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Article

Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats

by
Carolina R. Tonon
1,*,
Marina G. Monte
1,
Paola S. Balin
1,
Anderson S. S. Fujimori
1,
Ana Paula D. Ribeiro
1,
Natália F. Ferreira
1,
Nayane M. Vieira
1,
Ronny P. Cabral
1,
Marina P. Okoshi
1,
Katashi Okoshi
1,
Leonardo A. M. Zornoff
1,
Marcos F. Minicucci
1,
Sergio A. R. Paiva
1,
Mariana J. Gomes
2 and
Bertha F. Polegato
1
1
Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil
2
Department of Kinesiology and Sport Management, Texas A&M University, College Station, TX 77843, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(11), 5833; https://doi.org/10.3390/ijms25115833
Submission received: 15 March 2024 / Revised: 17 May 2024 / Accepted: 20 May 2024 / Published: 27 May 2024
(This article belongs to the Special Issue Heart Failure Mechanisms and Treatment Advances)
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Abstract

Doxorubicin is an effective drug for cancer treatment; however, cardiotoxicity limits its use. Cardiotoxicity pathophysiology is multifactorial. GLP-1 analogues have been shown to reduce oxidative stress and inflammation. In this study, we evaluated the effect of pretreatment with liraglutide on doxorubicin-induced acute cardiotoxicity. A total of 60 male Wistar rats were allocated into four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). L and DL received subcutaneous injection of liraglutide 0.6 mg/kg daily, while C and D received saline for 2 weeks. Afterwards, D and DL received a single intraperitoneal injection of doxorubicin 20 mg/kg; C and L received an injection of saline. Forty-eight hours after doxorubicin administration, the rats were subjected to echocardiogram, isolated heart functional study, and euthanasia. Liraglutide-treated rats ingested significantly less food and gained less body weight than animals that did not receive the drug. Rats lost weight after doxorubicin injection. At echocardiogram and isolated heart study, doxorubicin-treated rats had systolic and diastolic function impairment. Myocardial catalase activity was statistically higher in doxorubicin-treated rats. Myocardial protein expression of tumor necrosis factor alpha (TNF-α), phosphorylated nuclear factor-κB (p-NFκB), troponin T, and B-cell lymphoma 2 (Bcl-2) was significantly lower, and the total NFκB/p-NFκB ratio and TLR-4 higher in doxorubicin-treated rats. Myocardial expression of OPA-1, MFN-2, DRP-1, and topoisomerase 2β did not differ between groups (p > 0.05). In conclusion, doxorubicin-induced cardiotoxicity is accompanied by decreased Bcl-2 and phosphorylated NFκB and increased catalase activity and TLR-4 expression. Liraglutide failed to improve acute doxorubicin-induced cardiotoxicity in rats.
Keywords: doxorubicin; heart failure; acute cardiotoxicity doxorubicin; heart failure; acute cardiotoxicity

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MDPI and ACS Style

Tonon, C.R.; Monte, M.G.; Balin, P.S.; Fujimori, A.S.S.; Ribeiro, A.P.D.; Ferreira, N.F.; Vieira, N.M.; Cabral, R.P.; Okoshi, M.P.; Okoshi, K.; et al. Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats. Int. J. Mol. Sci. 2024, 25, 5833. https://doi.org/10.3390/ijms25115833

AMA Style

Tonon CR, Monte MG, Balin PS, Fujimori ASS, Ribeiro APD, Ferreira NF, Vieira NM, Cabral RP, Okoshi MP, Okoshi K, et al. Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats. International Journal of Molecular Sciences. 2024; 25(11):5833. https://doi.org/10.3390/ijms25115833

Chicago/Turabian Style

Tonon, Carolina R., Marina G. Monte, Paola S. Balin, Anderson S. S. Fujimori, Ana Paula D. Ribeiro, Natália F. Ferreira, Nayane M. Vieira, Ronny P. Cabral, Marina P. Okoshi, Katashi Okoshi, and et al. 2024. "Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats" International Journal of Molecular Sciences 25, no. 11: 5833. https://doi.org/10.3390/ijms25115833

APA Style

Tonon, C. R., Monte, M. G., Balin, P. S., Fujimori, A. S. S., Ribeiro, A. P. D., Ferreira, N. F., Vieira, N. M., Cabral, R. P., Okoshi, M. P., Okoshi, K., Zornoff, L. A. M., Minicucci, M. F., Paiva, S. A. R., Gomes, M. J., & Polegato, B. F. (2024). Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats. International Journal of Molecular Sciences, 25(11), 5833. https://doi.org/10.3390/ijms25115833

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