• Title, Summary, Keyword: adriamycin

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The effect of selenium on renal lesions induced by adriamycin in rats (Selenium이 adriamycin에 의해서 유발되는 랫드 신장병변에 미치는 영향)

  • Park, Eun-sung;Lee, Joon-sup
    • Korean Journal of Veterinary Research
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    • v.37 no.1
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    • pp.41-57
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    • 1997
  • This study was carried out to investigate the effect of selenium on the adriamycininduced renal lesions in male Sprague Dawley rats. A total of 60 Sprague-Dawley male rats were divided into 2 control groups(C1: saline, C2: selenium) and 2 treatment groups(T1: adriamycin, T2: adriamycin+selenium). The rats of the C1 and T1 groups were given normal saline(0.15ml/rat), the rats of the C2 and T2 groups were given sodium selenite(0.5mg/kg) intraperitoneally three days a week for 4 weeks. The treatment groups were dosed intraperitoneally with adriamycin(2mg/kg/day) five days at the second week. Animals were sacrificed at the 1st week, 2nd week and 3rd week after dosing with adriamycin. The morphologic abnormalities of the glomeruli and tubules in the kidney of male rats were examined histopathologically and electron microscopically.The results obtained were as follows : The mean body weight of adriamycin dosed group was significantly decreased as compared with that of control group at 4th week(p<0.05). In adriamycin and selenium dosed group, the mean body weight was decreased until the end of 2nd week but gradually increased from 3rd to 4th week. The histopathological findings of the renal corpuscle in adriamycin dosed group were parietal epithelial cell proliferation, vacuolization of glomerulus, and thickened basement membrane of the parietal epithelium. Proximal convoluted tubules were significantly dilated and the lumens were filled with renal cast. These lesions were generally not very significant in the rats given adriamycin and selenium. The electron microscopical findings of the renal glomerulus in the adriamycin dosed group were focal loss and fusion of the pedicels of the podocyte, and some vacuoles in the cytoplasm of the podocytes. There were numerous cytoplasmic vacuoles in the proximal and distal convoluted tubular cells. However, these ultrastructural changes were not significantly observed in the renal tubules of the rats of adriamycin and selenium dosed group. These results suggest that selenium may act as an inhibitor of the renal lesions induced by adriamycin in male rats.

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The Protective Effect of Melatonin Administration against Adria-mycin-induced Cardiotoxicity in Rats

  • Han, Jin;Kim, Chung-Hee;Kim, Na-Ri;Park, Ju-Hee;Yang, Young-Churl;Kim, Eui-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.4
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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.

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Effects of DMTU and SOD on Ultrastructural Changes of Gastric Chief Cells in Adriamycin Treated Rats (Superoxide dismutase 및 Dimethyl thiourea가 흰쥐 위샘 으뜸세포에서 Adriamycin 투여 후 나타나는 미세구조의 변화에 미치는 영향)

  • Paik, Doo-Jin;Chang, Hyung-Shim;Chung, Ho-Sam
    • Applied Microscopy
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    • v.28 no.2
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    • pp.225-236
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    • 1998
  • Adriamycin is a one of anthracyclin antibiotics isolated from the culture media of Streptomyces peucetius var casius. The formation of reactive oxygen metabolite by redox cycling during the metabolism and the inhibition of DNA synthesis results in antineoplastic effects of adriamycin. The authors have demonstrated the effects of SOD(superoxide dismutase) or DMTU (dimethyl thiourea), which are used as an antioxidant, on the ultrastructural changes of the gastric chief cells after the administration of adriamycin in the rat. Adriamycin (30 mg/kg) was administered intraperitoneally to the Sprague-Dawley rats weighing about 220 gm and SOD (15000 unit/kg) or DMTU (500 mg/kg) were administered intraperitoneally to the rats 30 minutes after the administration of adriamycin. The gastric chief cells 24, 48 and 72 hours after the administration of adriamycin were observed with Hitachi-600 electron microscope. The results were as follows. 1. SOD or DMTU alone did not affect the ultra structures of the gastric chief cells in the rat. 2. Dilation, sacculation and segmentation of the cisternae of rough endoplasmic reticulum, dilation of the saccules of Golgi complex and dilated mitochondria with electron lucent matrix were seen in the adriamycin treated rats. In the course of time, the ultrastructures of the chief cell changed markedly. 72 hours after drug administration, severely dilated cisternae of rough endoplasmic reticulum, with clumping of chromatin around the nuclear envelope and mitochondria with electron lucent matrix and dilated cristae were seen in the chief cell. 3. The treatment of SOD is more effective than DMTU to attenuated the ultrastructural changes of the chief cells in the adriamycin administered rat. Consequently it is suggested that adriamycin would induce the degenerative changes of the organelles of the chief cell. The treatment of SOD is more effective than DMTU to attenuate the adriamycin induced damage.

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Cytotoxic Effect of Adriamycin in Cultured Skin Cells of Fetal Rat (백서 태자의 배양 피부세포에서 Adriamycin의 세포독성에 관한 연구)

  • Lee, Kyeong-Hun;Lee, Sang-Yeul;Kim, Chin-Whan;Kim, Yong-Sik;Kim, Myung-Suk
    • The Korean Journal of Pharmacology
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    • v.27 no.2
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    • pp.197-205
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    • 1991
  • Local extravasation during intravenous administration of adriamycin (doxorubicin HCl) can cause severe skin ulceration and necrosis. To investigate the mechanism of adriamycin-induced skin toxicity, effects of adriamycin on reactive oxygen radical metabolism using cultured skin cells of fetal rat. Adriamycin produced significant release of lactic dehydrogenase from cultured skin cell preparations dose- and time-dependently. The production of superoxide anion in sonicated suspensions of cultured skin cells was significantly increased by adriamycin under the presence of NADPH and NADH. The drug also stimulated malondialdehyde (MDA) production, an index of lipid peroxidation, in NADPH- and NADH-supported cell preparations. The increased production of MDA was significantly inhibited by oxygen radical scavengers (superoxide dismutase, catalase, thiourea) and antioxidants (butylated hydroxytoluene, ${\alpha}-tocopherol$). Treatment of cultured skin cells with 1, 3,-bis (2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase, enhanced the lipid peroxidation induced by adriamycin. The present study suggests that lipid peroxidation which is resulted from the stimulated production of reactive oxygen radical causes cellular damage in adriamycin-treated skin cells of rat.

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The Combined Effect of Adriamycin and Irradiation on the Small Intestinal Villi of Mice (방사선 조사와 Adriamycin 병용 투여가 마우스 소장에 미치는 영향에 관한 연구)

  • Hong, Seong-Eon;Ahn, Chi-Yul
    • Radiation Oncology Journal
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    • v.4 no.1
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    • pp.1-13
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    • 1986
  • In order to clarify the effect of radiation on the mouse jejunal crypt cells by combined administration of administration and radiation and also to evaluate the enhancing effect of adriamycin, the authors performed this study by delivering single irradiation of 1,000 to 1,600 rad to the whole abdomen of mice by cobalt-60 teletherapy unit. In combination with adriyamycin treatment groups, the drug was administered as single dose of 10 mg/kg either 2 hours before or 4 hours after graded single dose,900 to 1,400 rad, of irradiation. The authors studied the quantitative changes of intestinal crypt cells by microcolony survival assay technique and the morphological changes of small intestinal villi by scanning electron microscope in mice following to combined therapy with adriamycin and irradiation, The average number of jejunal crypts per circumference was $130{\pm}16$ in control group. The mean lethal dose(Do) of each irradiation alone and combined therapy groups 2 hours before and 4 hours after irradiation, were 160, 170, and 170 rad in cell survival curves, respectively. The dose effect factor(DEF) of adriamycin in each groups of pre-irradiation and post-irradiation were 1.19 and 1.26, respectively. The conical shaped villi were noted on 1,200 rad in irradiation alone group and 1,000 rad in combined groups. For the proper clinical application we must be careful of the radiation injury to small bowel when the anticancer chemotherapy and radiation therapy to the abdomen and pelvic area are used as combined therapeutic modality.

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Effect of Ampelopsis radix on the Toxicity of Adriamycin (Adriamycin의 독성 발현에 미치는 백렴(Ampelopsis radix)의 영향)

  • Kim, Dong-Seok;Lee, Seong-Ho;Jeong, Yeon-Bong
    • The Korean Journal of Food And Nutrition
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    • v.7 no.3
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    • pp.232-238
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    • 1994
  • Adriamycin is a major cancer chemotherapeutic agent against a me range of human neoplasms. However, its clinical application is limited since It has a variety of side effects, bone marrow suppression and cardiotoxity, and this toxicity appears by free radical. This study investigated the effect of Ampelopsis radix on the toxicity of adriamycin. The methanol fraction reduced slightly adriamycin induced lipid peroxidation and superoxide production at the dose of 50mg /kg. 1.p., respectively. During the adriamycin administration. Protein bound-SH, nonprotein bound-SH, and glutathione-5-transferase did not change, but methanol fraction treated group were markedly increase. These results indicated that Ampelopsis radix has a major influence on the thiol group and related enzyme activity on the antioxidative effects.

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Studies on the Adriamycin produced from Streptomyces peucetius var. caesius Part 1. Isolation of Mutant (Streplomyces peucetius var. caesius에 의한 Adriamycin 생산(生産)에 관한 연구(硏究) 제1보(第一報). 변이주의 분리)

  • Won-Cheol, Shin
    • Journal of Industrial Technology
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    • v.2
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    • pp.21-25
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    • 1982
  • This study was to investigate the basic research about Adriamycin production from Streptomyces peucetius var. caesius. Streptococcus pyogenes(YUFE 2204) was sensitive against Adriamycin and its MIC value was $3.125{\mu}g/ml$. Several mutants were isolated by UV-light. Among 325 mutants, Streptomyces peucetius var. caesius YS-107 was showed highest productivity of Adriamycin.

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Inhibitory Mechanism of a New Antitumor Agent DA125 on DNA Replication (새로운 항암제 DA-125의 유전자 복제 억제 기작)

  • 이상광;김도진;오유택;이상득;우은란;신차균
    • YAKHAK HOEJI
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    • v.43 no.5
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    • pp.623-628
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    • 1999
  • DA-125, a new antitumor agent, was compared with adriamycin, a known DNA intercalator, in terms of inhibitory mechanism of DNA replication by using replicating simian virus 40 (SV40) genome in vivo. In analyzing the SV40 DNA replication intermediates present in cells treated with DA-125, it was not observed to accumulate B-dimers of SV40 DNA which are prominent in adriamycin-treated cells. However, treatment with DA-125 induced dose-dependent formation of DNA-topoisomerase complex which is characteristic of topoisomerase poisons. In addition, DA-125 showed more efficient in inhibiting SV40 DNA replication than adriamycin. Therefore, on the basis of this observation, we suggest that DA-125, a derivative of adriamycin, inhibits DNA replication by blocking topoisomerase activity as a toposomerase poison although adriamycin blocks topoisomerase activity as a DNA intercalator.

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Development of Specific Organ-Targeting Drug Delivery System (III)-In Vitro Study on Liver-Targeting Adriamycin Delivery System using Human Serum Albumin Microspheres- (장기표적용 약물수송체의 개발에 관한 연구(제 3보 -알부민 미립구를 이용한 Adriamycin의 간 표적용 수송체에 관한 in vitro 연구-)

  • Kim, Chong-Kook;Hwang, Sung-Joo;Yang, Ji-Sun
    • Journal of Pharmaceutical Investigation
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    • v.19 no.4
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    • pp.195-202
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    • 1989
  • In attempt to improve the chemotherapeutic activity of adriamycin, adriamycin-entrapped HSA microspheres were prepared and investigated by the various in vitro experiments. The shape, surface characteristics and size distribution of HSA microspheres are observed by scanning electron microscopy. The in vitro drug release, albumin matrix degradation by protease of HSA microspheres were studied. The shape of HSA microspheres were spherical and the surface was smooth and compact. The size of HSA microspheres ranged from 0.4 to $2.5\;{\mu}m$ and have average diameters of 0.5 to $0.7\;{\mu}m$. The size distribution of HSA microspheres prepared by ultrasonication was mainly affected by albumin concentration and heating time in the process of hardening. In in vitro, almost all adriamycin was released from HSA microspheres for 8 hr. Analysis of the resulting adriamycin release profiles demonstrated that adriamycin is released from the microspheres in two distinct steps, a fast phase (until 30 min) followed by a much slower sustained release phase. Drug release, which is due to diffusion, was depended on the rate of matrix hydration. Drug release was largely affected by albumin concentration and heating temperature during the process of hardening. Albumin matrix degradation of HSA microspheres was affected by heating temperature and albumin concentration. Higher temperature and longer times generally produce harder, less porous, and slowly degradable microspheres.

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Suppressive Effect of N-Acetylcysteine on the Adriamycin-Induced Micronuclei Formation in Mouse Bone-marrow Cells (생쥐 골수세포에서 아드리아마이신의 소핵생성에 미치는 N-마세틸시스테인의 억제효과)

  • 손수정;허인회;최성규;허문영
    • YAKHAK HOEJI
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    • v.37 no.3
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    • pp.278-285
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    • 1993
  • The anticlastogenic effect of N-acetylcysteine was tested in vivo in mouse bone-marrow micronucleus assay. The frequencies of micronuclei induced by adriamycin (5 mg/kg i.p.) in bonemarrow cells were decreased by the oral administration of N-acetylcysteine at 12 h before adriamycin injection. The observed suppressing effect was not a reflection of a delay in the formation of micronuclei by the cytotoxic effect of N-acetylcysteine. The anticlastogenic effects of SH compound including N-acetylcysteine, cysteine, cystine, S-carboxy methylcysteine and glutathione were also investigated by the multiple pretreatment. Each SH compound was administered orally every day for 5 days and adriamycin (5 mg/kg i.p.) was injected at 24h after the last dose of test compound. N-acetylcysteine and glutathione showed significantly the suppressive effect at dose of 10 and 25 mg/kg for N-acetylcysteine and at the dose of 25 mg/kg for glutathione. Our study suggests that N-acetylcysteine is capable of protecting the chromosomal damages in the normal cells during cancer chemotherapy by adriamycin, and may act as an anticlastogen against induction of micronuclei by superoxide generating agent such as adriamycin.

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