• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.85-85
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• 2004

• 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.

• Nanomaterials
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• v.9 no.12
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• pp.1652-1663
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• 2019

Osteosarcoma (OSA) is a difficult cancer to treat due to its tendency for relapse and metastasis; advanced methods are therefore required for OSA treatment. In this study, we prepared a local drug-delivery system for OSA treatment based on doxorubicin·hydrochloride (DOX·HCl)/cisplatin (CP)-loaded visible light-cured glycol chitosan (GC) hydrogel/(2-hydroxypropyl)-beta-cyclodextrin (GDHCP), and compared its therapeutic efficiency with that of DOX·HCl- and CP-loaded GC hydrogels (GD and GHCP). Because of diffusion driven by concentration gradients in the swollen matrix, the three hydrogels showed sustained releases of DOX·HCl and CP over 7 days, along with initial 3-h bursts. Results of in vitro cell viability and in vivo animal testing revealed that GDHCP had a stronger anticancer effect than GD and GHCP even though there were no significant differences. Body weight measurement and histological evaluations demonstrated that the drug-loaded GC hydrogels had biocompatibility without cardiotoxicity or nephrotoxicity. These results suggested that GDHCP could be a good platform as a local drug-delivery system for clinical use in OSA treatment.

• Clinical and Experimental Pediatrics
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• v.50 no.8
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• pp.774-780
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• 2007

Purpose : The anthracyclines (AC) are widely used chemotherapeutic agents for pediatric cancers. However, the therapeutic use of these agents is limited by their cardiotoxicity. The aim of the present study was to investigate the usefulness of plasma B-type natriuretic peptide (BNP) levels as a marker for AC-induced cardiotoxicity compared to echocardiography in Korean children with cancer. Methods : Fifty-five pediatric cancer patients who had received chemotherapy including AC were enrolled. The cumulative AC doses, clinical symptoms, and two echocardiography parameters, left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF), were studied and compared with plasma BNP levels. Results : In 55 patients, plasma BNP levels were measured 115 times and echocardiographies were performed 64 times. The median cumulative dose of AC was $325mg/m^2$ (range 120-600; mean 345) and the median plasma BNP level was 10 pg/mL (range 5-950; mean 31). The cumulative AC doses correlated significantly with the plasma BNP levels (P=0.002). The plasma BNP levels correlated significantly with LVFS (P=0.018) and LVEF (P=0.025). Dilated cardiomyopathies were identified in three patients. LVFS and LVEF decreased and plasma BNP levels increased in a patient with acute dilated cardiomyopathy and in that with symptomatic chronic dilated cardiomyopathy. However, LVFS, LVEF and plasma BNP levels were normal in a patient with asymptomatic chronic dilated cardiomyopathy. Conclusion : The results of this study demonstrated that plasma BNP levels could be used as a marker for AC-induced cardiotoxicity; they showed good correlation with echocardiography findings in pediatric cancer patients. Plasma BNP levels may be used for the detection and management of AC-induced cardiotoxicity in Korean children with cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2301-2305
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• 2016

Background: The early detection of anthracycline- induced cardiotoxicity is very important since it might be useful in prevention of cardiac decompensation. This study was designed with the intent of assessing the usefulness of cardiac troponin T (cTnT) and NT- Pro BNP estimation in early prediction of anthracycline induced cardiotoxicity. Materials and Methods: In this prospective study histologically proven breast cancer patients who were scheduled to receive anthracycline containing combination chemotherapy as a part of multimodality treatment were enrolled. Baseline cardiac evaluation was performed by echocardiography (ECHO) and biomarkers like cardiac troponin T (cTnT) and N terminal- pro brain natriuretic peptide (NT- Pro BNP). All patients underwent cTnT and NT- Pro BNP estimation within 24 hours of each cycle of chemotherapy and were followed up after 6 months of initiation of chemotherapy. Any changes in follow up ECHO were compared to ECHO at baseline and cTnT and NT- Pro BNP levels after each cycle of anthracycline-based chemotherapy. Results: Initial data were obtained for 33 patients. Mean change in left ventricular diastolic diameter (LVDD) within 6 months was $0.154{\pm}0.433cms$ (p value=0.049). Seven out of 33 patients had an increase in biomarker cTnT levels (p value=0.5). A significant change in baseline and follow up LVDD was observed in patients with raised cTnT levels (p value=0.026) whereas no change was seen in ejection fraction (EF) and left atrial diameters (LAD) within 6 months of chemotherapy. NT- Pro BNP levels increased in significant number of patients (p value ${\leq}0.0001$) but no statistically significant change was observed in the ECHO parameters within 6 months. Conclusions: Functional monitoring is a poorly effective method in early estimation of anthracycline induced cardiac dysfunction. Estimation of biomarkers after chemotherapy may allow stratification of patients in various risk groups, thereby opening window for interventional strategies in order to prevent permanent damage to the myocardium.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.955-959
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• 2002

To test the protective effect of herbal medicine on myocardial damage against oxygen free radical-induced myocardiotoxicity, cytotoxicity was examined using MTT, Beating rate and TSARS assay in the presence of water extract of Rhizoma Coptidis. Myocardial toxicity was evaluated in neonatal rat myocardiocytes in cultures. The results of these experiments were obtained as follows: Xanthine oxydase/hypoxanthine resulted in a decrease in viability, beating rate and in a increase in lipid peroxidation in Cultured myocardial cells. Rhizoma Coptidis water extract shows effects of protection from the cardiocyte toxicity induced by xanthine oxydase/hypoxanthine treatment such as increases in beating rate. Rhizoma Coptidis water extract shows effects of protection from the cardiocyte toxicity induced by xanthine oxydase/hypoxanthine treatment such as decreases in lipid peroxidation. These results show that xanthine oxydase/hypoxanthine elicits toxic effects. in cultured myocardial cells derived from neonatal rat, and suggest that water extract of Rhizoma Coptidis is very effective in the prevention of xanthine oxydase/hypoxanthine-induced cardiotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5785-5790
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• 2012

The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.353-358
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• 2002

To test the protective effect of herbal medicine against oxygen free radical-induced myocardiotoxicity, cytotoxicity of xanthine oxidase/hypoxanthine (XO/HX) was examined using MTT, TBARS, and beating rate assay in the presence of water extract of Sujeom-san(SJS) or single consituents of its prescription. Myocardial toxicity was evaluated in neonatal rat myocardiocytes in cultures. In the present paper, XO/HX resulted in a decrease in viability and beating rate and increases in lipid peroxidation in cultured myocardial cells. In the effect of SJS water extract, it showed effects from the cardiocytotoxicity induced by XO/HX treatment such as increases in beating rate and decreases in lipid peroxidation. In the effect of Rhizoma Corydalis (RC), Faeces Trogopterori (FT), Fructus Amomi Tsaoko (FAT) and Myrrha on the cardiocytotoxicity, they were significantly effective in blocking the XO/HX-induced cardiocytotoxicity by increase of beating rate in FAT and FT group as well as decrease of lipid peroxidation in FT and RC group. These results show that oxygen free radical elicits toxic effects in cultured myocardial cells derived from neonatal rat, and suggest that water extract of Sujeomsan, Rhizoma Corydalis, Faeces Trogopterori, Fructus Amomi Tsaoko or Myrrha is very effective in the prevention of xanthine oxidase/hypoxanthine- induced cardiotoxicity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1117-1121
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• 2002

To test the protective effect of herbal medicine on myocardial damage against oxygen free radical-induced myocardiotoxicity, cytotoxicity was examined using MTT, Beating rate and DNA synthesis assay in the presence of water extract of three kinds of Radix Rehmanniae. Myocardial toxicity was evaluated in neonatal rat myocardiocytes in cultures. The results of these experiments were obtained as follows : Xanthine oxydase/hypoxanthine resulted in a decrease in viability, beating rate and DNA synthesis in cultured myocardial cells. Radix Rehmanniae Recens(生地黃, RRR) water extract shows effects of protection from the cardiocyte toxicity induced by xanthine oxydase/hypoxanthine treatment such as increases in beating rate. Radix Rehmanniae Preparat(熟地黃, RRP) water extract shows effects of protection from the cardiocyte toxicity induced by xanthine oxydase/hypoxanthine treatment such as increases in DNA synthesis. These results show that xanthine oxydase/hypoxanthine elicits toxic effects in cultured myocardial cells derived from neonatal rat, and suggest that water extract of three kinds of Radix Rehmanniae is very effective in the prevention of xanthine oxydase/hypoxanthine-induced cardiotoxicity.

• Applied Microscopy
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• v.19 no.2
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• pp.99-118
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• 1989

The cardiotoxic effects of acute and chronic administration of adriamycin (ADR) were evaluated in A/J Swiss albino mice. In acute studies, male mice received intravenous ADR, 5mg or 15mg/kg per day for 3 or 1day and were sacrifice 12 hours later. Because the glutathione-glutathione peroxidase system is major pathway for free radical detoxication, glutathione levels and glutathione peroxidase activity was measured. In acute studies, ADR-treated mice exhibited significantly decreased levels(p<0.05) of total glutathione and unchanged levels of oxidized glutathione and percentage of oxidized glutathione. The earliest myocardial fine structural alterations included swelling and degeneration of mitochondria and dilatation of sarcoplasmic reticulum at all dosage of acute models. In chronic studies, mice received 5mg/kg ADR once a week for up to 16 weeks. Levels of total and reduced glutathione were decreased significantly(p<0.01) and oxidized glutathione and percentage of oxidized glutathione were increased significantly (p<0.05). Chronic myocardial lesions included perinuclear vacuolization, seperation of myofibrils and the fasciae adherens of intercalated disc and hypercontraction band within myocyte. Glutathione peroxidase activity reduced significantly (p<0.01) in any group of acute and chronic ADR-treated animals. Test for lipid peroxidation(malondialdehyde) was increased significantly(P<0.01). Thus, we conclude 1) ADR significantly lowers glutathione levels in heart tissue, and 2) cellular damage progress produced by alteration of this system in mouse models of ADR cardiotoxicity. These results suggest that the glutathione-glutathione peroxidase system may be involved in the modulation of ADR-induced cardiotoxicity.