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The Effects of Levosimendan Against Sepsis-Induced Cardiotoxicity in Mice Model

Journal: Journal of Medicinal and Chemical Sciences (Vol.6, No. 3)

Publication Date:

Authors : ; ; ; ;

Page : 634-644

Keywords : CLP; Polymicrobial sepsis; cardiotoxicity; cardiac troponin; Oxidative pathway;

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Abstract

Sepsis is an upregulated systemic inflammatory reaction that has been identified as a global health concern. It can lead to multiple organ toxicity, including cardiac, hepatic, and renal dysfunction. Sepsis can result in cardiomyocyte impairment, hypertrophy, and heart failure by increasing oxidative stress and the expression of pro-inflammatory cytokines. Furthermore, elevated cardiac troponin-I (cTn-I) during sepsis impairs heart contractile performance by decreasing myofilament response to calcium. The current study aimed to examine the possible effects of levosimendan against sepsis-induced cardiotoxicity. Forty male mice 8-12 weeks old and weighing 25-30 grams. After two weeks of acclimation, the mice were separated into four groups (n = 10): (1) Healthy group (n = 10). (2) CLP group: CLP operation was performed on mice. (3) DMSO group (4) Levosimendan group: 10 mg/kg intraperitoneally (IP) in 2 divided doses for 5 consecutive days. All groups underwent the CLP procedure on the fourth day, were sacrificed on the fifth day, and then samples were taken. The Levosimendan group exhibited a significant (p < 0.05) decrease in myocardial troponin-I concentration compared to the CLP group. In addition, the inflammatory cytokines (TNF-α, IL-6, and IL-1β) serum levels in the levosimendan group were significantly (p < 0.05) lower than in the CLP group. In addition, the levosimendan group demonstrated a significant (p0.05) increase in myocardial SOD activity and a decrease in MDA level compared to the CLP mice. Histopathologically, the levosimendan group demonstrated a statistically significant (p0.05) reduction in cardiac tissue damage. Levosimendan attenuates sepsis-induced cardiotoxicity via multiple protective effects, including anti-inflammatory and antioxidant effects, according to the findings of the present study. In addition, the direct cardiac protective effect via the decreased cardiac troponin-I level and the attenuation of histopathological alterations during sepsis-induced cardiotoxicity.

Last modified: 2022-10-09 03:08:00