• Archives of Pharmacal Research
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• v.16 no.2
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• pp.129-133
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• 1993

Temperature sensitive liposomes(TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drug, Lipid compositions of TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition of TSL using a differential scanning calorimetry (DSC) was also investigated. Phase transition temperature $(T_c)$ of TSL was dependent on the lipid compositions of TSL ADM broadened thermogram of TSL but Ara-C did not. However, $T_c$ of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near $T_c$ and observed at $39-41^\circ{C}$ for DPPC (Dipalmitoylphosphatidylcholine) only, $52-54^\circ{C}$ for DPPC and DSPC (1:1), respectively. Effect of human serum alburmin (HAA) on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below $T_c$. However, ADM release from TSL was increased at the near and above $T_c$. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near TEX>$4^\circ{C}$. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at TEX>$4^\circ{C}$ was not changed, the TSL was considered to be stable for at least 1 week at TEX>$4^\circ{C}$. Based on these findings, TSL may be useful to deliver drugs to preheated target sites due to its thermal behaviors.

• Journal of Pharmacopuncture
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• v.22 no.1
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• pp.35-40
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• 2019

Objective: Adriamycin (ADR) is an important anti-cancer drug which can cause renal toxicity. Given the known anti-inflammatory and antioxidant effects of Plantago major (P. major), the aim of this study was to determine the effects of hydroalcoholic extract of P. major on ADR- induced nephropathy in rats. Methods: Fifty male Wistar albino rats were randomly divided into 5 groups including: control, ADR (5 mg/kg), ADR + P. major (600 and 1200 mg/kg) and P. major (1200 mg/kg). The animals were treated with P. major extract for 5 consecutive weeks and ADR was intravenously injected on the 7th day of the study. Urine and serum samples were collected on days 0, 14, 21, 28, and 35 for the measurement of serum cholesterol and albumin levels and urine protein excretion rate. At the end of the study, the left kidneys were removed for apoptosis assessment. Results: Administration of ADR significantly decreased serum albumin level and increased serum cholesterol and urine protein excretion rate as well as, apoptotic cell numbers compared to the control group (P < 0.001) while had no effect on glomerular filtration rate (P > 0.05). Treatment with P. major, in both 600 and 1200 mg/kg doses, increased serum albumin level and decreased serum cholesterol concentration, urine protein excretion rate and as well as the number of apoptotic cell compared to the ADR group (P < 0.001). Conclusion: Our results showed that the P. major extract effectively protects against ADR- induced nephropathy by reducing kidney apoptosis and improving renal functioning in rats.

• Clinical and Experimental Pediatrics
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• v.45 no.2
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• pp.214-222
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• 2002

Purpose : The aim of this study was to evaluate myocardial injury in children treated with adriamycin by echocardiography, which is non-invasive and safe measurement for children. Methods : Left ventricular dimensions, wall stress, and contractile function were determined by echocardiographic methods in 17 patient recepients with adriamycin chemotherapy at rest(group 1) and during stress(group 2). Twenty age-matched normal subjects were established as control group. Results : End-diastolic dimension was decreased in both groups(group 1; $92{\pm}7%$ of normal, group 2; $87{\pm}8%$ of normal, P<0.05). Left ventricular end diastolic volume and wall mass were also decreased in both groups(group 1; $96{\pm}12mL/m^2$ and $145{\pm}18g/m^2$, group 2; $87{\pm}8mL/m^2$ and $137{\pm}16g/m^2$, respectively, P<0.05 and P<0.05) and group 2 showed lower values than group 1. Meridional end systolic stress(ESSm) was increased in both groups but there was no significant difference between the two groups(group 1; $52.6{\pm}6.2g/cm^2$, group 2; $63.5{\pm}8.5g/cm^2$, P<0.05, normal value $45.7{\pm}3.5g/cm^2$). The load-independent relation of rate-corrected circumferential fiber shortening velocity(Vcfc) to ESSm has a significant abnormal change in 7 out of 17(41%) in group 1 and 12 out of 17(71%) in group 2. Conclusion : The load-dependent systolic index, such as fractional shortening, may fail to show abnormality because of the compensatory changes in preload and afterload which can mask the impaired contractility. Therefore, systolic performance also should be monitored by a load-indepedent contractility index such as slope value of the end-systolic pressure-dimension relation and the position of the left ventricular stress-fiber shortening velocity after exercise.

• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.432-444
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• 1993

Multidrug resistance(MDR) phenotype is frequently observed in animal and human cancer cell lines selected for in vitro resistance to a single chemotherapeutic agent. It is characterized by the diminished drug accumulation and is related to the drug efflux mechanism in resistant cells. In the present study, adriamycin resistant cells(L1210-$AdR_6$ : $10^{-6}M$ adriamycin, $-AdR_5$ : $10^{-5}M$) and vincristine resistant cells (L1210-$VcR_7$ : $10^{-7}M$ vincristine, $-VcR_6$ : $10^{-6}M$) were produced from mouse lymphoblastic leukemia cell line L1210. Growth profiles of survived cells were observed for 5 days with MTT(thiazolyl blue) assay and resistance was compared with $IC_{50}$(drug concentration of 50% survival reduction in absorbance). Resistant cells proliferated more slowly than sensitive cell. Doubling times were 29.7hr in L1210, 68.7hr in L1210-$AdR_5$ and 58.2hr in $-VcR_6$. MDRs expressed as resistance factor were as follows, L1210-$AdR_5$ was 76.4 times for vincristine, L1210-$VcR_6$ was 96.4 times for adriamycin. The cell membrane proteins with three different M.W. were recognized to be related resistance, 220, 158, and 88 kd in L1210-$AdR_5$, 158, 140 and 88 kd in L1210-$VcR_6$ by SDS-PAG electrophoresis. Cell surface membrane proteins were identified by radio-iodination and autoradiogram, their molecular weights were 158, 72.8, and 42.4 Kd in L1210-$VcR_6$.

• Clinical and Experimental Pediatrics
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• v.45 no.12
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• pp.1534-1539
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• 2002

Purpose : This study was designed to exclude radiation in advanced(stage 3, 4) Wilms tumor (WT) by increasing the chance of complete surgical removal with preceding neoadjuvant chemotherapy, thereby reducing the incidence of late effects. Methods : Between December 1998 and July 2002, we conducted neoadjuvant chemotherapy after needle aspiration biopsy on patients who had advanced WT. If needle biopsy was accessible, we conducted neoadjuvant chemotherapy(vincristine, adriamycin, dactinomycin) for 12 weeks and then performed surgical removal, excluded radiation therapy and conducted postoperative chemotherapy (vincristine, dactinomycin${\pm}$adriamycin). In other cases, we firstly conducted the operation and then performed radiation and postoperative chemotherapy. Results : Of the 17 patients diagnosed as WT, 12 patients had an advanced stage of disease. In two of the 12 patients, initial surgical removal was conducted. The median age of patients was 21 months(5-103 months). Of the 10 the patients who received neoadjuvant chemotherapy, eight patients were stage 1, one patient was stage 2, and the other was stage 3 at operation. In nine patients except one with stage 3 disease, we could perform complete surgical resection and therefore could omit radiation. In four cases we could also exclude adriamycin after operation. All but one patient was alive, disease-free, for a median follow-up of 21 months(9-43 months). Conclusion : After neoadjuvant chemotherapy, we could increase the chance of complete tumor resection, exclude radiation and decrease the intensity of postoperative chemotherapy in selected cases. Long term follow-up is needed to determine whether our method would significantly decrease late effects.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.145-150
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• 1990

Mesna has been used with ifosfamide to prevent urotoxicity in the treatment of testicular cancers. This drug also protected the toxicities of adriamycin without compromising cytostatic activity. With an idea of radioprotective role of sulfhydryl group of radioprotectors and of mesna decreasing the toxic effect of adriamycin which produces free radicals, mesna and radiation were administered to mice to study the protective effect of this drug and to identify the difference in regenerative capacity of the germ cells in the testis between radiation-treated and both mesna-and radiation-treated groups. The shape and numbers of spermatogenic cells in the seminiferous tubules were examined every week after irradiation. In both groups, initial reduction and later recovery in germ cell numbers and shape was observed. The lowest germ cell number was found around three weeks after irradiation. Mean germ cell number of the mesna-treated group was significantly higher than radiation-treated group at all observed periods (p<0.05). More competent regeneration was present in mesna-treated group. These results suggest that mesna protect the testis from radiation injury. Further study will be necessary to identify whether mesna protects other tissues from radiation and it does not hamper tumor control.

• Journal of Nutrition and Health
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• v.24 no.4
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• pp.299-307
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• 1991

The present study was designed to evaluate the effects of dietary coenzyme $Q_{10}$ on mitochondrial coenzyme $Q_{10}$ and fatty acid composition in adriamycin (ADR)-treated rats. Two experiments were conducted in rats. Experiment 1 was undertaken under the condition of simultaneous administration of ADR and coenzyme $Q_{10}$ for 4 weeks. Experiment 2 was undertaken under the same condition as experiment 1 after feeding the experimental diets alone without administration of ADR for 4 weeks. Heart mitochondrial coenzyme $Q_{10}$ level of rats was greatly decreased by ADR treatment. but higher level of dietary coenzyme $Q_{10}$ elevated this decrease to control ranges. Pretreatment with dietary supplementation of coenzyme $Q_{10}$ showed a significant increase in myocardial coenzyme $Q_{10}$ level. With ADR treatment. polyunsaturated fatty acids such as arachidonic acid (20 : 4) and docosahexaenoic acid (22 : 6) were decreased. However, dietary supplementation of coenzyme $Q_{10}$ modified this decrement to some extent. In both experiment 1 and 2. the polyunsaturated fatty acids/saturated and polyunsaturated fatty acids (P/S+ M) ratio of ADR-treated rats tended to be lower than that of control rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.5
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• pp.484-489
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• 1992

The present study was designed to evaluate the effects of dietary coenzyme $Q_{10}$ and vitamin E on hepatic lipid metabolism changes in adriamy cin(ADR)-treated rats. ADR treatment significantly increased the plasma levels of lipid peroxide in rats. But this increase was reduced by dietary supplementation of coenzyme $Q_{10}$ or vitamin E. Catalase and glutathione peroxidase activities were not greatly changed by ADR treatment, but the activities were significantly increased by dietary coenzyme $Q_{10}$. There was a tendency of lower superoxide dismutase activity in ADR-treated rats. However, coenzyme $Q_{10}$ administration induced this enzyme activity. The contents of cholesterol and phospholipid in liver were elevated by ADR-treated. Dietary coenzyme $Q_{10}$ reduced the increased hepatic cholesterol content in ADR-treated rat.

• Childhood Kidney Diseases
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• v.14 no.1
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• pp.32-41
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• 2010

Purpose : Glomerulonephropathy (GN) often manifests as proteinuria and progresses to chronic renal failure without specific therapy. Mesenchymal stem cell (MSC) has been tried as a therapeutic agent in experimental GN, and previous studies showed that administration of MSC concomitantly to the insult inducing GN or via intra-renal administration ameliorated proteinuria. The purpose of this study was to test the therapeutic potential of MSC administered via intravenous route at the time of clinically evident proteinuria. Methods : MSCs were administered intravenously via tail vain into the mice with adriamycin (ADR) induced nephropathy (ADR-GN), two weeks after ADR injection when massive proteinuria was evident. To test the capacity of MSC modulate the cytokine production in the inflammatory milieu, the concentrations of IFN-$\gamma$ and IL-10 were measured in the supernatant of in vitro mixed lymphocyte culture (MLC) with or without additional MSC. Results : MSCs administered intravenously into the proteinuric mice with ADR-GN accelerated the recovery of this experimental GN with disappearance of proteinuria in two weeks when the saline treated (control) mice still showed significant proteinuria. The mice treated with MSC also had a tendency of better survival. Addition of MSC decreased IFN-$\gamma$ and increased IL-10 in the supernatant of MLC. Conclusion : This study showed that MSC had a therapeutic potential even when administered in a more clinically relevant setting into a proteinuric glomerulonephropathy model. Further study to verify the mechanism and long-term safety of this phenomenon is required.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.273.2-274
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• 2000