• Journal of Chest Surgery
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• v.54 no.1
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• pp.9-16
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• 2021

Background: The deposition of monomeric C-reactive protein (mCRP) in the myocardium aggravates ischemia-reperfusion injury (IRI) and myocardial infarction. Ischemic preconditioning (IPC) is known to protect the myocardium against IRI. Methods: We evaluated the effects of IPC on myocardium upon which mCRP had been deposited due to IRI in a rat model. Myocardial IRI was induced via ligation of the coronary artery. Direct IPC was applied prior to IRI using multiple short direct occlusions of the coronary artery. CRP was infused intravenously after IRI. The study included sham (n=3), IRI-only (n=5), IRI+CRP (n=9), and IPC+IRI+CRP (n=6) groups. The infarcted area and the area at risk were assessed using Evans blue and 2,3,5-triphenyltetrazolium staining. Additionally, mCRP immunostaining and interleukin-6 (IL-6) mRNA reverse transcription-polymerase chain reaction were performed. Results: In the IRI+CRP group, the infarcted area and the area of mCRP deposition were greater, and the level of IL-6 mRNA expression was higher, than in the IRI-only group. However, in the IPC+IRI+CRP group relative to the IRI+CRP group, the relative areas of infarction (20% vs. 34%, respectively; p=0.079) and mCRP myocardial deposition (21% vs. 44%, respectively; p=0.026) were lower and IL-6 mRNA expression was higher (fold change: 407 vs. 326, respectively; p=0.376), although the difference in IL-6 mRNA expression was not statistically significant. Conclusion: IPC was associated with significantly decreased deposition of mCRP and with increased expression of IL-6 in myocardium damaged by IRI. The net cardioprotective effect of decreased mCRP deposition and increased IL-6 levels should be clarified in a further study.

• Journal of Chest Surgery
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• v.56 no.5
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• pp.295-303
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• 2023

Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups: a control group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor (TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV) tissues from each group. Results: Losartan administration reduced LV hypertrophy, collagen content, and the expression of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment induced a reduction in the apoptotic area compared to group A. Conclusion: In an ADR-induced cardiomyopathy rat model, co-administration of ADR with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory factors, and apoptosis in LV tissue.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.145-152
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• 2017

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (non-cardiac) increases the tolerance of the myocardium to sustained ischemia-reperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

• Bulletin of the Korean Chemical Society
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• v.25 no.2
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• pp.207-212
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• 2004

In this study, we attempted to prepare compounds with heterocyclic replacements for metabolically unstable esters of benzopyranyl indole-2-carboxylic esters, which showed good in vitro and in vivo cardioprotective efficacies possibly through the opening of mitochondrial ATP-sensitive potassium channel ($K_{ATP}$). Initially, we tried to construct indolin-2-yl-heterocycles using unprotected indoline-2-carboxylic acid, but the cyclization was proceeded with oxidation of the indoline ring to the indole, which didn't react with benzopyranyl epoxide. Thus we introduced N-Boc group to deplete the electron density of the indoline ring. We successfully prepared various indolin-2-yl-heterocycles by the cyclization of the building blocks including carboxamide, ${\beta}$-hydroxy amide, hydrazide, nitrile starting from N-Boc-indoline-2-carboxylic acid.

• Journal of Nutrition and Health
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• v.33 no.7
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• pp.739-744
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• 2000

The purpose of this study was to elucidate protective effect of Fructus Schsandrae(FS) water extract against xanthine oxidase/hypoxanthine(XO/HX)-induced cardiotoxicity in myocardial cells this experiment was performed. Cardiotoxicity of XO/HX was examined by MTT(MTT [3-(4,5-dimethylthiazol-2-yl)-2.5,-diphenyl tetrazolium bromide) assay. XO/HX induced the decrease of cell viability. Also XO/HX induced the increase of LDH activity and the decrease of beating rate on cultured myocardial cells in a dose-dependent manner. To investigate cardioprotective effect of FS water extract cultures were preincubated with FS water extract for 3 hours. Cultures were then exposed to XO/HX for 72 hours. FS water extract have an efficacy in decreaasing LDH activity and increasing heart beating rate on cultured myocardial cells damaged by XO/HX. From the results it is suggested that XO/HX may show toxic effect in cultured myocardial cells derived from neonatal mouse and FS water extract is effective in the prevention of XO/HX-induced cardiotoxicity.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.462-465
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• 2016

In the present study, we investigated whether treatment with GBCK25 facilitated the recovery of hemodynamic parameters, left ventricle systolic pressure, left ventricular developed pressure, and electrocardiographic changes. GBCK25 significantly prevented the decrease in hemodynamic parameters and ameliorated the electrocardiographic abnormality. These results indicate that GBCK25 has distinct cardioprotective effects in rat heart.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.143.1-143.1
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• 2003

In this study. we investigated whether the cardioprotective effect shown by quercetin 3-O-$\alpha$-arabinofuranoside extracted from Lindera erythrocarpa against ROS-induced cell death in H9c2 cardiac myocytes. Cell death was induced by BSO, buthionine sulfoximine, which inhibits GSH level and subsequntly increase ROS level. Cell death was quntitatively determined by measuring lactate dehydrogenase (LDH) activity. (omitted)

• Archives of Pharmacal Research
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• v.28 no.11
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• pp.1287-1292
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• 2005

KR-33028 (N-[4-cyano-benzo[b]thiophene-2-carbonyl]guanidine) is a new cardioprotective agent for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-33028 in human liver microsomes and to compare its metabolism with that of cryopreserved human hepatocytes. Human liver microsomal incubation of KR-33028 in the presence of NADPH and UDPGA resulted in the formation of four metabolites, M1, M2, M3, and M4. M1 and M2 were identified as 5-hydroxy-KR-33028 and 7-hydroxy-KR-33028, respectively, on the basis of LC/MS/MS analysis with the synthesized authentic standard. M3 and M4 were suggested to be dihydroxy-KR-33028 and hydroxy-KR-33028-glucuronide, respectively. Metabolism of KR-33028 in cryopreserved human hepatocytes resulted in the formation of M1, M2, and M4. These data show a good correlation between major metabolites formed in human liver microsomes and cryopreserved human hepatocytes. In addition, KR­33028 was found to inhibit moderately the metabolism of CYP1A2 substrates. Based on the results obtained metabolic pathway of KR-33028 is proposed.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.642-653
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• 2021

Background: Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury, and their crosstalk within I/R injury and in GP-17einduced cardioprotection are also explored. Methods: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactive oxygen species production, and respiratory function were determined using fluorescence detection kits on mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. Results: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. Conclusion: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.136-139
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• 2003

Cytotoxicity of glucose oxidase(GO) and cardioprotective effect of Salviae Multiorrhizae Radix(SMR) against GO-induced cardiotoxicity were measured for evaluation of cardiotoxicity on cultured mouse pulmonary endotherial cells(PEC) by MTT assay after PEC were cultured for 8 hours at various concentrations of GO. GO was toxic in a time and dose-dependent manner on cultured PEC after PEC were grown for 8 hours in media containing 1～60mU/ml GO. While, cultures were pretreated with 60 μg/ml SMR for 2 hours increased remarkably cell viability. From the above results, it is suggested that GO is toxic on cultured PEC by the decrease of cell viability, and herb medicine such as SMR is very effective in the prevention of vascular toxicity induced by GO.