Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction

Ceylan Verda Bitirim; Yusuf Olgar; Deniz Billur; Kamil Akçalı; Belma Turan

doi:10.4274/atfm.galenos.2021.43760

Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction

Abstract

Objectives: Overfeeding with a high carbohydrate and/or high-fat diet induces metabolic syndrome (MetS) in humans, which is characterized by insulin-resistance. Long life span leads to increases in the ratio of aged humans in populations and an important percentage of the aged humans has insulin-resistance. There is a close relationship between insulin resistance and cardiac dysfunction, at least, via uncontrolled production of reactive oxygen species, while mitochondrial dysfunction plays an important role in that relation. To explore that relation, we aimed to examine the possible cardioprotective effect of a mitochondria-targeting antioxidant by using electrophysiological and histological examinations. Materials and Methods: We used Wistar male rats in three groups as; those that were 24-month-old (elderly group; n=7), adults fed with 32% sucrose diet (MetS-group; 6-month-old; n=7), and adults fed with standard food (Control group; 6-month-old, n=7). MetS was confirmed with high blood glucose, oral glucose tolerance test, and serum insulin levels. Cardiomyocytes either treated with an antioxidant MitoTEMPO were isolated from the left ventricle by enzymatic method, and the ultrastructure and function of mitochondria as well as adenosine triphosphate (ATP)-dependent K+-channel currents (IKATP; patch-clamp technique) were evaluated. Results: There were marked increases in the fragmentation of mitochondria, depolarization in the membrane potential, and the production of ROS in insulin-resistant cardiomyocytes. There were significant decreases in IKATP and ATP level (p<0.05) in the aged-cardiomyocytes. Incubation of those insulin-resistant or aged-cardiomyocytes with a mitochondria-targeting antioxidant MitoTEMPO (0.1 μM, 4-5 h at 37°C) provided marked reverses in those parameters. Conclusion: Overall, the present data strongly indicate that mitochondria-targeting antioxidant application can exert cardioprotective effects in either insulin-resistant MetS or aged mammalians, providing strong implications on mitochondria as a novel strategy for prevention/treatment of cardiovascular diseases.

Keywords

Ethical Statement

Etik Kurul Onayı: Etik onayı Ankara Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu’ndan alınmıştır (Karar no: 2016-18-165, tarih: 21.09.2016). Hasta Onayı: Bu çalışmada bir hayvan deneyi çalışması olduğundan hasta onayı alınmamıştır. Hakem Değerlendirmesi: Editörler kurulunun dışından olan kişiler tarafından değerlendirilmiştir. Yazarlık Katkıları Konsept: B.T., K.C.A., Dizayn: B.T., Veri Toplama veya İşleme: C.V.B., Y.O., D.B., Analiz veya Yorumlama: C.V.B., Y.O., D.B., B.T., K.C.A., Literatür Arama: C.V.B., Y.O., Yazan: B.T. Çıkar Çatışması: Yazarlar tarafından çıkar çatışması bildirilmemiştir. Finansal Destek: Bu çalışmanın finansal desteği, TÜBİTAK SBAG-216S979 nolu projeden sağlanmıştır.

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Details

Primary Language

English

Subjects

Histology and Embryology

Journal Section

Research Article

Authors

Ceylan Verda Bitirim ^*
0000-0002-7979-0679
Türkiye

Yusuf Olgar This is me
0000-0002-3226-7450
Türkiye

Deniz Billur This is me
0000-0001-8541-8251
Türkiye

Kamil Akçalı This is me
0000-0002-7816-6938
Türkiye

Belma Turan This is me
0000-0003-2583-9294
Türkiye

Publication Date

August 31, 2021

Submission Date

March 4, 2021

Acceptance Date

March 23, 2021

Published in Issue

Year 2021 Volume: 74 Number: 2

DOI

https://doi.org/10.4274/atfm.galenos.2021.43760

IZ

https://izlik.org/JA76JR24MA

Cite

RIS / Bibtex

APA

Bitirim, C. V., Olgar, Y., Billur, D., Akçalı, K., & Turan, B. (2021). Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 74(2), 252-258. https://doi.org/10.4274/atfm.galenos.2021.43760

AMA

1.Bitirim CV, Olgar Y, Billur D, Akçalı K, Turan B. Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2021;74(2):252-258. doi:10.4274/atfm.galenos.2021.43760

Chicago

Bitirim, Ceylan Verda, Yusuf Olgar, Deniz Billur, Kamil Akçalı, and Belma Turan. 2021. “Beneficial Effect of a Mitochondrial-Targeted Antioxidant Mitotempo in Insulin-Resistant Mammalian Cardiac Dysfunction”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 74 (2): 252-58. https://doi.org/10.4274/atfm.galenos.2021.43760.

EndNote

Bitirim CV, Olgar Y, Billur D, Akçalı K, Turan B (August 1, 2021) Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası 74 2 252–258.

IEEE

[1]C. V. Bitirim, Y. Olgar, D. Billur, K. Akçalı, and B. Turan, “Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 74, no. 2, pp. 252–258, Aug. 2021, doi: 10.4274/atfm.galenos.2021.43760.

ISNAD

Bitirim, Ceylan Verda - Olgar, Yusuf - Billur, Deniz - Akçalı, Kamil - Turan, Belma. “Beneficial Effect of a Mitochondrial-Targeted Antioxidant Mitotempo in Insulin-Resistant Mammalian Cardiac Dysfunction”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 74/2 (August 1, 2021): 252-258. https://doi.org/10.4274/atfm.galenos.2021.43760.

JAMA

1.Bitirim CV, Olgar Y, Billur D, Akçalı K, Turan B. Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2021;74:252–258.

MLA

Bitirim, Ceylan Verda, et al. “Beneficial Effect of a Mitochondrial-Targeted Antioxidant Mitotempo in Insulin-Resistant Mammalian Cardiac Dysfunction”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 74, no. 2, Aug. 2021, pp. 252-8, doi:10.4274/atfm.galenos.2021.43760.

Vancouver

1.Ceylan Verda Bitirim, Yusuf Olgar, Deniz Billur, Kamil Akçalı, Belma Turan. Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2021 Aug. 1;74(2):252-8. doi:10.4274/atfm.galenos.2021.43760

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