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Investigation of Anti-inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats

Year 2024, Issue: Early Access
https://doi.org/10.18678/dtfd.1572910

Abstract

Aim: This study aimed to investigate the anti-inflammatory, antioxidative and cardioprotective effects of exercise and metformin treatment applied alone or in combination.
Material and Methods: In this study, 42 male Wistar rats were used. The rats were separated into six groups as control (CONT), exercise (EXE), 100 mg/kg metformin (M100), 200 mg/kg metformin (M200), 100 mg/kg metformin+exercise (M100+EXE), and 200 mg/kg metformin+exercise (M200+EXE). Exercise was applied for 10 weeks including exercise training. Metformin was administered 30 minutes before exercise. At the end of the study, levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), cardiac troponin-I (cTn-I), creatine kinase-muscle/brain (CK-MB), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) in serum samples from rats were quantified using the ELISA method.
Results: The combined application of metformin and exercise significantly decreased cTn-I, CK-MB, MDA, TNF-α, CRP and IL-6 levels (p<0.001). In contrast, it increased SOD, CAT, GPx, and IL-10 levels significantly (p<0.001). Glucose levels of groups treated alone or in combination were found statistically significantly less than CONT group (p<0.001).
Conclusion: The findings of this study reveal that both metformin and exercise administration, alone or in combination, exert significant anti-inflammatory, antioxidant, and cardioprotective effects in Wistar rats. These results suggest that combining metformin therapy with regular exercise may offer a synergistic approach to reducing cardiovascular risk factors and enhancing antioxidant defenses.

References

  • Luengo-Fernandez R, Little M, Gray A, Torbica A, Maggioni AP, Huculeci R, et al. Cardiovascular disease burden due to productivity losses in European Society of Cardiology countries. Eur Heart J Qual Care Clinical Outcomes. 2024;10(1):36-44.
  • Gök A, Beyazçiçek E. Experimental animal models in heart disease. Duzce Med J. 2024;26(S1):79-86.
  • Nabofa WEE, Alashe OO, Oyeyemi OT, Attah AF, Oyagbemi AA, Omobowale TO, et al. Cardioprotective effects of curcumin-nisin based poly lactic acid nanoparticle on myocardial infarction in guinea pigs. Sci Rep. 2018;8(1):16649.
  • Hemalatha KL, Stanely Mainzen Prince P. Anti-inflammatory and anti-thrombotic effects of zingerone in a rat model of myocardial infarction. Eur J Pharmacol. 2016;791:595-602.
  • Zhu P, Liu J, Shi J, Zhou Q, Liu J, Zhang X, et al. Melatonin protects ADSCs from ROS and enhances their therapeutic potency in a rat model of myocardial infarction. J Cell Mol Med. 2015;19(9):2232-43.
  • Ansari MA, Iqubal A, Ekbbal R, Haque SE. Effects of nimodipine, vinpocetine and their combination on isoproterenol-induced myocardial infarction in rats. Biomed Pharmacother. 2019;109:1372-80.
  • Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Silljé HH, et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol. 2011;301(2):H459-68.
  • Gundewar S, Calvert JW, Jha S, Toedt-Pingel I, Ji SY, Nunez D, et al. Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res. 2009;104(3):403-11.
  • Lexis CP, Wieringa WG, Hiemstra B, van Deursen VM, Lipsic E, van der Harst P, et al. Chronic metformin treatment is associated with reduced myocardial infarct size in diabetic patients with ST-segment elevation myocardial infarction. Cardiovasc Drug Ther. 2014;28(2):163-71.
  • Mellbin LG, Malmberg K, Norhammar A, Wedel H, Rydén L; DIGAMI 2 Investigators. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study. Diabetologia. 2011;54(6):1308-17.
  • Das S, Behera SK, Srinivasan A, Xavier AS, Selvarajan S, Kamalanathan S, et al. Effect of metformin on exercise capacity: a meta-analysis. Diabetes Res Clin Pract. 2018;144:270-8.
  • Steinberg JG, Ba A, Brégeon F, Delliaux S, Jammes Y. Cytokine and oxidative responses to maximal cycling exercise in sedentary subjects. Med Sci Sports Exerc. 2007;39(6):964-8.
  • Suzuki K, Totsuka M, Nakaji S, Yamada M, Kudoh S, Liu Q, et al. Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage. J Appl Physiol (1985). 1999;87(4):1360-7.
  • Zhao N, Yan QW, Xia J, Zhang XL, Li BX, Yin LY, et al. Treadmill exercise attenuates Aβ-induced mitochondrial dysfunction and enhances mitophagy activity in APP/PS1 transgenic mice. Neurochem Res. 2020;45(5):1202-14.
  • Cetinkaya A, Demir S, Orallar H, Kayacan Y, Beyazcicek E. The effects of treadmill exercise on oxidative stress in Mongolian gerbils with penicillin-induced epilepsy. Exp Biomed Res. 2018;1(1):10-16.
  • Kayacan Y, Bahadir A, Cetinkaya A, Orallar H, Cakir S, Beyazcicek E, et al. Penicillin-induced epileptiform ECoG activity in gerbils: effects of physical exercise and a Diospyros kaki extract. Neurophysiology. 2016;48(5):367-74.
  • Kaeberlein M. How healthy is the healthspan concept? Geroscience. 2018;40(4):361-4.
  • Miller BF, Thyfault JP. Exercise-pharmacology interactions: metformin, statins, and healthspan. Physiology (Bethesda). 2020;35(5):338-47.
  • Ruegsegger GN, Booth FW. Health benefits of exercise. Cold Spring Harb Perspect Med. 2018;8(7):a029694.
  • Willis BL, Gao A, Leonard D, Defina LF, Berry JD. Midlife fitness and the development of chronic conditions in later life. Arch Intern Med. 2012;172(17):1333-40.
  • Ma S, Tominaga T, Kanda K, Sugama K, Omae C, Hashimoto S, et al. Effects of an 8-week protein supplementation regimen with hyperimmunized cow milk on exercise-induced organ damage and inflammation in male runners: A randomized, placebo controlled, cross-over study. Biomedicines. 2020;8(3):51.
  • Goh J, Lim CL, Suzuki K. Effects of endurance-, strength-, and concurrent training on cytokines and inflammation. In: Schumann M, Rønnestad BR, editors. Concurrent aerobic and strength training: Scientific basics and practical applications. Springer, Cham; 2019. p.125-38.
  • Suzuki K. Characterization of exercise-induced cytokine release, the impacts on the body, the mechanisms and modulations. Int J Sports Exerc Med. 2019;5(3):122.
  • Suzuki K, Tominaga T, Ruhee RT, Ma S. Characterization and modulation of systemic inflammatory response to exhaustive exercise in relation to oxidative stress. Antioxidants (Basel). 2020;9(5):401.
  • Peake JM, Roberts LA, Figueiredo VC, Egner I, Krog S, Aas SN, et al. The effects of cold water immersion and active recovery on inflammation and cell stress responses in human skeletal muscle after resistance exercise. J Physiol. 2017;595(3):695-711.
  • Suzuki K. Cytokine response to exercise and its modulation. Antioxidants (Basel). 2018;7(1):17.
  • Iranshahy M, Rezaee R, Karimi G. Hepatoprotective activity of metformin: A new mission for an old drug? Eur J Pharmacol. 2019;850:1-7.
  • Ajzashokouhi AH, Bostan HB, Jomezadeh V, Hayes AW, Karimi G. A review on the cardioprotective mechanisms of metformin against doxorubicin. Hum Exp Toxicol. 2020;39(3):237-48.
  • Konopka AR, Esponda RR, Robinson MM, Johnson ML, Carter RE, Schiavon M, et al. Hyperglucagonemia mitigates the effect of metformin on glucose production in prediabetes. Cell Rep. 2016;15(7):1394-400.
  • Konopka AR, Laurin JL, Schoenberg HM, Reid JJ, Castor WM, Wolff CA, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. 2019;18(1):e12880.
  • Kulkarni AS, Brutsaert EF, Anghel V, Zhang K, Bloomgarden N, Pollak M, et al. Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults. Aging Cell. 2018;17(2):e12723.
  • Madiraju AK, Qiu Y, Perry RJ, Rahimi Y, Zhang XM, Zhang D, et al. Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nat Med. 2018;24(9):1384-94.
  • Triggle CR, Mohammed I, Bshesh K, Marei I, Ye K, Ding H, et al. Metformin: Is it a drug for all reasons and diseases? Metabolism. 2022;133:155223.
  • Zilinyi R, Czompa A, Czegledi A, Gajtko A, Pituk D, Lekli I, et al. The cardioprotective effect of metformin in doxorubicin-induced cardiotoxicity: the role of autophagy. Molecules. 2018;23(5):1184.
  • Kelleni MT, Amin EF, Abdelrahman AM. Effect of metformin and sitagliptin on doxorubicin-induced cardiotoxicity in rats: impact of oxidative stress, inflammation, and apoptosis. J Toxicol. 2015;2015:424813.
  • Sheta A, Elsakkar M, Hamza M, Solaiman A. Effect of metformin and sitagliptin on doxorubicin-induced cardiotoxicity in adult male albino rats. Hum Exp Toxicol. 2016;35(11):1227-39.
  • Sardu C, Paolisso P, Sacra C, Mauro C, Minicucci F, Portoghese M, et al. Effects of metformin therapy on coronary endothelial dysfunction in patients with prediabetes with stable angina and nonobstructive coronary artery stenosis: The CODYCE Multicenter Prospective Study. Diabetes Care. 2019;42(10):1946-55.
  • Xu W, Deng YY, Yang L, Zhao S, Liu J, Zhao Z, et al. Metformin ameliorates the proinflammatory state in patients with carotid artery atherosclerosis through sirtuin 1 induction. Transl Res. 2015;166(5):451-8.
  • Li J, Xu JP, Zhao XZ, Sun XJ, Xu ZW, Song SJ. Protective effect of metformin on myocardial injury in metabolic syndrome patients following percutaneous coronary intervention. Cardiology. 2014;127(2):133-9.
  • Stephenne X, Foretz M, Taleux N, van der Zon GC, Sokal E, Hue L, et al. Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia. 2011;54(12):3101-10.
  • Ouyang JY, Parakhia RA, Ochs RS. Metformin activates AMP kinase through inhibition of AMP deaminase. J Biol Chem. 2011;286(1):1-11.
  • Hammad AM, Ibrahim YA, Khdair SI, Hall FS, Alfaraj M, Jarrar Y, et al. Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1β, IL-6, IL-10 and TNF-α. Behav Brain Res. 2021;414:113475.
  • Beyazcicek O, Beyazcicek E, Kubur UB, Gok A. Effect of the combination of exercise and metformin on osteocalcin, insulin, interleukin-6, glucose levels, and body weights in rats. Niger J Clin Pract. 2024;27(6):766-73.
  • Liu J, Lu J, Zhang L, Liu Y, Zhang Y, Gao Y, et al. The combination of exercise and metformin inhibits TGF-β1/Smad pathway to attenuate myocardial fibrosis in db/db mice by reducing NF-κB-mediated inflammatory response. Biomed Pharmacother. 2023;157:114080.
  • Selvi P, Elizabeth AA. Effect of metformin on C-reactive protein in type 2 diabetes mellitus patients. J Pharm Res Int. 2021;33(23B):53-61.
  • Yu F, Xing C, Fan Y, Liu Y, Su P, Yang Q, et al. Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats. Diabetol Metab Syndr. 2023;15(1):221.
  • Shabab S, Mahmoudabady M, Gholamnezhad Z, Niazmand S, Fouladi M, Mousavi Emadi Z. Endurance exercise prevented diabetic cardiomyopathy through the inhibition of fibrosis and hypertrophy in rats. Rev Cardiovasc Med. 2024;25(5):173.
  • Özüdoğru E, Atay E, Savran M, Aşci H, Özmen Ö, Topsakal Ş. Protective effects of swimming exercises and metformin on cardiac and aortic damage caused by a high-fat diet in obese rats with type 2 diabetes, by regulating the Bcl2/Bax signaling pathway. Turk J Med Sci. 2023;53(6):1582-92.
  • Sanghani NB, Chokshi SA. Comparative study of structured physical exercise and metformin on glycemic control and body mass on obese type 2 diabetic. J Cardiovasc Dis Res. 2023;14(3):336-42.
  • Tiwari BK, Pandey KB, Abidi AB, Rizvi SI. Markers of oxidative stress during diabetes mellitus. J Biomark. 2013;2013:378790.
  • Fouladi M, Mahmoudabady M, Gholamnezhad Z, Shabab S, Niazmand S, Salmani H. Impact of endurance exercise training on biomarkers of aortic endothelial damage in diabetic rats. Cardiovasc Ther. 2024;2024(1):6025911.

Sıçanlarda Kombine Metformin ve Egzersizin Anti-inflamatuar, Antioksidatif ve Kardiyoprotektif Etkilerinin Araştırılması

Year 2024, Issue: Early Access
https://doi.org/10.18678/dtfd.1572910

Abstract

Amaç: Bu çalışmanın amacı egzersiz ve metformin tedavisinin tek başına veya birlikte uygulanmasının anti-enflamatuar, antioksidatif ve kardiyoprotektif etkilerinin araştırılmasıdır.
Gereç ve Yöntemler: Bu çalışmada 42 adet erkek Wistar sıçan kullanılmıştır. Sıçanlar kontrol (CONT), egzersiz (EXE), 100 mg/kg metformin (M100), 200 mg/kg metformin (M200), 100 mg/kg metformin+egzersiz (M100+EXE) ve 200 mg/kg metformin+egzersiz (M200+EXE) olmak üzere altı gruba ayrılmıştır. Egzersiz, egzersiz eğitimi de dahil olmak üzere 10 hafta boyunca uygulanmıştır. Metformin egzersizden 30 dakika önce uygulanmıştır. Çalışma sonunda sıçanlardan alınan serum örneklerinde, C-reaktif protein (CRP), tümör nekroz faktörü-alfa (TNF-α), interlökin-6 (IL-6), interlökin-10 (IL-10), kardiyak troponin-I (cTn-I), kreatin kinaz-kas/beyin (CK-MB), katalaz (CAT), süperoksit dismutaz (SOD), glutatyon peroksidaz (GPx) ve malondialdehit (MDA) ELISA yöntemi kullanılarak ölçülmüştür.
Bulgular: Metformin ve egzersizin birlikte uygulanması cTn-I, CK-MB, MDA, TNF-α, CRP ve IL-6 düzeylerini anlamlı şekilde azaltmıştır (p<0,001). Buna karşılık, SOD, CAT, GPx ve IL-10 düzeylerini de önemli şekilde artırmıştır (p<0,001). Tek başına veya kombinasyon halinde tedavi edilen grupların glukoz seviyeleri CONT grubundan istatistiksel olarak anlamlı şekilde daha düşük bulunmuştur (p<0,001).
Sonuç: Bu çalışmanın bulguları, hem metformin hem de egzersiz uygulamasının, tek başına veya kombinasyon halinde, Wistar sıçanlarında önemli anti-inflamatuar, antioksidan ve kardiyoprotektif etkiler gösterdiğini ortaya koymaktadır. Bu sonuçlar, metformin tedavisinin düzenli egzersizle birleştirilmesinin, kardiyovasküler risk faktörlerini azaltmak ve antioksidan savunmaları güçlendirmek için sinerjik bir yaklaşım sunabileceğini düşündürmektedir.

References

  • Luengo-Fernandez R, Little M, Gray A, Torbica A, Maggioni AP, Huculeci R, et al. Cardiovascular disease burden due to productivity losses in European Society of Cardiology countries. Eur Heart J Qual Care Clinical Outcomes. 2024;10(1):36-44.
  • Gök A, Beyazçiçek E. Experimental animal models in heart disease. Duzce Med J. 2024;26(S1):79-86.
  • Nabofa WEE, Alashe OO, Oyeyemi OT, Attah AF, Oyagbemi AA, Omobowale TO, et al. Cardioprotective effects of curcumin-nisin based poly lactic acid nanoparticle on myocardial infarction in guinea pigs. Sci Rep. 2018;8(1):16649.
  • Hemalatha KL, Stanely Mainzen Prince P. Anti-inflammatory and anti-thrombotic effects of zingerone in a rat model of myocardial infarction. Eur J Pharmacol. 2016;791:595-602.
  • Zhu P, Liu J, Shi J, Zhou Q, Liu J, Zhang X, et al. Melatonin protects ADSCs from ROS and enhances their therapeutic potency in a rat model of myocardial infarction. J Cell Mol Med. 2015;19(9):2232-43.
  • Ansari MA, Iqubal A, Ekbbal R, Haque SE. Effects of nimodipine, vinpocetine and their combination on isoproterenol-induced myocardial infarction in rats. Biomed Pharmacother. 2019;109:1372-80.
  • Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Silljé HH, et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol. 2011;301(2):H459-68.
  • Gundewar S, Calvert JW, Jha S, Toedt-Pingel I, Ji SY, Nunez D, et al. Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res. 2009;104(3):403-11.
  • Lexis CP, Wieringa WG, Hiemstra B, van Deursen VM, Lipsic E, van der Harst P, et al. Chronic metformin treatment is associated with reduced myocardial infarct size in diabetic patients with ST-segment elevation myocardial infarction. Cardiovasc Drug Ther. 2014;28(2):163-71.
  • Mellbin LG, Malmberg K, Norhammar A, Wedel H, Rydén L; DIGAMI 2 Investigators. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study. Diabetologia. 2011;54(6):1308-17.
  • Das S, Behera SK, Srinivasan A, Xavier AS, Selvarajan S, Kamalanathan S, et al. Effect of metformin on exercise capacity: a meta-analysis. Diabetes Res Clin Pract. 2018;144:270-8.
  • Steinberg JG, Ba A, Brégeon F, Delliaux S, Jammes Y. Cytokine and oxidative responses to maximal cycling exercise in sedentary subjects. Med Sci Sports Exerc. 2007;39(6):964-8.
  • Suzuki K, Totsuka M, Nakaji S, Yamada M, Kudoh S, Liu Q, et al. Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage. J Appl Physiol (1985). 1999;87(4):1360-7.
  • Zhao N, Yan QW, Xia J, Zhang XL, Li BX, Yin LY, et al. Treadmill exercise attenuates Aβ-induced mitochondrial dysfunction and enhances mitophagy activity in APP/PS1 transgenic mice. Neurochem Res. 2020;45(5):1202-14.
  • Cetinkaya A, Demir S, Orallar H, Kayacan Y, Beyazcicek E. The effects of treadmill exercise on oxidative stress in Mongolian gerbils with penicillin-induced epilepsy. Exp Biomed Res. 2018;1(1):10-16.
  • Kayacan Y, Bahadir A, Cetinkaya A, Orallar H, Cakir S, Beyazcicek E, et al. Penicillin-induced epileptiform ECoG activity in gerbils: effects of physical exercise and a Diospyros kaki extract. Neurophysiology. 2016;48(5):367-74.
  • Kaeberlein M. How healthy is the healthspan concept? Geroscience. 2018;40(4):361-4.
  • Miller BF, Thyfault JP. Exercise-pharmacology interactions: metformin, statins, and healthspan. Physiology (Bethesda). 2020;35(5):338-47.
  • Ruegsegger GN, Booth FW. Health benefits of exercise. Cold Spring Harb Perspect Med. 2018;8(7):a029694.
  • Willis BL, Gao A, Leonard D, Defina LF, Berry JD. Midlife fitness and the development of chronic conditions in later life. Arch Intern Med. 2012;172(17):1333-40.
  • Ma S, Tominaga T, Kanda K, Sugama K, Omae C, Hashimoto S, et al. Effects of an 8-week protein supplementation regimen with hyperimmunized cow milk on exercise-induced organ damage and inflammation in male runners: A randomized, placebo controlled, cross-over study. Biomedicines. 2020;8(3):51.
  • Goh J, Lim CL, Suzuki K. Effects of endurance-, strength-, and concurrent training on cytokines and inflammation. In: Schumann M, Rønnestad BR, editors. Concurrent aerobic and strength training: Scientific basics and practical applications. Springer, Cham; 2019. p.125-38.
  • Suzuki K. Characterization of exercise-induced cytokine release, the impacts on the body, the mechanisms and modulations. Int J Sports Exerc Med. 2019;5(3):122.
  • Suzuki K, Tominaga T, Ruhee RT, Ma S. Characterization and modulation of systemic inflammatory response to exhaustive exercise in relation to oxidative stress. Antioxidants (Basel). 2020;9(5):401.
  • Peake JM, Roberts LA, Figueiredo VC, Egner I, Krog S, Aas SN, et al. The effects of cold water immersion and active recovery on inflammation and cell stress responses in human skeletal muscle after resistance exercise. J Physiol. 2017;595(3):695-711.
  • Suzuki K. Cytokine response to exercise and its modulation. Antioxidants (Basel). 2018;7(1):17.
  • Iranshahy M, Rezaee R, Karimi G. Hepatoprotective activity of metformin: A new mission for an old drug? Eur J Pharmacol. 2019;850:1-7.
  • Ajzashokouhi AH, Bostan HB, Jomezadeh V, Hayes AW, Karimi G. A review on the cardioprotective mechanisms of metformin against doxorubicin. Hum Exp Toxicol. 2020;39(3):237-48.
  • Konopka AR, Esponda RR, Robinson MM, Johnson ML, Carter RE, Schiavon M, et al. Hyperglucagonemia mitigates the effect of metformin on glucose production in prediabetes. Cell Rep. 2016;15(7):1394-400.
  • Konopka AR, Laurin JL, Schoenberg HM, Reid JJ, Castor WM, Wolff CA, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. 2019;18(1):e12880.
  • Kulkarni AS, Brutsaert EF, Anghel V, Zhang K, Bloomgarden N, Pollak M, et al. Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults. Aging Cell. 2018;17(2):e12723.
  • Madiraju AK, Qiu Y, Perry RJ, Rahimi Y, Zhang XM, Zhang D, et al. Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nat Med. 2018;24(9):1384-94.
  • Triggle CR, Mohammed I, Bshesh K, Marei I, Ye K, Ding H, et al. Metformin: Is it a drug for all reasons and diseases? Metabolism. 2022;133:155223.
  • Zilinyi R, Czompa A, Czegledi A, Gajtko A, Pituk D, Lekli I, et al. The cardioprotective effect of metformin in doxorubicin-induced cardiotoxicity: the role of autophagy. Molecules. 2018;23(5):1184.
  • Kelleni MT, Amin EF, Abdelrahman AM. Effect of metformin and sitagliptin on doxorubicin-induced cardiotoxicity in rats: impact of oxidative stress, inflammation, and apoptosis. J Toxicol. 2015;2015:424813.
  • Sheta A, Elsakkar M, Hamza M, Solaiman A. Effect of metformin and sitagliptin on doxorubicin-induced cardiotoxicity in adult male albino rats. Hum Exp Toxicol. 2016;35(11):1227-39.
  • Sardu C, Paolisso P, Sacra C, Mauro C, Minicucci F, Portoghese M, et al. Effects of metformin therapy on coronary endothelial dysfunction in patients with prediabetes with stable angina and nonobstructive coronary artery stenosis: The CODYCE Multicenter Prospective Study. Diabetes Care. 2019;42(10):1946-55.
  • Xu W, Deng YY, Yang L, Zhao S, Liu J, Zhao Z, et al. Metformin ameliorates the proinflammatory state in patients with carotid artery atherosclerosis through sirtuin 1 induction. Transl Res. 2015;166(5):451-8.
  • Li J, Xu JP, Zhao XZ, Sun XJ, Xu ZW, Song SJ. Protective effect of metformin on myocardial injury in metabolic syndrome patients following percutaneous coronary intervention. Cardiology. 2014;127(2):133-9.
  • Stephenne X, Foretz M, Taleux N, van der Zon GC, Sokal E, Hue L, et al. Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia. 2011;54(12):3101-10.
  • Ouyang JY, Parakhia RA, Ochs RS. Metformin activates AMP kinase through inhibition of AMP deaminase. J Biol Chem. 2011;286(1):1-11.
  • Hammad AM, Ibrahim YA, Khdair SI, Hall FS, Alfaraj M, Jarrar Y, et al. Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1β, IL-6, IL-10 and TNF-α. Behav Brain Res. 2021;414:113475.
  • Beyazcicek O, Beyazcicek E, Kubur UB, Gok A. Effect of the combination of exercise and metformin on osteocalcin, insulin, interleukin-6, glucose levels, and body weights in rats. Niger J Clin Pract. 2024;27(6):766-73.
  • Liu J, Lu J, Zhang L, Liu Y, Zhang Y, Gao Y, et al. The combination of exercise and metformin inhibits TGF-β1/Smad pathway to attenuate myocardial fibrosis in db/db mice by reducing NF-κB-mediated inflammatory response. Biomed Pharmacother. 2023;157:114080.
  • Selvi P, Elizabeth AA. Effect of metformin on C-reactive protein in type 2 diabetes mellitus patients. J Pharm Res Int. 2021;33(23B):53-61.
  • Yu F, Xing C, Fan Y, Liu Y, Su P, Yang Q, et al. Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats. Diabetol Metab Syndr. 2023;15(1):221.
  • Shabab S, Mahmoudabady M, Gholamnezhad Z, Niazmand S, Fouladi M, Mousavi Emadi Z. Endurance exercise prevented diabetic cardiomyopathy through the inhibition of fibrosis and hypertrophy in rats. Rev Cardiovasc Med. 2024;25(5):173.
  • Özüdoğru E, Atay E, Savran M, Aşci H, Özmen Ö, Topsakal Ş. Protective effects of swimming exercises and metformin on cardiac and aortic damage caused by a high-fat diet in obese rats with type 2 diabetes, by regulating the Bcl2/Bax signaling pathway. Turk J Med Sci. 2023;53(6):1582-92.
  • Sanghani NB, Chokshi SA. Comparative study of structured physical exercise and metformin on glycemic control and body mass on obese type 2 diabetic. J Cardiovasc Dis Res. 2023;14(3):336-42.
  • Tiwari BK, Pandey KB, Abidi AB, Rizvi SI. Markers of oxidative stress during diabetes mellitus. J Biomark. 2013;2013:378790.
  • Fouladi M, Mahmoudabady M, Gholamnezhad Z, Shabab S, Niazmand S, Salmani H. Impact of endurance exercise training on biomarkers of aortic endothelial damage in diabetic rats. Cardiovasc Ther. 2024;2024(1):6025911.
There are 51 citations in total.

Details

Primary Language English
Subjects Medical Physiology (Other)
Journal Section Research Article
Authors

Özge Beyazçiçek 0000-0002-8617-4380

Ersin Beyazçiçek 0000-0002-6817-4512

Ali Gök 0000-0003-4103-9537

Murat Tekbaş 0000-0002-6246-7541

Halit Diril 0000-0003-4409-8268

Şerif Demir 0000-0002-0305-5758

Early Pub Date December 20, 2024
Publication Date
Submission Date October 24, 2024
Acceptance Date December 12, 2024
Published in Issue Year 2024 Issue: Early Access

Cite

APA Beyazçiçek, Ö., Beyazçiçek, E., Gök, A., Tekbaş, M., et al. (2024). Investigation of Anti-inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats. Duzce Medical Journal(Early Access). https://doi.org/10.18678/dtfd.1572910
AMA Beyazçiçek Ö, Beyazçiçek E, Gök A, Tekbaş M, Diril H, Demir Ş. Investigation of Anti-inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats. Duzce Med J. December 2024;(Early Access). doi:10.18678/dtfd.1572910
Chicago Beyazçiçek, Özge, Ersin Beyazçiçek, Ali Gök, Murat Tekbaş, Halit Diril, and Şerif Demir. “Investigation of Anti-Inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats”. Duzce Medical Journal, no. Early Access (December 2024). https://doi.org/10.18678/dtfd.1572910.
EndNote Beyazçiçek Ö, Beyazçiçek E, Gök A, Tekbaş M, Diril H, Demir Ş (December 1, 2024) Investigation of Anti-inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats. Duzce Medical Journal Early Access
IEEE Ö. Beyazçiçek, E. Beyazçiçek, A. Gök, M. Tekbaş, H. Diril, and Ş. Demir, “Investigation of Anti-inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats”, Duzce Med J, no. Early Access, December 2024, doi: 10.18678/dtfd.1572910.
ISNAD Beyazçiçek, Özge et al. “Investigation of Anti-Inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats”. Duzce Medical Journal Early Access (December 2024). https://doi.org/10.18678/dtfd.1572910.
JAMA Beyazçiçek Ö, Beyazçiçek E, Gök A, Tekbaş M, Diril H, Demir Ş. Investigation of Anti-inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats. Duzce Med J. 2024. doi:10.18678/dtfd.1572910.
MLA Beyazçiçek, Özge et al. “Investigation of Anti-Inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats”. Duzce Medical Journal, no. Early Access, 2024, doi:10.18678/dtfd.1572910.
Vancouver Beyazçiçek Ö, Beyazçiçek E, Gök A, Tekbaş M, Diril H, Demir Ş. Investigation of Anti-inflammatory, Antioxidative, and Cardioprotective Effects of Combined Metformin and Exercise in Rats. Duzce Med J. 2024(Early Access).