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Deneysel Diyabetik Sıçanlarda Metformin, E Vitamini ve Çörek Otu Yağının Karaciğer Dokusu Üzerine Hepatoprotektif Etkilerinin Karşılaştırılması

Year 2022, Volume: 19 Issue: 2, 421 - 427, 28.08.2022
https://doi.org/10.35440/hutfd.1087068

Abstract

ÖZET
Amaç: Amacımız, diyabetik ratlarda gelişen karaciğer hasarına karşı Metformin, E vitamini ve Çörek otu yağının hepotoprotektif etkilerini karşılaştırmaktır. Materyal ve Metod: 30 adet Wistar Albino rat, Kontrol (n:6), Diyabet (n:6), Diyabet + Çörek Otu Yağı (n:6), Diyabet + E Vitamini (n:6) ve Diyabet + Metformin (n:6) olarak 5 gruba ayrıldı. Diyabeti indüklemek amacıyla tek doz 45 mg/kg Streptozotosin (STZ) intraperitoneal yolla uygulandı. Diyabet + E vitamini grubuna 100 mg/kg/gün E vitamini, Diyabet + Metformin grubuna 100 mg/kg/gün metformin ve Diyabet + Çörek otu yağı grubuna 2.5 ml/kg/gün çörek otu yağı oral yollarla uygulandı. Karaciğer dokularından elde edilen parafin kesitler Hematoksilen-Eozin, Masson Trikrom ve PAS boyaları ile boyandı. Bulgular: Diyabet grubu karaciğer kesitlerinde vakuolizasyon, piknotik çekirdek, sinüzoidlerde dilatasyon, azalan glikojen içeriği ve konjesyon izlendi. Metformin grubunda hasar bulgularında kısmen ve E vitamini grubunda ise minimal iyileşme görüldü. Çörek otu yağı grubunun bulguları ise kontrol grubuna benzerdi. Sonuç: Diyabette gelişen karaciğer hasarına karşı çörek otu yağının etkili olabileceği belirlendi.

Supporting Institution

Dicle Üniversitesi Bilimsel Araştırma Projeleri (DÜBAP) Komisyonu Başkanlığı

Project Number

TIP.20.002

References

  • 1. Carvalho DS, de Almeida AA, Borges AF, Vannucci Campos D. Treatments for diabetes mellitus type II: New perspectives regarding the possible role of calcium and cAMP interaction. European journal of pharmacology. 2018;830:9-16.
  • 2. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40-50.
  • 3. Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018;9(2):119.
  • 4. Palsamy P, Sivakumar S, Subramanian S. Resveratrol attenuates hyperglycemia-mediated oxidative stress, proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin-nicotinamide-induced experimental diabetic rats. Chem Biol Interact. 2010;186(2):200-10.
  • 5. Zou W, Zhang C, Gu X, Li X, Zhu H. Metformin in Combination with Malvidin Prevents Progression of Non-Alcoholic Fatty Liver Disease via Improving Lipid and Glucose Metabolisms, and Inhibiting Inflammation in Type 2 Diabetes Rats. Drug design, development and therapy. 2021;15:2565-76.
  • 6. Punithavathi VR, Anuthama R, Prince PS. Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats. Journal of applied toxicology : JAT. 2008;28(6):806-13.
  • 7. Khan Z, Hasan N, Ahmad N, Vartika S, Khalid M, Singh PK, Ahmad Z, Zohrameena S. Pharmacological Activity of Nigella Sativa: A Review. World Journal of Pharmaceutical Sciences. 2016;4:234-41.
  • 8. Shady AM, Nooh HZ. Effect of Black Seed (Nigella Sativa) on Compact Bone of Streptozotocin Induced Diabetic Rats. The Egyptian Journal of Histology. 2010;33:168 77.
  • 9. Kaleem M, Kirmani D, Asif M, Ahmed Q, Bano B. Biochemical effects of Nigella sativa L seeds in diabetic rats. Indian journal of experimental biology. 2006;44(9):745-8.
  • 10. Seker U, Kaya S, Kandemir S, Sener D, Demirel O, Nergiz Y. Effects of Black Cumin Seed Oil on Oxidative Stress and Expression of Membrane-Cytoskeleton Linker Proteins, Radixin and Moesin, in Streptozotocin Induced Diabetic Liver2022:21-6.
  • 11. Institute of Medicine Panel on Dietary A, Related C. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC): National Academies Press (US) Copyright 2000 by the National Academy of Sciences. All rights reserved.; 2000.
  • 12. Hacioglu C, Kar F, Kara Y, Yucel E, Donmez DB, Sentürk H, Kanbak G. Comparative effects of metformin and Cistus laurifolius L. extract in streptozotocin-induced diabetic rat model: oxidative, inflammatory, apoptotic, and histopathological analyzes. Environmental science and pollution research international. 2021;28(41):57888-901.
  • 13. Grzybowska M, Bober J, Olszewska M. [Metformin - mechanisms of action and use for the treatment of type 2 diabetes mellitus]. Postepy higieny i medycyny doswiadczalnej (Online). 2011;65:277-85.
  • 14. Behera SR, Sekkizhar M, Babu S. Nephro-protective Effect of Aqueous Extract of Syzygium cumini Seed on Streptozotocin Induced Diabetes in Rats. International Journal of Chemical and Lifesciences. 2019;3(2):1285-8.
  • 15. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Catechin Treatment Ameliorates Diabetes and Its Complications in Streptozotocin-Induced Diabetic Rats. Dose-response : a publication of International Hormesis Society. 2017;15(1):1559325817691158.
  • 16. Sahinturk V, Guclu C, Baycu C. Protective effects of vitamin E on ethane dimethane sulfonate-induced testicular toxicity in rats. Asian journal of andrology. 2007;9(1):117-24.
  • 17. Houcher Z, Boudiaf K, Benboubetra M, Houcher B. Effects of Methanolic Extract and Commercial Oil of Nigella sativa L. on Blood Glucose and Antioxidant Capacity in Alloxan-Induced Diabetic Rats. Pteridines. 2007;18(1):8-18.
  • 18. Rashid U, Khan MR. Phytochemicals of Periploca aphylla Dcne. ameliorated streptozotocin-induced diabetes in rat. Environmental health and preventive medicine. 2021;26(1):38.
  • 19. Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabetic medicine : a journal of the British Diabetic Association. 1997;14 (Suppl 5):S1-85.
  • 20. Mohamed J, Nazratun Nafizah AH, Zariyantey AH, Budin SB. Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation. Sultan Qaboos University medical journal. 2016;16(2):e132-41.
  • 21. El-Shemi AG, Kensara OA, Alsaegh A, Mukhtar MH. Pharmacotherapy with Thymoquinone Improved Pancreatic β-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats. Pharmacology. 2018;101(1-2):9-21.
  • 22. Li S, Huang Q, Zhang L, Qiao X, Zhang Y, Tang F, Li Z. Effect of CAPE-pNO2 against type 2 diabetes mellitus via the AMPK/GLUT4/ GSK3β/PPARα pathway in HFD/STZ-induced diabetic mice. European journal of pharmacology. 2019;853:1-10.
  • 23. Abdellatif NA. Protective Effect of Nigella Sativa Against Diabetic Complications on The Liver in White Male Rats. The Egyptian Journal of Hospital Medicine. 2013;53(1):1072-82.
  • 24. 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. Human & experimental toxicology. 2005;24(3):129-35.
  • 25. Gezginci-Oktayoglu S, Basaraner H, Yanardag R, Bolkent S. The effects of combined treatment of antioxidants on the liver injury in STZ diabetic rats. Digestive diseases and sciences. 2009;54(3):538-46.
  • 26. Balamash KS, Alkreathy HM, Al Gahdali EH, Khoja SO, Ahmad A. Comparative Biochemical and Histopathological Studies on the Efficacy of Metformin and Virgin Olive Oil against Streptozotocin-Induced Diabetes in Sprague-Dawley Rats. Journal of diabetes research. 2018;2018:4692197.
  • 27. Aktaş İ, Mehmet Gür F. Hepato-protective effects of thymoquinone and beta-aminoisobutyric acid in streptozocin induced diabetic rats. Biotechnic & histochemistry : official publication of the Biological Stain Commission. 2022;97(1):67-76.
  • 28. Abdellatif NA. Protective Effect of Nigella Sativa Against Diabetic Complications on The Liver in White Male Rats. The Egyptian Journal of Hospital Medicine. 2013;53:1072-82.
  • 29. Abdelrazek HMA, Kilany OE, Muhammad MAA, Tag HM, Abdelazim AM. Black Seed Thymoquinone Improved Insulin Secretion, Hepatic Glycogen Storage, and Oxidative Stress in Streptozotocin-Induced Diabetic Male Wistar Rats. Oxidative medicine and cellular longevity. 2018;2018:8104165.
  • 30. Daniel OO, Adeoye AO, Ojowu J, Olorunsogo OO. Inhibition of liver mitochondrial membrane permeability transition pore opening by quercetin and vitamin E in streptozotocin-induced diabetic rats. Biochemical and biophysical research communications. 2018;504(2):460-9.

Comparison of Hepatoprotective Effects of Metformin, Vitamin E and Black Seed Oil on Liver Tissue in Experimental Diabetic Rats

Year 2022, Volume: 19 Issue: 2, 421 - 427, 28.08.2022
https://doi.org/10.35440/hutfd.1087068

Abstract


Background: The aim of the study was to compare the hepatoprotective effects of metformin, vitamin E and black seed oil against liver damage developed in diabetic rats.
Materials and Methods: 30 Wistar Albino rats Control (n:6), Diabetes (n:6), Diabetes + Black Cumin Oil (n:6), Diabetes + Vitamin E (n:6) and Diabetes + Metformin (n:6) were divided into 5 groups. In order to induce diabetes, a single dose of 45 mg/kg Streptozotocin was administered intraperitoneally. 100 mg/kg/day vitamin E was administered to the Diabetes + Vitamin E group, 100 mg/kg/day metformin to the Diabetes + Metformin group, and 2.5 ml/kg/day black seed oil to the Diabetes + Black Cumin oil group. Paraffin sections obtained from liver tissues were stained with Hematoxylin-Eosin, Masson Trichrome and PAS stains.
Results: Vacuolization, pycnotic core, dilatation of sinusoids, decreased glycogen content and congestion were observed in liver sections of diabetes group. There was partial improvement in the damage findings in the metformin group and minimal improvement in the vitamin E group. It was seen that the black seed oil group had a better effect in the evaluation of damage scoring than other treatment applications. p<0.01.
Conclusions: It is thought that black cumin oil may have healing effects against liver damage caused by diabetes.

Project Number

TIP.20.002

References

  • 1. Carvalho DS, de Almeida AA, Borges AF, Vannucci Campos D. Treatments for diabetes mellitus type II: New perspectives regarding the possible role of calcium and cAMP interaction. European journal of pharmacology. 2018;830:9-16.
  • 2. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40-50.
  • 3. Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018;9(2):119.
  • 4. Palsamy P, Sivakumar S, Subramanian S. Resveratrol attenuates hyperglycemia-mediated oxidative stress, proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin-nicotinamide-induced experimental diabetic rats. Chem Biol Interact. 2010;186(2):200-10.
  • 5. Zou W, Zhang C, Gu X, Li X, Zhu H. Metformin in Combination with Malvidin Prevents Progression of Non-Alcoholic Fatty Liver Disease via Improving Lipid and Glucose Metabolisms, and Inhibiting Inflammation in Type 2 Diabetes Rats. Drug design, development and therapy. 2021;15:2565-76.
  • 6. Punithavathi VR, Anuthama R, Prince PS. Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats. Journal of applied toxicology : JAT. 2008;28(6):806-13.
  • 7. Khan Z, Hasan N, Ahmad N, Vartika S, Khalid M, Singh PK, Ahmad Z, Zohrameena S. Pharmacological Activity of Nigella Sativa: A Review. World Journal of Pharmaceutical Sciences. 2016;4:234-41.
  • 8. Shady AM, Nooh HZ. Effect of Black Seed (Nigella Sativa) on Compact Bone of Streptozotocin Induced Diabetic Rats. The Egyptian Journal of Histology. 2010;33:168 77.
  • 9. Kaleem M, Kirmani D, Asif M, Ahmed Q, Bano B. Biochemical effects of Nigella sativa L seeds in diabetic rats. Indian journal of experimental biology. 2006;44(9):745-8.
  • 10. Seker U, Kaya S, Kandemir S, Sener D, Demirel O, Nergiz Y. Effects of Black Cumin Seed Oil on Oxidative Stress and Expression of Membrane-Cytoskeleton Linker Proteins, Radixin and Moesin, in Streptozotocin Induced Diabetic Liver2022:21-6.
  • 11. Institute of Medicine Panel on Dietary A, Related C. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC): National Academies Press (US) Copyright 2000 by the National Academy of Sciences. All rights reserved.; 2000.
  • 12. Hacioglu C, Kar F, Kara Y, Yucel E, Donmez DB, Sentürk H, Kanbak G. Comparative effects of metformin and Cistus laurifolius L. extract in streptozotocin-induced diabetic rat model: oxidative, inflammatory, apoptotic, and histopathological analyzes. Environmental science and pollution research international. 2021;28(41):57888-901.
  • 13. Grzybowska M, Bober J, Olszewska M. [Metformin - mechanisms of action and use for the treatment of type 2 diabetes mellitus]. Postepy higieny i medycyny doswiadczalnej (Online). 2011;65:277-85.
  • 14. Behera SR, Sekkizhar M, Babu S. Nephro-protective Effect of Aqueous Extract of Syzygium cumini Seed on Streptozotocin Induced Diabetes in Rats. International Journal of Chemical and Lifesciences. 2019;3(2):1285-8.
  • 15. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Catechin Treatment Ameliorates Diabetes and Its Complications in Streptozotocin-Induced Diabetic Rats. Dose-response : a publication of International Hormesis Society. 2017;15(1):1559325817691158.
  • 16. Sahinturk V, Guclu C, Baycu C. Protective effects of vitamin E on ethane dimethane sulfonate-induced testicular toxicity in rats. Asian journal of andrology. 2007;9(1):117-24.
  • 17. Houcher Z, Boudiaf K, Benboubetra M, Houcher B. Effects of Methanolic Extract and Commercial Oil of Nigella sativa L. on Blood Glucose and Antioxidant Capacity in Alloxan-Induced Diabetic Rats. Pteridines. 2007;18(1):8-18.
  • 18. Rashid U, Khan MR. Phytochemicals of Periploca aphylla Dcne. ameliorated streptozotocin-induced diabetes in rat. Environmental health and preventive medicine. 2021;26(1):38.
  • 19. Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabetic medicine : a journal of the British Diabetic Association. 1997;14 (Suppl 5):S1-85.
  • 20. Mohamed J, Nazratun Nafizah AH, Zariyantey AH, Budin SB. Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation. Sultan Qaboos University medical journal. 2016;16(2):e132-41.
  • 21. El-Shemi AG, Kensara OA, Alsaegh A, Mukhtar MH. Pharmacotherapy with Thymoquinone Improved Pancreatic β-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats. Pharmacology. 2018;101(1-2):9-21.
  • 22. Li S, Huang Q, Zhang L, Qiao X, Zhang Y, Tang F, Li Z. Effect of CAPE-pNO2 against type 2 diabetes mellitus via the AMPK/GLUT4/ GSK3β/PPARα pathway in HFD/STZ-induced diabetic mice. European journal of pharmacology. 2019;853:1-10.
  • 23. Abdellatif NA. Protective Effect of Nigella Sativa Against Diabetic Complications on The Liver in White Male Rats. The Egyptian Journal of Hospital Medicine. 2013;53(1):1072-82.
  • 24. 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. Human & experimental toxicology. 2005;24(3):129-35.
  • 25. Gezginci-Oktayoglu S, Basaraner H, Yanardag R, Bolkent S. The effects of combined treatment of antioxidants on the liver injury in STZ diabetic rats. Digestive diseases and sciences. 2009;54(3):538-46.
  • 26. Balamash KS, Alkreathy HM, Al Gahdali EH, Khoja SO, Ahmad A. Comparative Biochemical and Histopathological Studies on the Efficacy of Metformin and Virgin Olive Oil against Streptozotocin-Induced Diabetes in Sprague-Dawley Rats. Journal of diabetes research. 2018;2018:4692197.
  • 27. Aktaş İ, Mehmet Gür F. Hepato-protective effects of thymoquinone and beta-aminoisobutyric acid in streptozocin induced diabetic rats. Biotechnic & histochemistry : official publication of the Biological Stain Commission. 2022;97(1):67-76.
  • 28. Abdellatif NA. Protective Effect of Nigella Sativa Against Diabetic Complications on The Liver in White Male Rats. The Egyptian Journal of Hospital Medicine. 2013;53:1072-82.
  • 29. Abdelrazek HMA, Kilany OE, Muhammad MAA, Tag HM, Abdelazim AM. Black Seed Thymoquinone Improved Insulin Secretion, Hepatic Glycogen Storage, and Oxidative Stress in Streptozotocin-Induced Diabetic Male Wistar Rats. Oxidative medicine and cellular longevity. 2018;2018:8104165.
  • 30. Daniel OO, Adeoye AO, Ojowu J, Olorunsogo OO. Inhibition of liver mitochondrial membrane permeability transition pore opening by quercetin and vitamin E in streptozotocin-induced diabetic rats. Biochemical and biophysical research communications. 2018;504(2):460-9.
There are 30 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Hayat Ayaz 0000-0002-0556-9031

Seval Kaya 0000-0001-6251-6529

Yusuf Nergiz 0000-0002-9988-9385

Project Number TIP.20.002
Publication Date August 28, 2022
Submission Date March 13, 2022
Acceptance Date May 18, 2022
Published in Issue Year 2022 Volume: 19 Issue: 2

Cite

Vancouver Ayaz H, Kaya S, Nergiz Y. Deneysel Diyabetik Sıçanlarda Metformin, E Vitamini ve Çörek Otu Yağının Karaciğer Dokusu Üzerine Hepatoprotektif Etkilerinin Karşılaştırılması. Harran Üniversitesi Tıp Fakültesi Dergisi. 2022;19(2):421-7.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty