• 동의생리병리학회지
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• 제16권6호
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• pp.1197-1200
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• 2002

To examine the cardiotoxicity of glucose oxidase(GO) in cultured myocardial cells, cardiotoxicity was measured by MTT assay. Myocardial cells were treated with 1～50 mU/ml GO for 5 hours. The cardioprotective effect of Benincasae Semen(BS) was measured by MTT assay in these cultrures. Cell viability was significantly decreased in dose- and time-dependently after myocardial cells were exposed to 30mU/ml GO for 5 hours. In the cardioprotective effect of BS on the cardiotoxicity induced by GO, BS prevented the cardiotoxicity induced by GO in these cultures. From these results, it suggests that GO had cytotoxic effect in cultured myocardial cells and herb extract, BS showed protective effect on GO-induced cardiotoxicity.

• Physical Therapy Rehabilitation Science
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• 제3권2호
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• pp.107-111
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• 2014

Objective: In the present study, we investigated the protective effects of low-intensity treadmill training in doxorubicin-induced cardiotoxicity rat models. Design: Randomized controlled trial. Methods: In this study, we randomly divided them into four groups. The normal group included non-cardiotoxicity normal control (n=10), the control group included non-treadmill training after doxorubicin-induced cardiotoxicity (n=10), the experimental group I included low-intensity treadmill training (3 m/min) after doxorubicin-induced cardiotoxicity (n=10), and the experimental group II included low-intensity treadmill training (8 m/min) after doxorubicin-induced cardiotoxicity (n=10). Rats in the treadmill training group underwent treadmill training, which began at 2 weeks after first intraperitoneal injection. We determined the body weight change for each rat on days 1 and 21. Biochemical markers (lactate dehydrogenase [LDH], creatine kinase [CK], glutathion, aspartate transaminase [AST], and alanine transaminase [ALT]) concentration in the serum change of rats from all four groups was examined at the end of the experiment. Results: The results showed that the experimental group I and II showed a significant increase in body weight as compared with that of the control group (p<0.05). We observed that the biochemical markers (LDH, CK, glutathion, AST, and ALT) were improved in the experimental group I than the experimental group II (p<0.05). There was no difference between the experimental groups. Conclusions: In conclusion, our data suggest that low-intensity treadmill training applied after doxorubicin treatment protects against cardiotoxicity following treatment, possibly by enhancing antioxidant defenses and inhibiting cardiac muscle cell apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.4045-4049
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• 2015

Objective: To investigate the effect of coenzyme complex on decreasing cardiotoxicity in elderly patients with gastrointestinal cancer who were treated by chemotherapy. Methods: From September 2011 to February 2015, we recruited 54 elderly (with more than 70 years of age) patients with gastrointestinal cancer, with advanced disease. Then treated with chemotherapy combined with or without coenzyme complex. After two cycles of treatment, the effect of coenzyme complex on decreasing cardiotoxicity were evaluated. Results: Chemotherapy was combined with coenzyme complex in 32 patients (22man, 10 woman; median age: 74 years, range: 70-87 years) without coenzyme complex in 22 patients (15man, 7 woman; median age: 73 years, range: 70-80 years) with gastrointestinal cancer. Cardiac event was significantly lower in patients treated with chemotherapy combined with coenzyme complex (p<0.01). Conclusions: Coenzyme Complex decreased cardiotoxicity when combined with chemotherapy in treating elderly patients with gastrointestinal cancer.

• 대한약침학회지
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• 제20권4호
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• pp.243-256
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• 2017

Doxorubicin as a chemotherapeutic drug is widely used for the treatment of patients with cancer. However, clinical use of this drug is hampered by its cardiotoxicity, which is manifested as electrocardiographic abnormalities, arrhythmias, irreversible degenerative cardiomyopathy and congestive heart failure. The precise mechanisms underlying the cardiotoxicity of doxorubicin are not clear, but impairment of calcium homeostasis, generation of iron complexes, production of oxygen radicals, mitochondrial dysfunction and cell membrane damage have been suggested as potential etiologic factors. Compounds that can neutralize the toxic effect of doxorubicin on cardiac cells without reducing the drug's antitumor activity are needed. In recent years, numerous studies have shown that herbal medicines and bioactive phytochemicals can serve as effective add-on therapies to reduce the cardiotoxic effects of doxorubicin. This review describes different phytochemicals and herbal products that have been shown to counterbalance doxorubicin-induced cardiotoxicity.

• Advances in Traditional Medicine
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• 제5권1호
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• pp.62-68
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• 2005

Doxorubicin is a powerful anticancer antibiotic extensively used in the treatment of several types of cancers. Long-term administration of this drug results in cumulative dose related cardiotoxicity due to enhanced production of free radicals leading to oxidative stress. Our earlier investigations have demonstrated significant antioxidant, anti-inflammatory and antitumour properties of Ganoderma lucidum extracts. We extended our investigations to evaluate the protective effect of Ganoderma lucidum extract against doxorubicin-induced cardiotoxicity. Administration of 3 doses of doxorubicin, 6 mg/kg body weights, i.p. per each dose, alternative days, showed dear signs of cardiotoxicity in rats. The drug enhanced serum creatine kinase (CK) activity and lipid peroxidation in tissue drastically. The drug also induced significant decrease in GSH level and activities of CAT, SOD and GPx. Administration of methanolic extract of G.lucidum (500 and 1,000 mg/kg body weight) significantly increased the level of GSH and activities of CAT, SOD and GPx. Activity of CK was significantly lowered in a dose dependent manner. The treatment also caused significant decrease in lipid peroxidation (MDA). The results thus indicated that methanolic extract of G.lucidum prevented oxidative stress caused by doxorubicin administration and the increase in serum CK activity and lipid peroxidation in the tissue. The experimental findings suggest the therapeutic potential of G.lucidum as adjuvant in cancer chemotherapy.

• Clinical and Experimental Pediatrics
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• 제46권3호
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• pp.242-249
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• 2003

목 적 : 항암치료 중 anthracycline을 사용한 환아들에 대한 후향적 조사를 통해 anthracycline의 축적량과 anthracycline 심독성과의 관계를 알고자 했고 심독성 환아들에 대한 추적 조사를 통해 anthracycline 심독성 환아의 예후를 알고자 하였다. 방 법 : 1995년 1월부터 2000년 12월까지 서울대학교병원 소아과에서 anthracycline을 포함한 항암치료를 시작한 환아를 대상으로 과거 anthracycline 축적량과 심장 초음파 검사 소견, 심독성 발생 유무 등을 조사하였다. 심독성은 좌심실 수축분율이 26% 이하로 감소한 경우로 정하였고 이들을 다시 좌심실 수축분율이 20%가 넘는 경증 심독성과 20% 미만인 중증 심독성으로 분류하였다. Anthracycline 심독성이 발생한 환아들에게 운동 능력과 심장 초음파, 심전도 검사, 흉부 방사선 촬영 등의 추적 검사를 시행하였다. 결 과 : 총 조사대상 환아는 154명이었다. 이 중에서 40명(26.0%)의 anthracycline 심독성이 발생하였으며 경증 심독성이 27명(17.5%), 중증 심독성이 13명(8.4%)이었다. 심독성의 발생률은 anthracycline의 축적량이 증가함에 따라 서서히 증가하다가 축적량이 $300mg/m^2$ 이상부터 갑자기 지수적으로 증가하는 양상을 보였다. 심독성 환아 40명 중 12명이 추적조사 이전에 사망하였고 생존한 환아 중 23명에 대해 추적검사를 시행하였다. Anthracycline의 사용을 중단한 후 평균 $3.6{\pm}1.8$년의 추적검사 결과 심독성 환아들의 좌심실 수축분율은 유의하게 증가하였다(P<0.01). 흉부 방사선 촬영이나 심전도 검사는 심독성의 진단을 위해 민감도와 특이도가 매우 낮은 검사였다. 결 론 : 일반적으로 anthracycline 심독성 환아의 추적검사로 시행하는 심전도 검사나 흉부 방사선 촬영은 심독성의 추적 조사에 도움이 되지 않는다. 심독성 환아들은 일단 생존하여 항암치료를 마치고 약 2-5년 정도 경과하면 심부전 증상이나 심장초음파 검사상 대부분 호전을 보인다.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.333-342
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• 2001

Adriamycin is a commonly used chemotherapeutic agent for cancer, including acute leukemia, lymphoma, and a number of solid human tumors. However, recent studies have recognized severe cardiotoxicity after an acute dose, which are likely the result of generation of free radicals and lipid peroxidation. Therefore, the clinical uses of adriamycin have been limited. Melatonin, the pineal gland hormone known for its ability to modulate circardian rhythm, has recently been studied in its several functions, including cancer growth inhibition, stimulating the immune system, and acting as an antioxidant and radical scavenging effects. In the present study, we evaluated the effect of melatonin administration on adriamycin-induced cardiotoxicity in rat. Heart slices were prepared using a Stadie-Riggs microtome for the measurement of malondialdehyde (MDA) content used as an index of lipid peroxidation and lactate dehydrogenase (LDH) release as an indicator of lethal cell injury. Serious adriamycin-induced lethality was observed in rat by a single intraperitoneal injection in a dose-dependent manner. A single injection of adriamycin (25 mg/kg, i.p.) induced a lethality rate of 86%, with melatonin (10 mg/kg s.c. for 6 days) treatment reducing the adriamycin-induced lethality rate to 20%. The severe body weight loss caused by adriamycin was also significantly attenuated by melatonin treatment. Treatment of melatonin marked reduced adriamycin-induced the levels of MDA formation and LDH release. A cell damage indicated by the loss of myofibrils, swelling of the mitochondria as well as cytoplasmic vacuolization was seen in adriamycin-treated group. Melatonin attenuated the adriamycin-induced structural alterations. These data provide evidence that melatonin prevents adriamycin-induced cardiotoxicity and might serve as a combination with adriamycin to limit free radical-mediated cardiotoxicity.

• 대한종양외과학회지
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• 제14권2호
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• pp.102-107
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• 2018

Purpose: Cardiotoxicity is a serious late complication of breast cancer treatment. Individual treatment risk of specific drugs has been investigated. However, studies on the evaluation of the composite risk of chemotherapeutic agents are limited. Methods: We retrospectively analyzed the medical records of breast cancer patients who received adjuvant treatment and had available serial echocardiography results. Patients were assigned to subgroups based on chemotherapy containing anthracyclines (A), anthracyclines and taxanes (A+T), and radiotherapy (RT). The development of cardiac disease and serial ejection fraction (EF) were reviewed. EF decline up to 10% from baseline was considered grade 1 cardiotoxicity and EF decline >20% or absolute value <50% was considered grade 2 cardiotoxicity. The most recent medical records and echocardiography results over 1 year of chemotherapy completion were also reviewed. Late cardiotoxicity was defined as a lack of recovery of EF decline or aggravated EF decline from baseline. Results: In total, 123 patients were evaluated. A small reduction in EF was observed after chemotherapy in both chemotherapy groups. There were no significant differences between groups A and A+T in EF decline following chemotherapy. We could not find any differences in composite risk between the chemotherapy groups and the RT group during follow-up. Late cardiotoxicity was seen in 15.45% of patients. During follow-up, three patients were diagnosed with dilated cardiomyopathy. Conclusion: There was no significant composite risk elevation following adjuvant treatment of breast cancer. However, late cardiotoxicity was considerable and further research in this direction is necessary.

• 대한한의학회지
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• 제42권3호
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• pp.44-55
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• 2021

Objectives: As the use of herbal medicinal products (HMPs) increases worldwide, systematic verification of the safety of HMPs is required. The induction of cardiotoxicity is one of the major factors in post-approval withdrawal of medicinal products, and drug-induced cardiotoxicity assessment is emerging as an important step in drug development. In the present study, we evaluated human ether-à-go-go-related gene (hERG) potassium channel-related cardiotoxicity to predict the risk of cardiac arrhythmia in thirteen herbal medicines known to have cardiac toxicity. Methods: We measured the inhibition rate of hERG potassium channel activity of 13 medicinal herbal extracts in hERG-expressing HEK 293 cells using an automated patch-clamping system. Quinidine was used as a positive control for inhibition of hERG activity. Results: Extracts of Evodiae Fructus, Strychni Semen, and Corydalis Tuber potently inhibited the activity of hERG, and IC₅₀ values were 3.158, 19.87, and 41.26 ㎍/mL, respectively. Cnidi Fructus, Ephedra Herba, Lithospermi Radix, Polygoni Multiflori Radix, Visci Ramulus et Folium, Asiasari Radix et Rhizoma, and Scolopendra weakly inhibited hERG activity, and the IC₅₀ value for each herbal medicine was more than 400 ㎍/mL. Aconiti Kusnezoffii Tuber and two types of Aconiti Lateralis Radix Preparata (Po and Yeom) had weak inhibitory activity against hERG, and the IC₅₀ values were more than 700 ㎍/mL. The IC₅₀ value of quinidine against hERG was 1.021 𝜇M. Conclusion: Evodiae Fructus, Strychni Semen, and Corydalis Tuber acted as potent inhibitors against hERG. These herbal medicines may cause cardiac arrhythmia through QT prolongation, so care should be taken when taking them.

• Journal of Nutrition and Health
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• 제33권7호
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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.