Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Koom, Egypt.
Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
J Biochem Mol Toxicol. 2024 Aug;38(8):e23804. doi: 10.1002/jbt.23804.
The present study evaluated the cardioprotective effect of astaxanthin (ASX) against isoproterenol (ISO) induced myocardial infarction in rats via the pathway of mitochondrial biogenesis as the possible molecular target of astaxanthin. The control group was injected with normal physiological saline subcutaneously for 2 days. The second group was injected with ISO at a dose of 85 mg/kg bwt subcutaneously for 2 days. The third, fourth and fifth groups were supplemented with ASX at doses of 10, 20, 30 mg/kg bwt, respectively daily by oral gavage for 21 days then injected with ISO dose of 85 mg/kg bwt subcutaneously for 2 successive days. Isoproterenol administration in rats elevated the activities of Creatine kinase-MB (CK-MB), aspartate transaminase (AST), lactate dehydrogenase (LDH), and other serum cardiac biomarkers Troponin-I activities, oxidative stress biomarkers, malondialdehyde(MDA), Nuclear factor-kappa B (NF-KB), while it decreased Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), Nuclear factor erythroid-2-related factor 2 (Nfe212), mitochondrial transcriptional factor A (mt TFA), mitochondrial DNA copy number and glutathione system parameters. However, Astaxanthin decreased the activities of serum AST, LDH, CK-MB, and Troponin I that elevated by ISO. In addition, it increased glutathione peroxidase and reductase activities, total glutathione and reduced GSH content, and GSH/GSSG ratio, mtDNA copy number, PGC-1α expression and Tfam expression that improved mitochondrial biogenesis while it decreased GSSG and MDA contents and NF-KB level in the cardiac tissues. This study indicated that astaxanthin relieved isoproterenol induced myocardial infarction via scavenging free radicals and reducing oxidative damage and apoptosis in cardiac tissue.
本研究通过可能的分子靶点——线粒体生物发生途径,评估虾青素(ASX)对异丙肾上腺素(ISO)诱导的大鼠心肌梗死的心脏保护作用。对照组皮下注射生理盐水 2 天。第二组皮下注射 ISO 剂量为 85mg/kg bwt,连续 2 天。第三、四、五组分别每天口服补充 ASX 剂量为 10、20、30mg/kg bwt,连续 21 天,然后皮下注射 ISO 剂量为 85mg/kg bwt,连续 2 天。ISO 给药可升高肌酸激酶同工酶-MB(CK-MB)、天门冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)和其他血清心脏生物标志物肌钙蛋白 I 活性,同时还可升高氧化应激生物标志物丙二醛(MDA)、核因子-κB(NF-KB)的活性,降低过氧化物酶体增殖物激活受体-γ共激活因子(PGC-1α)、核因子红细胞 2 相关因子 2(Nfe212)、线粒体转录因子 A(mt TFA)、线粒体 DNA 拷贝数和谷胱甘肽系统参数。然而,虾青素可降低 ISO 升高的血清 AST、LDH、CK-MB 和肌钙蛋白 I 的活性。此外,它可增加谷胱甘肽过氧化物酶和还原酶活性、总谷胱甘肽和还原型 GSH 含量、GSH/GSSG 比值、mtDNA 拷贝数、PGC-1α 表达和 Tfam 表达,从而改善线粒体生物发生,同时降低心脏组织中 GSSG 和 MDA 含量以及 NF-KB 水平。本研究表明,虾青素通过清除自由基和减少心脏组织中的氧化损伤和细胞凋亡来缓解 ISO 诱导的心肌梗死。