In vivo evaluation of the protective effects of arjunolic acid against lipopolysaccharide-induced septic myocardial injury

Hany Elsawy; Mohammed Almalki; Omar Elmenshawy; Ashraf Abdel-Moneim

doi:10.7717/peerj.12986

In vivo evaluation of the protective effects of arjunolic acid against lipopolysaccharide-induced septic myocardial injury

PeerJ. 2022 Feb 16:10:e12986. doi: 10.7717/peerj.12986. eCollection 2022.

Authors

Hany Elsawy^{1

2}, Mohammed Almalki³, Omar Elmenshawy^{3

4}, Ashraf Abdel-Moneim^{3

5}

Affiliations

¹ Department of Chemistry, Faculty of Science, King Faisal University, Al-Ahsa, Saudi Arabia.
² Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
³ Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa, Saudi Arabia.
⁴ Department of Zoology, Faculty of Science, Al Azhar University, Cairo, Egypt.
⁵ Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt.

Abstract

Lipopolysaccharide (LPS) is a glycolipid component of the cell wall of Gram-negative bacteria, which induces multiple organ dysfunctions, eventually leading to septic shock and death. Arjunolic acid (AA) has been shown to have therapeutic benefits against various organ pathophysiologies, although its role in sepsis remains unclear. Here, we evaluated the effects of AA on LPS-induced free radical production and cardiotoxicity. Male albino mice were allocated to four groups: normal, 1.5 µg/30 g b.w. of LPS (LPS), 20 mg/kg b.w. AA with LPS (AA+LPS) and 20 mg/kg b.w. of AA (AA). Subsequently, blood and heart samples were harvested for biochemical and histopathological examinations. Pretreatment with AA attenuated LPS-induced increased serum levels of cardiac troponin I, lactate dehydrogenase and creatine kinase. In the meantime, AA pretreatment before LPS resulted in a significant increase in endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione) and a significant decrease in the level of lipid peroxidation product (malondialdehyde) in the heart as compared to the LPS group, while cardiac cytochrome c activity were significantly increased. In addition, in the AA-pretreated mice, C-reactive protein and proinflammatory cytokines (interlukin-1 and tumor necrosis factor-alpha) were significantly reduced, and anti-inflammatory cytokines (interleukin-4 and -10) were significantly increased in cardiac tissues as compared to the LPS-treated animals. Furthermore, prior administration of AA to LPS exposed mice led to a significant a significant decrease in heart caspase-3, -8, and -9 as compared to the LPS group. Interestingly, AA was also able to improve LPS-induced histopathological changes in the cardiomyocytes. In conclusion, these in vivo findings indicate that AA may be a promising cardioprotective agent against LPS-stimulated cardiotoxicity, at least in part, through upregulation of cardiac antioxidants, reduction of lipid peroxidation, and inhibition of inflammation and cardiac cell death.

Keywords: Arjunolic acid; Cardiotoxicity; Caspase-3/8/9; Cytokines; Endotoxin; Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / pharmacology
Cardiotoxicity / drug therapy
Cytokines / metabolism
Heart Injuries* / metabolism
Lipopolysaccharides* / toxicity
Male
Mice
Myocytes, Cardiac / metabolism
Oxidative Stress

Substances

Lipopolysaccharides
arjunolic acid
Antioxidants
Cytokines

Grants and funding

This work was financially supported by the Deanship of Scientific Research at King Faisal University (Saudi Arabia) under grant no. 170056. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.