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. 2021 Sep 22:12:690619.
doi: 10.3389/fphys.2021.690619. eCollection 2021.

Protective Role of Vitamin B1 in Doxorubicin-Induced Cardiotoxicity in Rats: Focus on Hemodynamic, Redox, and Apoptotic Markers in Heart

Marina Rankovic  1 , Nevena Draginic  1   2 , Jovana Jeremic  1 , Andjela Milojevic Samanovic  3 , Svetlana Stojkov  4 , Slobodanka Mitrovic  5 , Nevena Jeremic  1 , Tanja Radonjic  6 , Ivan Srejovic  7   8 , Sergey Bolevich  2 , Andrey Svistunov  9 , Vladimir Jakovljevic  2   7 , Tamara Nikolic Turnic  1
Affiliations

Protective Role of Vitamin B1 in Doxorubicin-Induced Cardiotoxicity in Rats: Focus on Hemodynamic, Redox, and Apoptotic Markers in Heart

Marina Rankovic et al. Front Physiol. .

Abstract

Up until now, the specific mechanisms involved in doxorubicin (DOX)-induced cardiotoxicity have not been fully elucidated. Since thiamine deficiency is associated with myocardial dysfunction and it may lead to cardiomyopathy, we aimed to investigate whether thiamine (Vitamin B1) treatment provides cardioprotection and modulates DOX mediated subchronic cardiotoxicity as well as to determine possible mechanisms of its effects. The study involved 48 Wistar albino rats divided into four groups: healthy non-treated rats and healthy rats treated with thiamine and DOX rats without treatment and DOX rats treated with thiamine. DOX was applied as a single i.p.injection (15mg/kg), while thiamine treatment lasted 7days (25mg/kg/dayi.p.). Before and after the treatment hemodynamic changes were monitored in vivo by echocardiography. When the protocol was completed, animals were sacrificed and rat hearts were isolated in order to evaluate parameters of cardiac oxidative stress [superoxide anion radical-O2 -, hydrogen peroxide-H2O2, nitric oxide-NO-, index of lipid peroxidation-thiobarbituric acid (TBA) reactive substances (TBARS), superoxide dismutase - SOD, catalase (CAT), and reduced glutathione-GSH] and apoptosis (Bax, Bcl-2, caspases). DOX treatment significantly reduced the ejection fraction, while thiamine treatment led to its minor increase in the DOX-treated group. In that sense, heart oxidative stress markers were significantly increased in DOX-treated rats, while therapeutic dose of thiamine decreased the levels of free radicals. Our study demonstrated the promising ameliorative effects of thiamine against DOX-induced cardiotoxicity through modulation of oxidative stress, suppression of apoptosis, and possibility to improve myocardial performance and morphometric structure of rats` hearts.

Keywords: apoptosis; cardiotoxicity; doxorubicin; heart oxidative stress; left ventricular function; rat; thiamine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Changes in the heart tissue pro-oxidative parameters of O2− (A), hydrogen peroxide (H2O2; B), nitrites (NO2−; C), and thiobarbituric acid (TBA) reactive substances (TBARS; D) in the control (CTRL), thiamine intraperitoneally (THIA), doxorubicin (DOX), and DOX+THIA groups. Values are presented as means±SEM. a p<0.05 compared with the normal CTRL group; b p<0.05 compared with the THIA group; c p<0.05 compared with the DOX group; and d p<0.05 compared with the DOX+THIA group.
Figure 2
Figure 2
Changes in the heart tissue antioxidative parameters of superoxide dismutase (SOD; A), catalase (CAT; B), and glutathione (GSH; C) in the CTRL, THIA, DOX, and DOX+THIA groups. Values are presented as means±SEM. a p<0.05 compared with the normal CTRL group; b p<0.05 compared with the THIA group; c p<0.05 compared with the DOX group; and d p<0.05 compared with the DOX+THIA group.
Figure 3
Figure 3
Representative heart tissue sections of hematoxylin/eosin-staining. White arrows indicate representative changes in the heart tissue. (A) CTRL, (B) THIA, (C) DOX, and (D) DOX+THIA. Original magnification 20×.
Figure 4
Figure 4
Representative heart tissue sections of immunohistochemical staining of Bax. (A) CTRL, (B) THIA, (C) DOX, and (D) DOX+THIA. Original magnification 20×.
Figure 5
Figure 5
Representative heart tissue sections of immunohistochemical staining of Caspase-3. (A) CTRL, (B) THIA, (C) DOX, and (D) DOX+THIA. Original magnification 20×.
Figure 6
Figure 6
Representative heart tissue sections of immunohistochemical staining of Bcl-2. (A) CTRL, (B) THIA, (C) DOX, and (D) DOX+THIA. Original magnification 20×.
Figure 7
Figure 7
Representative heart tissue sections of immunohistochemical staining of heat shock protein 70. (A) CTRL, (B) THIA, (C) DOX, and (D) DOX+THIA. Original magnification 20×.
Figure 8
Figure 8
cTnT-immunostaining. (A) CTRL, (B) THIA, (C) DOX, and (D) DOX+THIA. Original magnification 20×.
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References

    1. Abdel-Daim M. M., Kilany O. E., Khalifa H. A., Ahmed A. A. M. (2017). Allicin ameliorates doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Cancer Chemother. Pharmacol. 80, 745–753. doi: 10.1007/s00280-017-3413-7, PMID: - DOI - PubMed
    1. Argun M., Üzüm K., Sönmez M. F., Özyurt A., Derya K., Çilenk K. T., et al. . (2016). Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats. Anatol. J. Cardiol. 16, 234–241. doi: 10.5152/akd.2015.6185, PMID: - DOI - PMC - PubMed
    1. Atar S., Ye Y., Lin Y., Freeberg S. Y., Nishi S. P., Rosanio S., et al. . (2006). Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2. Am. J. Physiol. Heart Circ. Physiol. 290, H1960–H1968. doi: 10.1152/ajpheart.01137.2005, PMID: - DOI - PubMed
    1. Auclair C., Voisin E. (1985). “Nitroblue tetrazolium reduction,” in Handbook of Methods for Oxygen Radical Research. ed. Greenvvald R. A. (Boca Raton: CRC Press, Une; ), 123–132.
    1. Bertinchant J. P., Polge A., Juan J. M., Oliva-Lauraire M. C., Giuliani I., Marty-Double C., et al. . (2003). Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings. Clin. Chim. Acta 329, 39–51. doi: 10.1016/S0009-8981(03)00013-5, PMID: - DOI - PubMed