Top

Published in:

27-01-2023

Fullerene C₆₀ Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats

Authors: Seda Beyaz, Abdullah Aslan, Ozlem Gok, Can Ali Agca, Ibrahim Hanifi Ozercan

Published in: Cardiovascular Toxicology | Issue 2/2023

Abstract

The present study aimed to investigate the therapeutic effect of fullerene C₆₀ nanoparticle against heart tissue damage caused by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Female Wistar albino rats, 8 weeks old (n = 60) weighing around (150 ± 10 g) were used for the study. These rats were divided into 4 groups and each group included 15 rats. Groups: (i) Control Group: Fed with standard diet; (ii) C₆₀ Group: C₆₀ (1.7 mg/kg bw, oral gavage); (iii) DMBA Group: DMBA (45 mg/kg bw, oral gavage); (iv) C₆₀ and DMBA Group: C₆₀ (1.7 mg/kg bw, oral gavage) and DMBA (45 mg/kg bw, oral gavage) group. Malondialdehyde (MDA) analysis, catalase activity (CAT), and glutathione (GSH) in heart tissue were determined by spectrophotometer. In addition, heart tissue DNA damage was investigated. Caspase-3, p53, HO-1, COX-2, and TNF-α protein expression levels in heart tissue were determined by western blotting. As a result, Caspase-3, p53, HO-1 protein expression, GSH levels and CAT activity increased, COX-2, TNF-α protein expression, and MDA levels were significantly decreased in the C₆₀ + DMBA group compared to the DMBA group. Therefore, the fullerene C₆₀ nanoparticle may be a promising and effective therapy for the treatment of heart diseases associated with inflammation.

Garimella, R., & Eltorai, A. E. (2017). Nanotechnology in orthopedics. Journal Orthopaedic, 14(1), 30–33.CrossRef

Prylutska, S., Grynyuk, I., Matyshevska, O., Prylutskyy, Y., Evstigneev, M., Scharff, P., & Ritter, U. (2014). C₆₀ fullerene as synergistic agent in tumor-inhibitory doxorubicin treatment. Drugs in R&D, 14, 333–340.CrossRef

Folkmann, J. K., Risom, L., Jacobsen, N. R., Wallin, H., Loft, S., & Moller, P. (2009). Oxidatively damaged DNA in rats exposed by oral gavage to C₆₀ fullerenes and single-walled carbon nanotubes. Environmental Health Perspectives, 117(5), 703–708.CrossRefPubMed

Grebinyk, A., Grebinyk, S., Prylutska, S., Ritter, U., Matyshevska, O., Dandekar, T., & Frohme, M. (2018). C₆₀ fullerene accumulation in human leukemic cells and perspectives of LED-mediated photodynamic therapy. Free Radical Biology and Medicine, 124, 319–327.CrossRefPubMed

Franskevych, D. V., Prylutska, S. V., Grynyuk, I. I., Grebinyk, D. M., & Matyshevska, O. P. (2015). Enhanced cytotoxicity of photoexcited fullerene C₆₀ and cisplatin combination against drug resistant leukemic cells. Experimental Oncology, 37(3), 187–191.CrossRefPubMed

Andrievsky, G. V., Bruskov, V. I., Tykhomyrov, A. A., & Gudkov, S. V. (2009). Peculiarities of the antioxidant and radioprotective effects of hydrated C₆₀ fullerene nanostuctures in vitro and in vivo. Free Radical Biology and Medicine, 47, 786–793.CrossRefPubMed

Elshater, A. E. A., Haridy, M. A. M., Salman, M. M. A., Fayyad, A. S., & Hammad, S. (2018). Fullerene C₆₀ nanoparticles ameliorated cyclophosphamide-induced acute hepatotoxicity in rats. Biomedicine & Pharmacotherapy, 97, 53–59.CrossRef

Rengarajan, T., Nandakumar, N., Rajendran, P., Ganesh, M. K., Balasubramanian, M. P., & Nishigaki, I. (2015). D-Pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB. Journal of Physiology and Biochemistry, 71(2), 191–204.CrossRefPubMed

Asadi, M., Taghizadeh, S., Kaviani, E., Vakili, O., Taheri‐Anganeh, M., Tahamtan, M., & Savardashtaki, A. (2021). Caspase‐3: Structure, function, and biotechnological aspects. Biotechnology and Applied Biochemistry, 1–13.

10.

Barabutis, N., Schally, A. V., & Siejka, A. (2018). p53, GHRH, inflammation and cancer. eBioMedicine, 37, 557–562.CrossRefPubMedPubMedCentral

11.

Naito, Y., Takagi, T., & Higashimura, Y. (2014). Heme oxygenase-1 and anti-inflammatory M2 macrophages. Archives of Biochemistry and Biophysics, 564, 83–88.CrossRefPubMed

12.

Orkan, G. (2016). Diagnostic utility of immunohistochemical COX-2, p53, CD10 and E-cadherin expression in colorectal adenomas and carcinomas. Medicine Thesis, Necmettin Erbakan Univ. Konya, Turkey.

13.

Varfolomeev, E., & Vucic, D. (2018). Intracellular regulation of TNF activity in health and disease. Cytokine, 101, 26–32.CrossRefPubMed

14.

Hamam, H. (2019). Determination of some antioxidant activities (superoxide dismutase, catalase, and reducing glutathione) and oxidative stress level (malondialdehyde acid) in cirrhotic liver patients. Master Thesis, Van Yuzuncu Yıl Univ. Van, Turkey.

15.

Lv, H., Zhen, C., Liu, J., Yang, P., Hu, L., & Shang, P. (2019). Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2019/3150145CrossRefPubMedPubMedCentral

16.

Nitta, Y., Muraoka-Hirayama, S., & Sakurai, K. (2020). Catalase is required for peroxisome maintenance during adipogenesis. Biochimica et Biophysica Acta(BBA) - Molecular and Cell Biology of Lipids, 18, 1–12.

17.

Sheokand, S., Navik, U., & Bansal, A. K. (2019). Nanocrystalline solid dispersions (NSD) of hesperetin (HRN) for prevention of 7,12-dimethylbenz [a] anthracene (DMBA)-induced breast cancer in sprague-dawley (sd) rats. European Journal of Pharmaceutical Sciences, 128, 240–249.CrossRefPubMed

18.

Beyaz, S. (2021). The investigation of protective effects of fullerene C₆₀ nanoparticle against to breast cancer by in vi̇vo, in vitro and in silico analysis, Doctoral Thesis, Firat Univ. Elazig, Turkey

19.

Baati, T., Bourasset, F., Gharbi, N., Njim, L., Abderrabba, M., Kerkeni, A., Szwarc, H., & Moussa, F. (2012). The prolongation of the lifespan of rats by repeated oral administration of [60] fullerene. Biomaterials, 33(19), 4936–4946.CrossRefPubMed

20.

Caliskan, A.M. (2009). Effect of acamprosate on alcohol dependence, brain glutathione, glutathione peroxydase, malondialdehid, Ca+2 -ATPase and NMDA receptors of rats. Medicine Thesis, Suleyman Demirel Univ. Isparta, Turkey.

21.

Aslan, A., Beyaz, S., Gok, O., & Erman, O. (2020). The effect of ellagic acid on caspase-3/Bcl-2/Nrf-2/NF-κB/TNF-α/COX-2 gene expression product apoptosis pathway: A new approach for muscle damage therapy. Molecular Biology Reports, 47, 2573–2582.CrossRefPubMed

22.

Aslan, A., Gok, O., Beyaz, S., Arslan, E., Erman, O., & Agca, C. A. (2020). The preventive effect of ellagic acid on brain damage in rats via regulating of Nrf-2, NF-κB and apoptotic pathway. Journal of Food Biochemistry, 44, e13217.CrossRefPubMed

23.

Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680–685.CrossRefPubMed

24.

Aslan, A., Can, M. I., Gok, O., Beyaz, S., Parlak, G., & Ozercan, I. H. (2022). The inducing of caspase and bcl-2 pathway with royal jelly decreases the muscle tissue damage exposed with fluoride in rats. Environmental Science and Pollution Research, 29, 10547–10557.CrossRefPubMed

25.

Aslan, A., Gok, O., Beyaz, S., Can, M. I., Parlak, G., Gundogdu, R., Ozercan, I. H., & Baspinar, S. (2022). Royal jelly regulates the caspase, Bax and COX-2, TNF-α protein pathways in the fluoride exposed lung damage in rats. Tissue and Cell, 76, 101754.CrossRefPubMed

26.

Aebi, H. (1974). Catalase. In U. Bergmeyer (Ed.), Methods of enzymatic analysis (pp. 673–677). Academic Press.CrossRef

27.

Aslan, A., Gok, O., Beyaz, S., Uslu, H., Erman, F., Erman, O., & Baspinar, S. (2022). Ellagic acid inhibits proinflammatory intermediary manufacture by suppressing NF-κB/Akt, VEGF and activating Nrf-2/Caspase-3 signaling pathways in rat testicular damage: A new way for testicular damage cure and in silico approach. Toxicology Mechanisms and Methods, 32(6), 463–476.CrossRefPubMed

28.

Aslan, A. (2011). The effect of lycopene on the cyclooxygenase (COX-2), caspase-3, caspase-9, Bax, Bcl-2, p53 protein expression and DNA damage in rats with azoxhymethane-induced colorectal cancer. Doctoral Thesis, Firat Univ. Elazig, Turkey.

29.

Beyaz, S., Aslan, A., Gok, O., Uslu, H., Agca, C. A., & Ozercan, I. H. (2022). In vivo, in vitro and in silico anticancer investigation of fullerene C₆₀ on DMBA induced breast cancer in rats. Life Sciences, 291, 120281.CrossRefPubMed

30.

Kepinska, M., Kizek, R., & Milnerowicz, H. (2018). Metallothionein and superoxide dismutase antioxidative protein status in fullerene-doxorubicin delivery to MCF-7 human breast cancer cells. International Journal of Molecular Sciences, 19(3253), 2–17.

31.

Injac, R., Perse, M., Cerne, M., Potocnik, N., Radic, N., Govedarica, B., Djordjevic, A., Cerar, A., & Strukelj, B. (2009). Protective effects of fullerenol C₆₀(OH)₂₄ against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer. Biomaterials, 30(6), 1184–1196.CrossRefPubMed

32.

Gudkov, S. V., Guryev, E. L., Gapeyev, A. B., Sharapov, M. G., Bunkin, N. F., Shkirin, A. V., Zabelina, T. S., Glinushkin, A. P., Sevenostyanov, M. A., Belosludtsev, K. N., Chernikov, A. V., Bruskov, V. I., & Zvyagin, A. V. (2019). Unmodified hydrated C₆₀ fullerene molecules exhibit antioxidant properties, prevent damage to DNA and proteins induced by reactive oxygen species and protect mice against injuries caused by radiation-induced oxidative stress. Nanomedicine: Nanotechnology, Biology and Medicine, 15(1), 37–46.CrossRefPubMed

33.

Klein, A. L., Imazio, M., Brucato, A., Cremer, P., LeWinter, M., Abbate, A., Lin, D., Martini, A., Beutler, A., Chang, S., Fang, F., Gervais, A., Perrin, R., & Paolini, J. F. (2020). RHAPSODY: Rationale for and design of a pivotal phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β trap, in patients with recurrent pericarditis. American Heart Journal, 228, 81–90.CrossRefPubMed

34.

Aslan, A., Hussein, Y. T., Gok, O., Beyaz, S., Erman, O., & Baspinar, S. (2020). Ellagic acid ameliorates lung damage in rats via modulating antioxidant activities, inhibitory effects on inflammatory mediators and apoptosis inducing activities. Environmental Science and Pollution Research, 27, 7526–7537.CrossRefPubMed

35.

Hao, T., Zhou, J., Lü, S., Yang, B., Wang, Y., Fang, W., Jiang, X., Lin, Q., Li, J., & Wang, C. (2016). Fullerene mediates proliferation and cardiomyogenic differentiation of adipose-derived stem cells via modulation of MAPK pathway and cardiac protein expression. International Journal of Nanomedicine, 11, 269.PubMedPubMedCentral

36.

Aly, F. M., Othman, A., & Haridy, M. A. (2018). Protective effects of fullerene C₆₀ nanoparticles and virgin olive oil against genotoxicity induced by cyclophosphamide in rats. Oxidative Medicine Cellular Longevity, 2018, 1–12.CrossRef

37.

Torres, V. M., Srdjenovic, B., Jacevic, V., Simic, V. D., Djordjevic, A., & Simplício, A. L. (2010). Fullerenol C₆₀ (OH)₂₄ prevents doxorubicin-induced acute cardiotoxicity in rats. Pharmacological Reports, 62(4), 707–718.CrossRefPubMed

38.

Yu, H., Chen, B., & Ren, Q. (2019). Baicalin relieves hypoxia-aroused H9c2 cell apoptosis by activating Nrf2/HO-1-mediated HIF1α/BNIP3 pathway. Artificial Cells Nanomedicine and Biotechnology, 47(1), 3657–3663.CrossRefPubMed

39.

Shan, H., Li, T., Zhang, L., Yang, R., Li, Y., Zhang, M., Dong, Y., Zhou, Y., Xu, C., Yang, B., Liang, H., Gao, X., & Shan, H. (2019). Heme oxygenase-1 prevents heart against myocardial infarction by attenuating ischemic injury-induced cardiomyocytes senescence. eBioMedicine, 39, 59–68.CrossRefPubMed

40.

Fathi, R., Nasiri, K., Akbari, A., Ahmadi-KaniGolzar, F., & Farajtabar, Z. (2020). Exercise protects against ethanol-induced damage in rat heart and liver through the inhibition of apoptosis and activation of Nrf-2/Keap-1/HO-1 pathway. Life Sciences, 256, 117958.CrossRefPubMed

41.

Amirshahi, N., Alyautdin, R. N., Sarkar, S., Rezayat, S. M., Orlova, M. A., Trushkov, I. V., Buchachenko, A. L., & Kuznetsov, D. A. (2008). Fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C₆₀) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle. Archives of Medical Research, 39(6), 549–559.CrossRefPubMed

42.

Adeli, S., Zarrindast, M. R., Niknahad, H., Sarkar, S., Bidgoli, S. A., Korani, M., Ghasemzadeh, P., & Rezayat, S. M. (2012). Protective effects of a magnesium magnetic isotope (Mg²⁵)-exchanging nanoparticle (²⁵MgPMC₁₆) on mitochondrial functional disorders in esmolol-induced cardiac arrest in rats. Autonomic Autacoid Pharmacology, 32(1–2), 1–7.CrossRefPubMed

Title: Fullerene C60 Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats
Authors: Seda Beyaz
Abdullah Aslan
Ozlem Gok
Can Ali Agca
Ibrahim Hanifi Ozercan
Publication date: 27-01-2023
Publisher: Springer US
Published in: Cardiovascular Toxicology / Issue 2/2023
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-023-09780-y

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Fullerene C₆₀ Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2023

Influence of ZFHX3 Polymorphisms on the Risk of Ischemic Stroke in Chinese Han Population

Protective Effect of Sevoflurane Preconditioning on Cardiomyocytes Against Hypoxia/Reoxygenation Injury by Modulating Iron Homeostasis and Ferroptosis

Metformin and Dapagliflozin Attenuate Doxorubicin-Induced Acute Cardiotoxicity in Wistar Rats: An Electrocardiographic, Biochemical, and Histopathological Approach

Retraction Note: Indoleamine 2,3-Dioxygenase 1 (IDO1) Promotes Cardiac Hypertrophy via a PI3K-AKT-mTOR-Dependent Mechanism

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page