33(6):1070-1074.
  • Al-kuraishy H. Oxidative Stress Injury and Glucolipotoxicity in Type 2 Diabetes Mellitus: The Potential Role of Metformin and Sitagliptin. Biomedical and Biotechnology Research Journal. 2020;4.
  • Derosa G, D'Angelo A, Maffioli P. Sitagliptin in type 2 diabetes mellitus: Efficacy after five years of therapy. Pharmacological research. 2015;100:127-134.
  • Yabe D, Kuwata H, Kaneko M, et al. Use of the Japanese health insurance claims database to assess the risk of acute pancreatitis in patients with diabetes: comparison of DPP-4 inhibitors with other oral antidiabetic drugs. Diabetes, Obesity and Metabolism. 2015;17(4):430-434.
  • Arora R, Vig A, Arora S. Lipid Peroxidation: A Possible Marker for Diabetes. Journal of Diabetes & Metabolism. 2013;SII:007.
  • Elsawy M, Emara E. The impact of ghrelin on oxidative stress and inflammatory markers on the liver of diabetic rats. Tanta Medical Journal. 2016;44:163.
  • Emara E, Elsawy M, Elmashad W, Eldamarawi M. Effect of Vitamins (C and E) on Endothelial Inflammation Biomarkers and Oxidative Stress in Diabetic Rats. 2009.
  • Gezginci-Oktayoglu S, Basaraner H, Yanardag R. The Effects of Combined Treatment of Antioxidants on the Liver Injury in STZ Diabetic Rats. Digestive diseases and sciences. 2008;54:538-546.
  • Koyuturk M, Sacan O, Karabulut S, et al. The role of ghrelin on apoptosis, cell proliferation and oxidant-antioxidant system in the liver of neonatal diabetic rats. Cell biology international. 2015;39(7):834-841.
  • Parveen K, Khan MR, Mujeeb M, Siddiqui WA. Protective effects of Pycnogenol on hyperglycemia-induced oxidative damage in the liver of type 2 diabetic rats. Chemico-biological interactions. 2010;186(2):219-227.
  • Dogan I, Çandar T, Yuksel E, Kalay S, Oğuz AK, Demirtas S. Potential Effects of Metformin in DNA BER System Based On Oxidative Status in Type 2 Diabetes. Biochimie. 2018;154.
  • Pujadas G, De Nigris V, Prattichizzo F, La Sala L, Testa R, Ceriello A. The dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin functions as antioxidant on human endothelial cells exposed to chronic hyperglycemia and metabolic high-glucose memory. Endocrine. 2017;56(3):509-520.
  • Mistry GC, Bergman AJ, Zheng W, et al. Sitagliptin, an dipeptidyl peptidase-4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects. British journal of clinical pharmacology. 2008;66(1):36-42.
  • Ferreira L, Teixeira-de-Lemos E, Pinto F, et al. Effects of sitagliptin treatment on dysmetabolism, inflammation, and oxidative stress in an animal model of type 2 diabetes (ZDF rat). Mediators of inflammation. 2010;2010:592760.
  • Monami M, Iacomelli I, Marchionni N, Mannucci E. Dipeptydil peptidase-4 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2010;20(4):224-235.
  • Hamden K, Carreau S, Boujbiha MA, et al. Hyperglycaemia, stress oxidant, liver dysfunction and histological changes in diabetic male rat pancreas and liver: protective effect of 17 beta-estradiol. Steroids. 2008;73(5):495-501.
  • Seven A, Guzel S, Seymen O, et al. Effects of vitamin E supplementation on oxidative stress in streptozotocin induced diabetic rats: investigation of liver and plasma. Yonsei medical journal. 2004;45(4):703-710.
  • Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury. Journal of gastroenterology and hepatology. 2000;15(7):718-724.
  • Zhang C, Lu X, Tan Y, et al. Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model. PloS one. 2012;7(12):e49257.
  • Noor A, Gunasekaran S, Amirtham S, Vijayalakshmi MA. Antidiabetic activity of Aloe vera and histology of organs in streptozotocin-induced diabetic rats. Current Science. 2008;94:1070-1076.
  • Kume E, Fujimura H, Matsuki N, et al. Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice. Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie. 2004;55(6):467-480.
  • Brůha R, Dvořák K, Petrtýl J. [Liver disorders in diabetic patients]. Vnitrni lekarstvi. 2013;59(7):546-550.
  • Aksoy N, Vural H, Sabuncu T, Aksoy S. Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats. Cell biochemistry and function. 2003;21(2):121-125.
  • Baydas G, Reiter R, Yasar A, Tuzcu M, Akdemir I, Nedzvetsky V. Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats. Free radical biology & medicine. 2003;35:797-804.
  • Winiarska K, Fraczyk T, Malinska D, Drozak J, Bryla J. Melatonin attenuates diabetes-induced oxidative stress in rabbits. Journal of pineal research. 2006;40(2):168-176.
There are 47 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

Suat Çakına 0000-0002-3990-7641

Şamil Öztürk 0000-0002-9435-8139

Publication Date December 27, 2020
Acceptance Date October 1, 2020
Published in Issue Year 2020 Volume: 45 Issue: 4

Cite

MLA Çakına, Suat and Şamil Öztürk. “Oxidative Stress Markers in Liver in Streptozocin-Induced Diabetic Rats: Effects of Metformin and Sitagliptin”. Cukurova Medical Journal, vol. 45, no. 4, 2020, pp. 1733-41, doi:10.17826/cumj.791369.