RESUMEN
New insights about nanomaterials' biodistribution revealed their ability to achieve tumor accumulation by taking advantage from the dynamic vents occurring in tumor's vasculature. This paradigm-shift emphasizes the importance of extending nanomaterials' blood circulation time to enhance their tumor uptake. The classic strategy to improve nanomaterials' stability during circulation relies on their functionalization with poly(ethylene glycol). However, recent reports have been showing that PEGylated nanomaterials can suffer from the accelerated blood clearance phenomenon, emphasizing the importance of developing novel coatings for functionalizing the nanomaterials. To address this limitation, the modification of natural carriers' surface to enhance their stability appears to be a promising strategy. Herein, sulfobetaine methacrylate (SBMA)-functionalized bovine serum albumin (BSA) was synthesized for the first time to investigate the capacity of this modification to improve the resulting nanoparticles' physicochemical properties, colloidal stability and in vitro performance. This novel polymer was then employed in the formulation of nanoparticles loaded with IR780 for application in breast cancer phototherapy (IR/SBMA-BSA NPs). When compared to their non-functionalized equivalents, the IR/SBMA-BSA NPs presented a neutral surface charge and a higher stability in biologically relevant media. Due to these features, the IR/SBMA-BSA NPs could achieve a 1.9-fold greater uptake by breast cancer cells than IR/BSA NPs. Furthermore, the IR/SBMA-BSA NPs were cytocompatible towards normal cells and reduced breast cancer cells' viability up to 42%. The phototherapy mediated by IR/SBMA-BSA NPs could further decrease cancer cells' viability to about 12%. Overall, the IR/SBMA-BSA NPs have enhanced features that propel their application in breast cancer phototherapy.
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Neoplasias de la Mama/tratamiento farmacológico , Portadores de Fármacos , Indoles/farmacología , Metacrilatos/química , Nanopartículas , Fármacos Fotosensibilizantes/farmacología , Fototerapia , Albúmina Sérica Bovina/química , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Composición de Medicamentos , Estabilidad de Medicamentos , Femenino , Humanos , Indoles/química , Indoles/metabolismo , Células MCF-7 , Metacrilatos/toxicidad , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/metabolismo , Albúmina Sérica Bovina/toxicidad , Propiedades de SuperficieRESUMEN
ETHNOPHARMACOLOGY RELEVANCE: Yi-Shen-Hua-Shi (YSHS) granule is a modern Chinese patent drug for treating chronic glomerulonephritis (CGN). It is derived from a traditional Chinese medicine formula Sheng-Yang-Yi-Wei decoction that is used to treat CGN in ancient China. Pharmacological activities of YSHS granule have not been reported. In this work, we investigated the anti-CGN effects and TGFß signaling-related mechanism of action of this herbal drug. MATERIALS AND METHODS: The rat model of CGN was established by injection of cationization-bovine serum albumin (C-BSA) for five weeks. After finishing C-BSA injection, drugs were intragastrically administered to the rats once daily for four weeks. Clinical signs were recorded daily. Serum and urine biochemical parameters were analyzed by respective kits. Protein levels were examined by Western blotting. Pathological changes of renal tissues were evaluated by HE and Masson's trichrome staining. RESULTS AND CONCLUSIONS: No significant differences in clinical signs and body weights were found among normal, model and drug treatment groups. Proteinuria; albuminuria; increased urine volume; elevated urea nitrogen, creatinine, total cholesterol and triglyceride levels in sera; decreased serum total protein and albumin; as well as renal pathological damage and fibrosis were observed in CGN model rats. YSHS granule ameliorated all the abnormal behavioral and biochemical changes in the model rats. Mechanical investigations showed that YSHS granule down-regulated proteins levels of TGFß1, phospho-Smad2/3 (Thr 8) and Smad4 in rat renal tissues. In conclusion, YSHS granule demonstrates therapeutic effects in a rat model of CGN, and inhibition of the TGFß/Smad signaling pathway is involved in the mechanism of action of the granule. This study provides a pharmacological basis for the use of modern YSHS granule and ancient Sheng-Yang-Yi-Wei decoction in treating CGN.
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Medicamentos Herbarios Chinos/farmacología , Glomerulonefritis/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Enfermedad Crónica/tratamiento farmacológico , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Glomerulonefritis/inducido químicamente , Glomerulonefritis/patología , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Medicina Tradicional China , Patentes como Asunto , Fosforilación/efectos de los fármacos , Ratas , Ratas Wistar , Albúmina Sérica Bovina/toxicidad , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Proteína Smad4/metabolismo , Resultado del TratamientoRESUMEN
The leaf extract of Turraea vogelii Hook. f. ex. Benth. is used in ethnomedicine for the management of pain and inflammation. Anti-nociceptive activity was determined using acetic acid-induced mouse writhing model. The anti-inflammatory activity was investigated using in-vitro bovine serum albumin (BSA) denaturation assay and BSA-induced hind paw edema in rats. The extract (125-500 mg/kg) administered via the oral route produced a significant (p<0.005) inhibition of acetic acid-induced writhes. The percent inhibition of writhes for extract (500 mg/kg) and diclofenac (10 mg/kg) was 53.3 and 59.5% respectively. The methanol extract (10-6-1.0 µg/mL) inhibited protein denaturation with IC50values of (1.06 × 10-3 µg/mL and 2.58 × 10-3 µg/mL) for extract and diclofenac respectively. Furthermore, the leaf extract (62.5 mg/kg) significantly (p<0.05) inhibited BSA-induced paw edema in rats. The methanol leaf extract of T. vogelii has anti-nociceptive and anti-inflammatory activities. These findings justify the use of the plant in traditional medicine for the management of pain and inflammation.
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Analgésicos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Meliaceae/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Evaluación Preclínica de Medicamentos/métodos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Ratones , Hojas de la Planta/química , Plantas Medicinales/química , Ratas Wistar , Albúmina Sérica Bovina/administración & dosificación , Albúmina Sérica Bovina/toxicidadRESUMEN
BACKGROUND: The matrine-type alkaloids are bioactive components extracted from Sophora flavescens, which is used in treatment of diabetes mellitus in traditional Chinese medicine. Advanced glycation end products mediate diabetic vascular complications. This study was aimed to investigate the protective effects and molecular mechanisms of matrine-type alkaloids on advanced glycation end products-induced reactive oxygen species-mediated endothelial apoptosis. METHODS AND RESULTS: Rats aorta and cultured rat aortic endothelial cells were exposed to advanced glycation end products. Matrine-type alkaloids, p38 mitogen-activated protein kinase (MAPK) inhibitor, and small interference RNAs against p38 MAPK kinases MAPK kinase kinase (MKK)3 and MKK6 were administrated. Intracellular reactive oxygen species production, cell apoptosis, phosphorylation of MKKs/p38 MAPK, and expression levels of heme oxygenase/NADPH quinone oxidoreductase were assessed. The nuclear factor erythroid 2-related factor 2 nuclear translocation and the binding activity of nuclear factor erythroid 2-related factor 2 with antioxidant response element were also evaluated. Matrine-type alkaloids suppressed intracellular reactive oxygen species production and inhibited endothelial cell apoptosis in vivo and in vitro by recovering phosphorylation of MKK3/6 and p38 MAPK, nuclear factor erythroid 2-related factor 2 nuclear translocation, and antioxidant response element binding activity, as well as the expression levels of heme oxygenase/NADPH quinone oxidoreductase. p38 MAPK inhibitor treatment impaired the effects of matrine-type alkaloids in vivo and in vitro. MKK3/6 silencing impaired the effects of matrine-type alkaloids in vitro. CONCLUSIONS: Matrine-type alkaloids exert endothelial protective effects against advanced glycation end products induced reactive oxygen species-mediated apoptosis by targeting MKK3/6 and enhancing their phosphorylation.
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Alcaloides/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Productos Finales de Glicación Avanzada/toxicidad , MAP Quinasa Quinasa 3/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Albúmina Sérica Bovina/toxicidad , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Células Cultivadas , Citoprotección , Relación Dosis-Respuesta a Droga , Células Endoteliales/enzimología , Células Endoteliales/patología , MAP Quinasa Quinasa 3/genética , MAP Quinasa Quinasa 6/genética , MAP Quinasa Quinasa 6/metabolismo , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Fosforilación , Quinolizinas/farmacología , Ratas Sprague-Dawley , MatrinasRESUMEN
The underutilized Kenyan variety of Dolichos lablab bean seeds serve as a good source of natural antioxidants, which can probably be effective in reducing the risk of occurrence of several diseases. This study was undertaken for the first time to address the limited knowledge regarding the antioxidant activities of lablab beans. Moreover, their DNA damage inhibitory activity, bovine serum albumin (BSA) damage inhibitory activity, and the inhibition of acetylcholinesterase and porcine α-amylase were also investigated. The antioxidant capacity of Dolichos lablab bean seeds extracted with methanol, water or methanol/water combination was evaluated by the ferric-reducing antioxidant power (FRAP) assay, free radical-scavenging activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) radical-scavenging assay, and 2,20-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Results reported in the present study indicate that water, methanol and water/methanol extracts of lablab bean flour exhibited good antioxidant activity by effectively scavenging various free radicals, such as DPPH, NO, and ABTS radicals. The extracts also exhibited protective effects against DNA and BSA damage and inhibitory effects on porcine α-amylase. Findings of this study suggest that extracts from the lablab bean flour would have potential application in food supplements, and pharmaceutical and cosmetic industries.
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Inhibidores de la Colinesterasa/análisis , Daño del ADN/efectos de los fármacos , Dolichos/química , Depuradores de Radicales Libres/análisis , Extractos Vegetales/análisis , alfa-Amilasas/antagonistas & inhibidores , Acetilcolinesterasa/análisis , Animales , Bovinos , ADN/genética , Albúmina Sérica Bovina/toxicidad , Porcinos , alfa-Amilasas/análisisRESUMEN
Photothermal therapy as a physical therapeutic approach has greatly attracted research interest due to its negligible systemic effects. Among the various photothermal agents, CuS nanoparticles have been widely used due to their easy preparation, low cost, high stability and strong absorption in the NIR region. However, the ambiguous biotoxicity of CuS nanoparticles limited their bio-application. So it is highly desirable to develop biocompatible CuS photothermal agents with the potential of clinical translation. Herein, we report a novel method to synthesize biocompatible CuS nanoparticles for photothermal therapy using bovine serum albumin (BSA) as a template via mimicking biomaterialization processes. Owing to the inherent biocompatibility of BSA, the toxicity assays in vitro and in vivo showed that BSA-CuS nanoparticles possessed good biocompatibility. In vitro and in vivo photothermal therapies were performed and good results were obtained. The bulk of the HeLa cells treated with BSA-CuS nanoparticles under laser irradiation (808 nm) were killed, and the tumor tissues of mice were also successfully eliminated without causing any obvious systemic damage. In summary, a novel strategy for the synthesis of CuS nanoparticles was developed using BSA as the template, and the excellent biocompatibility and efficient photothermal therapy effects of BSA-CuS nanoparticles show great potential as an ideal photothermal agent for cancer treatment.
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Cobre/química , Cobre/uso terapéutico , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias/terapia , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/uso terapéutico , Animales , Bovinos , Cobre/toxicidad , Células HeLa , Humanos , Hipotermia Inducida , Ratones , Modelos Moleculares , Nanopartículas/toxicidad , Nanotecnología , Neoplasias/patología , Fototerapia , Albúmina Sérica Bovina/toxicidadRESUMEN
Fms-like tyrosine kinase 3 ligand (Flt3L) is known as the primary differentiation and survival factor for dendritic cells (DCs). Furthermore, Flt3L is involved in the homeostatic feedback loop between DCs and regulatory T cell (Treg). We have previously shown that Flt3L accumulates in the synovial fluid in rheumatoid arthritis (RA) and that local exposure to Flt3L aggravates arthritis in mice, suggesting a possible involvement in RA pathogenesis. In the present study we investigated the role of Flt3L on DC populations, Tregs as well as inflammatory responses in experimental antigen-induced arthritis. Arthritis was induced in mBSA-immunized mice by local knee injection of mBSA and Flt3L was provided by daily intraperitoneal injections. Flow cytometry analysis of spleen and lymph nodes revealed an increased formation of DCs and subsequently Tregs in mice treated with Flt3L. Flt3L-treatment was also associated with a reduced production of mBSA specific antibodies and reduced levels of the pro-inflammatory cytokines IL-6 and TNF-α. Morphological evaluation of mBSA injected joints revealed reduced joint destruction in Flt3L treated mice. The role of DCs in mBSA arthritis was further challenged in an adoptive transfer experiment. Transfer of DCs in combination with T-cells from mBSA immunized mice, predisposed naïve recipients for arthritis and production of mBSA specific antibodies. We provide experimental evidence that Flt3L has potent immunoregulatory properties. Flt3L facilitates formation of Treg cells and by this mechanism reduces severity of antigen-induced arthritis in mice. We suggest that high systemic levels of Flt3L have potential to modulate autoreactivity and autoimmunity.
Asunto(s)
Artritis/metabolismo , Enfermedades Autoinmunes/metabolismo , Proteínas de la Membrana/metabolismo , Linfocitos T Reguladores/metabolismo , Animales , Artritis/inducido químicamente , Enfermedades Autoinmunes/inducido químicamente , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/patología , Humanos , Interleucina-6/inmunología , Interleucina-6/metabolismo , Proteínas de la Membrana/genética , Ratones , Albúmina Sérica Bovina/toxicidad , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Tirosina Quinasa 3 Similar a fms/metabolismoRESUMEN
Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly targets the synovial membrane, cartilage and bone. It affects 1 % of the population and is associated with significant morbidity and increased mortality. Se is an essential trace element with antioxidant properties and the ability to modulate the immune responses. Selemax® is an inactive yeast (Saccharomyces cerevisiae) enriched with organic Se. The aim of the present study was to investigate the effects of Selemax® administration in models of an antigen-induced arthritis (AIA) in C57BL/6 mice, and of an adjuvant-induced arthritis (AdIA) in Holtzman rats. As control, the animals were treated with the same inactivated yeast species that was not enriched for Se. In the AIA model, treatment with different doses of Selemax® (0·01, 0·1, 1 and 10 % added to food) significantly decreased the number of inflammatory cells recruited to the knee cavity, essentially by reducing the number of neutrophils. Levels of proinflammatory cytokines, including TNF-α, IL-1ß and chemokine (C-X-C motif) ligand 1/keratinocyte chemoattractant (CXCL1/KC), were also reduced in the peri-articular tissue of mice treated with Selemax® at the tested dose (1 %). In the AdIA model in rats, Selemax® treatment decreased paw oedema and hypernociception. This reduction was associated with inhibition of the influx of proinflammatory cells. Therefore, treatment with Selemax® is associated with amelioration of several inflammatory and functional parameters in models of arthritis, suggesting that this Se-enriched yeast should be evaluated further in patients with RA.
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Artritis/inducido químicamente , Artritis/tratamiento farmacológico , Suplementos Dietéticos , Selenio/administración & dosificación , Selenio/uso terapéutico , Animales , Citocinas/genética , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos/efectos de los fármacos , Masculino , Metaloporfirinas , Ratones , Ratones Endogámicos C57BL , Neutrófilos , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Albúmina Sérica Bovina/toxicidad , LevadurasRESUMEN
UNLABELLED: The therapeutic efficacy of novel designed nonsteroidal anti-inflammatory drug, M2000 (beta- D- mannuronic acid) on experimental immune complex glomerulonephritis was evaluated. Bovine serum albumin (BSA) nephritis was induced in rats by a subcutaneous immunization and daily intravenous administration of BSA. M2000 solution (30 mg/kg) was administered intraperitoneally at regular 48-hr intervals for 4 weeks. Onset of treatment was day 56. Urinary protein was measured weekly and serum anti-BSA antibody was assessed by ELISA method at different intervals. Animals were killed on day 84 and blood samples and kidney specimens were obtained. Serum (creatinine, blood urea nitrogen, cholesterol, and triglyceride) and urine (protein, urea, and creatinine) determinants were measured at the time of sacrifice. Kidney specimens were processed for light and immunofluorescent microscopic examination. The fibrosarcoma cell line was used for assaying tolerability and matrix metalloproteinase type 2 (MMP-2) activity. MMP-2 activity was assessed using zymography. Our data showed that M2000 therapy could significantly reduce the urinary protein excretion in treated rats versus non-treated controls. Anti-BSA antibody titer was lower in treated rats than in controls at the 12th experimental week. Polymorphonuclear neutrophil leukocytes infiltration and glomerular immune complex deposition were less intense in treated rats than in controls. Cytotoxicity analysis of M2000 showed a much higher tolerability compared with other tested drugs (diclofenac, piroxicam and dexamethasone). The inhibitory effect of M2000 in MMP-2 activity was significantly greater than that of dexsamethasone and of piroxicam at a concentration of 200 microg/ml. Moreover, the toxicological study revealed that M2000 had no influence on serum (BUN, creatinine, triglyceride and cholesterol) determinants, urinary protein excretion and glomerular histology in healthy group receiving drug. CONCLUSIONS: These findings suggest that treatment with M2000 can reduce proteinuria, diminish antibody production, and suppress the progression of disease in a rat model of immune complex glomerulonephritis.
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Antiinflamatorios no Esteroideos/farmacología , Glomerulonefritis/tratamiento farmacológico , Ácidos Hexurónicos/farmacología , Animales , Complejo Antígeno-Anticuerpo/metabolismo , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Femenino , Glomerulonefritis/sangre , Glomerulonefritis/inducido químicamente , Glomerulonefritis/patología , Glomerulonefritis/orina , Metaloproteinasa 2 de la Matriz/metabolismo , Proteinuria/sangre , Proteinuria/inducido químicamente , Proteinuria/tratamiento farmacológico , Proteinuria/patología , Proteinuria/orina , Ratas , Ratas Sprague-Dawley , Albúmina Sérica Bovina/toxicidadRESUMEN
OBJECTIVE: To explore the effect of extract of Ginkgo biloba (EGb) on vascular endothelial dysfunction induced by AGEs and to investigate the potential mechanisms. METHODS: Exogenous glycosylated bovine serum Albumin (AGEs-BSA) was prepared according to the methods of article. Vascular endothelial dysfunction was induced by tail vein injection of AGEs-BSA. The treatment group rats were given tail vein injections with AGEs-BSA followed by immediate intragastric of EGb (15,30 mg/kg/day, respectively) for 30 days. At the end of 30 days period, rats were anaesthetized with an intraperitoneal injection of sodium pentobarbital. Blood samples were collected from the carotid artery for biochemical assay of NO, MDA, SOD, DDAH, ADMA. The thoracic aorta was immediately isolated and cut into rings of 3 - 4 mm. Then ACh-induced EDR response and sodium SNP-induced endothelium-independent relaxation of aortic rings were examined. RESULTS: Results from in vivo experiments showed that the injection of AGEs-BSA significantly inhibited ACh-induced EDR response, but had no effect on SNP-induced endothelial-independent relaxation. The injection of AGEs-BSA decreased concentration of serum NO, activity of serum SOD and elevated serum MDA and ADMA level. Egb markedly attenuated AGEs-BSA induced inhibition of EDR response, increase of serum MDA and ADMA level, reduction of both NO level and activity of serum SOD.
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Cardiotónicos/farmacología , Endotelio Vascular/efectos de los fármacos , Ginkgo biloba/química , Extractos Vegetales/farmacología , Acetilcolina/farmacología , Amidohidrolasas/metabolismo , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiología , Cardiotónicos/administración & dosificación , Endotelio Vascular/fisiopatología , Productos Finales de Glicación Avanzada/química , Productos Finales de Glicación Avanzada/toxicidad , Técnicas In Vitro , Masculino , Malondialdehído/sangre , Óxido Nítrico/sangre , Nitroprusiato/farmacología , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/toxicidad , Superóxido Dismutasa/sangre , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaAsunto(s)
Artritis/patología , Resorción Ósea/etiología , Cartílago Articular/patología , Modelos Animales de Enfermedad , Matriz Extracelular/patología , Modelos Animales , Enfermedades Reumáticas , Animales , Antiinflamatorios/uso terapéutico , Artritis/tratamiento farmacológico , Artritis/metabolismo , Artritis/radioterapia , Biomarcadores/análisis , Cartílago Articular/química , Bovinos , Matriz Extracelular/química , Glicosaminoglicanos/análisis , Inmunosupresores/uso terapéutico , Inflamación , Masculino , Metilación , Mycobacterium tuberculosis , Rótula/metabolismo , Rótula/patología , Proteoglicanos/análisis , Ratas , Ratas Endogámicas Lew , Ratas Wistar , Albúmina Sérica Bovina/toxicidad , Especificidad de la Especie , Zimosan/toxicidadRESUMEN
Effects of maternal dietary polyunsaturated fatty acids (PUFA) on the spleen fatty acid composition and BSA-induced wing web swellings were investigated in broilers. One hundred twenty broiler breeder hens 26 wk of age were randomly assigned to diets containing mainly wheat, corn, soy meal, barley, oat and 5% (wt/wt) added sunflower oil, fish oil, or a mix of sunflower and fish oils (1:1). After 2 wk on the experimental diets, birds were inseminated, eggs were collected and incubated. Progeny chicks were then fed identical diets for 6 wk. The maternal dietary oils affected (P < 0.05) n-6 and n-3 PUFA in the spleens of hatching chicks. After 2 wk, n-6 PUFA did not differ among the groups; n-3 PUFA, docosapentaenoic, and docosahexaenoic (DHA) acids were higher (P < 0.05) in the spleens of broilers from hens fed 2.5 or 5% fish oil. After 4 wk, broilers from hens fed 5% fish oil still had higher levels of DHA (P < 0.05) in their spleens than those from hens fed 5% sunflower oil. The BSA-induced wing web swelling response was suppressed (P < 0.05) by n-3 PUFA in breeder hens. Broilers from hens fed high levels of n-3 PUFA had lower (P < 0.05) wing web swelling reactions to BSA at 2 wk (2.5% fish oil) and 4 wk (2.5 and 5% fish oil). In conclusion, n-3 PUFA in breeder hen diets suppressed the BSA-induced wing web swellings of the hens, increased the spleen n-3 fatty acids (especially DHA), and decreased BSA-induced wing web swellings of progeny up to 4 wk of age.
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Pollos/metabolismo , Ácidos Grasos Omega-3/farmacología , Bazo/metabolismo , Análisis de Varianza , Alimentación Animal , Animales , Bovinos , Pollos/inmunología , Dieta/veterinaria , Grasas Insaturadas en la Dieta/administración & dosificación , Grasas Insaturadas en la Dieta/farmacología , Ácidos Docosahexaenoicos/análisis , Ácido Eicosapentaenoico/análisis , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/análisis , Aceites de Pescado , Aceites de Plantas , Distribución Aleatoria , Albúmina Sérica Bovina/inmunología , Albúmina Sérica Bovina/toxicidad , Bazo/química , Bazo/inmunología , Aceite de Girasol , Alas de Animales/efectos de los fármacos , Alas de Animales/patologíaRESUMEN
Bovine serum albumin (BSA) and carminomycin, an anthracycline antibiotic, were subjected to conjugation with glutaraldehyde and their complexes with various contents of the antibiotic were prepared. The molar ratios of carminomycin and BSA were 8:1, 4:1, and 2:1. The antitumor effect of the preparations was studied on the models of mouse transplantable lymphosarcoma LIO equal 1 and ascitic forms of mouse lymphadenosis NK/Ly in vivo and in vitro. Their immunodepressant effect was evaluated from the decrease in the hemagglutinin titers in the mice immunized with sheep red blood cells. It was shown that when the toxicity of the complexes was the same, their antitumor and immunodepressant activities were different. The therapeutic activity of carminomycin in the four- and eight-substituted complexes was much higher than that of carminomycin alone. It is suggested that the differences in the activity of the complexes were connected with differences in their pharmacokinetics. It was found that the chemotherapeutic properties of the complexes may have changed by variation of the number of the cytostatic residues in the albumin molecule. The findings indicate that the whole complex molecule interacts with the malignant cell and not carminomycin preliminarily detached from it.
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Antibióticos Antineoplásicos , Carubicina/uso terapéutico , Daunorrubicina/análogos & derivados , Albúmina Sérica Bovina/uso terapéutico , Animales , Formación de Anticuerpos/efectos de los fármacos , Carubicina/inmunología , Carubicina/toxicidad , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Técnicas In Vitro , Dosificación Letal Mediana , Linfoma/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Ratones , Neoplasias Experimentales/tratamiento farmacológico , Albúmina Sérica Bovina/inmunología , Albúmina Sérica Bovina/toxicidad , Factores de TiempoRESUMEN
Carminomycin was shown to inhibit the development of both the DNA-containing variolovaccine virus and the RNA-containing grippe virus in chick embryos. Comparison of the effects of rubomycin, carminomycin, 14-oxy-carminomycin and carminomycin complex with bovine serum albumin in experiments with chick embryos showed that the inhibitory effect of carminomycin and its derivatives on the development of the grippe virus was much higher than that of rubomycin. The carminomycin derivatives proved to be much more active in this respect than the initial antibiotic. Carminomycin and its derivatives had a therapeutic effect on mice with experimental grippe pneumonia also on their oral use.
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Antibióticos Antineoplásicos/farmacología , Antivirales , Carubicina/farmacología , Animales , Carubicina/análogos & derivados , Carubicina/uso terapéutico , Carubicina/toxicidad , Bovinos , Embrión de Pollo , Daunorrubicina/farmacología , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Virus de la Influenza A/efectos de los fármacos , Dosificación Letal Mediana , Ratones , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Albúmina Sérica Bovina/farmacología , Albúmina Sérica Bovina/uso terapéutico , Albúmina Sérica Bovina/toxicidad , Virus de la Viruela/efectos de los fármacosRESUMEN
The properties of carminomycin complexes with protein, a bovine serum albumin prepared with two different methods using glutaraldehyde or carbodiimine were studied. The complex prepared with the use of carbodiimine was biologically inactive. The complex prepared with the use of glutaraldehyde had a molecular mass of about 15 000 000 dalton, was more toxic than carminomycin and possessed proportionally higher antitumor activity and a wider antitumor spectrum. The studies on the use of the method of carminomycin complex formation with antitumor immunoglobulins are promising.