• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.5
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• pp.1243-1250
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• 2003

This study was designed to elucidate the synergistic cytotoxic mechanisms of the co-treatment of adriamycin and Paljinhangahm-dan in human hepatoma malignant cancer cell line, HepG2. The combination of adriamycin and the ethanol extract of Paljinhangahm-dan synergistically augmented the cytotoxicity of Adriamycin and Paljinhangahm-dan in HepG2 cells. The cytotoxicity of two drugs was revealed as apoptosis characterized by DNA fragmentaton in agarose gel electrophoresis. The apoptotic cytotoxicity of adriamycin and Paljinhangahm-dan was accompanied by the cleavage of procaspase -3 protease and PARP. Of note, anti apoptotic Bcl2 protein was obviously decreased, but Fas was dramatically increased in HepG2 cells co-treated with Adriamycin and Paljinhangahm -dan. In addition, through 2-D gel electorphoresis, we observed that the expression levels of a lot of proteins were obviously changed by the status of drug treatments. This results suggest that the synergistic cytotoxicity of the co-treatment of adriamycin and Paljinhangahm-dan might be caused by the changes of the expression levels of a lot of proteins which play pivotal roles in cell survival or death.