Department of Chemistry, Faculty of Science, King Faisal University, Al-Ahsa, Saudi Arabia.
Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
PeerJ. 2022 Feb 16;10:e12986. doi: 10.7717/peerj.12986. eCollection 2022.
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 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.
脂多糖（LPS）是革兰氏阴性菌细胞壁的糖脂成分，可诱导多器官功能障碍，最终导致感染性休克和死亡。已证明阿魏酸（AA）对各种器官病理生理具有治疗益处，尽管其在败血症中的作用尚不清楚。在这里，我们评估了 AA 对 LPS 诱导的自由基产生和心脏毒性的影响。雄性白化小鼠分为四组：正常组、1.5μg/30g.b.w.LPS（LPS）组、20mg/kg.b.w.AA+LPS（AA+LPS）组和 20mg/kg.b.w.AA（AA）组。随后采集血液和心脏样本进行生化和组织病理学检查。AA 预处理可减轻 LPS 诱导的血清心肌肌钙蛋白 I、乳酸脱氢酶和肌酸激酶水平升高。同时，与 LPS 组相比，AA 预处理后 LPS 导致心脏内源性抗氧化剂（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和还原型谷胱甘肽）显著增加，脂质过氧化产物（丙二醛）水平显著降低，而心脏细胞色素 c 活性显著增加。此外，在 AA 预处理的小鼠中，与 LPS 处理的动物相比，心脏组织中的 C 反应蛋白和促炎细胞因子（白细胞介素-1 和肿瘤坏死因子-α）显著减少，抗炎细胞因子（白细胞介素-4 和白细胞介素-10）显著增加。此外，与 LPS 组相比，AA 预先给予 LPS 暴露的小鼠可导致心脏 caspase-3、-8 和 -9 显著减少。有趣的是，AA 还能够改善 LPS 诱导的心肌细胞的组织病理学变化。总之，这些发现表明 AA 可能是一种有前途的心肌保护剂，可对抗 LPS 刺激的心肌毒性，至少部分是通过上调心脏抗氧化剂、减少脂质过氧化以及抑制炎症和心肌细胞死亡。
