RESUMEN
Context: HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia japonica Miyabe (Paeoniaceae) developed for immune regulation. HemoHIM has been investigated for its ability to enhance tissue self-renewal and stimulate immune systems. To date, studies on the protective effects of HemoHIM against gastritis and gastric ulcers have not been conducted. Objective: The protective effects of HemoHIM using models of indomethacin and ethanol/hydrochloric acid (EtOH/HCl)-induced gastric mucosal injury were investigated. Materials and methods: Rats were divided into five groups (n = 10): control, indomethacin, or EtOH/HCl groups, HemoHIM 250, 500 mg kg-1, and cimetidine 100 mg kg-1, respectively. Indomethacin (80 mg kg-1) and 60% EtOH/150 mM HCl were administered orally 1 h after the administration of samples and rats were anesthetized 3 h after induction. The lesion area (%), inhibition ratio (%), and total acidity were investigated, and tissues were histopathologically analyzed using hematoxylin and-eosin (H&E) staining. Results: HemoHIM significantly reduced gastric injury in indomethacin-induced model (250 and 500 mg kg-1; 64.30% and 67.75%, p < 0.001) compared to indomethacin group. In the EtOH/HCl-induced model, HemoHIM reduced gastric lesion (250 and 500 mg kg-1; 61.05% and 73.37%, p < 0.001) and gastric acidity (250 and 500 mg kg-1; 37.80 and 45.20 meq L-1, p < 0.001) compared to EtOH/HCl group. H&E staining of the gastric mucosa showed decreased erosion and hemorrhage in HemoHIM group compared to EtOH/HCl group. Discussion and conclusions: Based on the results, HemoHIM is potential candidate for the treatment of gastritis and gastric ulcers.
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Extractos Vegetales/uso terapéutico , Úlcera Gástrica/prevención & control , Animales , Antiulcerosos , Etanol , Mucosa Gástrica , Ácido Clorhídrico , Indometacina , Masculino , Fitoterapia , Ratas Sprague-Dawley , Úlcera Gástrica/inducido químicamenteRESUMEN
Cranial irradiation can trigger adverse effects on brain functions, including cognitive ability. However, the cellular and molecular mechanisms underlying radiation-induced cognitive impairments remain still unknown. Immediate-early genes (IEGs) are implicated in neuronal plasticity and the related functions (i.e., memory formation) in the hippocampus. The present study quantitatively assessed changes in the mRNA and protein levels of the learning-induced IEGs, including Arc, c-fos, and zif268, in the mouse hippocampus after cranial irradiation using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. Mice (male, 8-week-old C57BL/6) received whole-brain irradiation with 0 or 10Gy of gamma-ray and, 2weeks later, contextual fear conditioning (CFC) was used to induce IEGs. In the CFC task, mice evaluated 2weeks after irradiation exhibited significant memory deficits compared with sham (0Gy)-irradiated controls. The levels of mRNA encoding IEGs were significantly upregulated in the hippocampus 10 and 30min after CFC training. The mRNA levels in the irradiated hippocampi were significantly lower than those in the sham-irradiated controls. The IEG protein levels were significantly increased in all hippocampal regions, including the hippocampal dentate gyrus, cornu ammonis (CA)1, and CA3, after CFC training. The CFC-induced upregulation of Arc and c-fos in 10Gy-irradiated hippocampi was significantly lower than that in sham-irradiated controls, although there were no significant differences in the protein levels of the learning-induced zif268 between sham-irradiated and 10Gy-irradiated hippocampi. Thus, cranial irradiation with 10Gy of gamma-ray impairs the induction of hippocampal IEGs (particularly Arc and c-fos) via behavioral contextual fear memory, and this disturbance may be associated with the memory deficits evident in mice after cranial irradiation, possibly through the dysregulation of neuronal plasticity during memory formation.
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Irradiación Craneana/efectos adversos , Miedo/fisiología , Genes Inmediatos-Precoces/fisiología , Hipocampo/metabolismo , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Animales , Conducta Animal/fisiología , Condicionamiento Clásico/fisiología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: HemoHIM, which is an herbal preparation of three edible herbs (Angelicam gigas Nakai, Cnidium offinale Makino, and Peaonia japonica Miyabe), is known to have various biological and immunological activities, but the modulatory effects of this preparation on dendritic cells (DCs)-mediated immune responses have not been examined previously. DCs are a unique group of white blood cells that initiate primary immune responses by capturing, processing, and presenting antigens to T cells. RESULTS: In the present study, we investigated the effect of HemoHIM on the functional and phenotypic maturation of murine bone marrow-derived dendritic cells (BMDCs) both in vitro and in vivo. The expression of co-stimulatory molecules (CD40, CD80, CD86, MHC I, and MHC II) and the production of cytokines (IL-1ß, IL-6, IL-12p70, and TNF-α) were increased by HemoHIM in BMDCs. Furthermore, the antigen-uptake ability of BMDCs was decreased by HemoHIM, and the antigen-presenting ability of HemoHIM-treated mature BMDCs increased TLR4-dependent CD4(+) and CD8(+) T cell responses. CONCLUSIONS: Our findings demonstrated that HemoHIM induces TLR4-mediated BMDCs functional and phenotypic maturation through in vivo and in vitro. And our study showed the antigen-presenting ability that HemoHIM-treated mature BMDCs increase CD4(+) and CD8(+) T cell responses by in vitro. These results suggest that HemoHIM has the potential to mediate DC immune responses.
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Células de la Médula Ósea/efectos de los fármacos , Células Dendríticas/efectos de los fármacos , Extractos Vegetales/farmacología , Receptor Toll-Like 4/metabolismo , Animales , Presentación de Antígeno , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular , Células Dendríticas/citología , Células Dendríticas/metabolismo , Femenino , Activación de Linfocitos , Masculino , Ratones Endogámicos BALB C , Extractos Vegetales/toxicidadRESUMEN
The brain can be exposed to ionizing radiation in various ways, and such irradiation can trigger adverse effects, particularly on learning and memory. However, the precise mechanisms of cognitive impairments induced by cranial irradiation remain unknown. In the hippocampus, brain-derived neurotrophic factor (BDNF) plays roles in neurogenesis, neuronal survival, neuronal differentiation, and synaptic plasticity. The significance of BDNF transcript variants in these contexts is becoming clearer. In the present study, both object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice were assessed 1 month after a single exposure to cranial irradiation (10 Gy) to evaluate hippocampus-related behavioral dysfunction following such irradiation. Furthermore, changes in the levels of BDNF, the cAMP-response element binding protein (CREB) phosphorylation, and BDNF transcript variants were measured in the hippocampus 1 month after cranial irradiation. On object recognition memory and contextual fear conditioning tasks, mice evaluated 1 month after irradiation exhibited significant memory deficits compared to sham-irradiated controls, but no apparent change was evident in locomotor activity. Both phosphorylated CREB and BDNF protein levels were significantly downregulated after irradiation of the hippocampus. Moreover, the levels of mRNAs encoding common BDNF transcripts, and exons IIC, III, IV, VII, VIII, and IXA, were significantly downregulated after irradiation. The reductions in CREB phosphorylation and BDNF expression induced by differential regulation of BDNF hippocampal exon transcripts may be associated with the memory deficits evident in mice after cranial irradiation.
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Factor Neurotrófico Derivado del Encéfalo/efectos de la radiación , Condicionamiento Clásico/efectos de la radiación , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/efectos de la radiación , Hipocampo/efectos de la radiación , Reconocimiento en Psicología/efectos de la radiación , Animales , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Condicionamiento Clásico/fisiología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Miedo/fisiología , Miedo/efectos de la radiación , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Actividad Motora/efectos de la radiación , Fosforilación , ARN Mensajero/metabolismo , ARN Mensajero/efectos de la radiación , Reconocimiento en Psicología/fisiología , Transducción de Señal/efectos de la radiaciónRESUMEN
We examined the effect of HemoHIM on the protective efficacy of hematopoietic stem cells and on the recovery of immune cells against sublethal doses of ionizing radiation. Two-month-old mice were exposed to γ-rays at a dose of 8, 6.5, or 5 Gy for a30-day survival study, endogenous spleen colony formation, or other experiments, respectively. HemoHIM was injected intraperitoneally before and after irradiation. Our results showed that HemoHIM significantly decreased the mortality of sublethally irradiated mice. The HemoHIM administration decreased the apoptosis of bone marrow cells in irradiated mice. On the other hand, HemoHIM increased the formation of endogenous spleen colony in irradiated mice. In irradiated mice, the recovery of total leukocytes in the peripheral blood and lymphocytes in the spleen were enhanced significantly by HemoHIM. Moreover, the function of B cells, T cells, and NK cells regenerated in irradiated mice were significantly improved by the administration of HemoHIM. HemoHIM showed an ideal radioprotector for protecting hematopoietic stem cells and for accelerating the recovery of immune cells. We propose HemoHIM as a beneficial supplement drug during radiotherapy to alleviate adverse radiation-induced effects for cancer patients.
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Linfocitos B/efectos de los fármacos , Rayos gamma/efectos adversos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de la radiación , Células Asesinas Naturales/efectos de los fármacos , Extractos Vegetales/farmacología , Linfocitos T/efectos de los fármacos , Animales , Apoptosis , Linfocitos B/inmunología , Linfocitos B/efectos de la radiación , Femenino , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de la radiación , Prueba de Cultivo Mixto de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Protectores contra Radiación/farmacología , Bazo/citología , Bazo/efectos de la radiación , Linfocitos T/inmunología , Linfocitos T/efectos de la radiación , Irradiación Corporal Total/efectos adversosRESUMEN
OBJECTIVE: In our previous study, repeated irradiations showed persistent depression of immune response, especially Th1-related immune response. Here, we hypothesized and determined that irradiation may exacerbate development of allergic airway inflammation. METHODS: C57BL/6 mice were irradiated repeatedly at 1 Gy or 0.5 Gy. At 6 months after irradiation, mice were sensitized and challenged short-term with OVA. Antigen-specific immunoglobulins, the percentages of inflammatory cells, chemokine expression, cytokine levels, and collagen deposition were tested. RESULTS: In irradiated mice, IgG2a in serum was lower when compared with that of control mice, while IgG1 was significantly higher. Interestingly, the percentages of macrophages in bronchoalveolar lavage fluid (BALF) and the lung of irradiated mice were significantly higher. Conversely, the percentages of neutrophil were significantly lower in BALF of irradiated mice. In the lung of irradiated mice, MCP-1 and IP-10 for attraction of macrophages showed the higher expression level, but KC expression for neutrophils showed no difference. Next, TGF-ß1 and IL-17A in BALF were higher in irradiated mice. In addition, phosphorylated-Smad2/3 was increased in irradiated mice. Finally, the deposition of collagen was increased in irradiated mice. CONCLUSION: Our study showed that fractionated irradiation lead to the chronic allergic airway inflammation through increasing the influx of macrophages and active TGF-ß levels.
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Asma/etiología , Fraccionamiento de la Dosis de Radiación , Macrófagos/efectos de la radiación , Animales , Enfermedad Crónica , Colágeno/metabolismo , Femenino , Inmunoglobulina E/biosíntesis , Inmunoglobulina G/biosíntesis , Interferón gamma/análisis , Interleucina-17/análisis , Interleucina-4/análisis , Macrófagos/fisiología , Ratones , Ratones Endogámicos C57BL , Factor de Crecimiento Transformador beta1/fisiologíaRESUMEN
Cimicifugae rhizoma might be protective against osteoporosis. This study investigated the effects of Cimicifuga heracleifolia (CH), an Asian species of Cimicifugae rhizome, on bone loss in ovariectomized (OVX) mice. The C3H/HeN mice were divided into sham and OVX groups. The OVX mice were treated with vehicle, 17ß-estradiol (E(2) ) or CH for 6 weeks. Serum calcium, phosphorus, E(2) concentration and serum alkaline phosphatase (ALP) activity were measured. Tibiae and femora were analysed using microcomputed tomography. The biomechanical property and osteoclast surface level were measured. Treatment with CH (i.p., 50 mg/kg of body weight, every other day) prevented the OVX-induced increase in body weight but did not alter the uterus weight of the OVX mice. Serum ALP levels and osteoclast surface levels in the OVX mice were reduced by treatment with CH. The CH significantly preserved trabecular bone mass, bone volume, trabecular number, trabecular thickness, structure model index and bone mineral density of proximal tibia metaphysis or distal femur metaphysis. However, grip strength, mechanical property and cortical bone architecture did not differ among the experimental groups. The results indicate that the supply of CH can prevent OVX-induced bone loss in mice.
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Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Cimicifuga/química , Medicamentos Herbarios Chinos/farmacología , Osteoporosis/tratamiento farmacológico , Rizoma/química , Animales , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/prevención & control , Huesos/diagnóstico por imagen , Calcio/sangre , Medicamentos Herbarios Chinos/aislamiento & purificación , Estradiol/sangre , Femenino , Ratones , Ratones Endogámicos C3H , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis/sangre , Osteoporosis/diagnóstico por imagen , Ovariectomía/efectos adversos , Plantas Medicinales/química , Distribución Aleatoria , Organismos Libres de Patógenos Específicos , Aumento de Peso/efectos de los fármacos , Microtomografía por Rayos XRESUMEN
Globally, one in three of the World's adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO) estimates the number of chubby adults will balloon to 2.3 billion--Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl gallate from the herbal composition known as HemoHIM that actively inhibits lipid formation as evidenced by Oil Red O staining and triglyceride (TG) contents in 3T3-L1 adipocytes, suggesting their use as an anti-obesity agent. Furthermore, the amount of glycerol released from cells into the medium had increased by treatment of methyl gallate in a concentration-dependent manner. The present study suggests that a promising anti-obesity agent like methyl gallate might be of therapeutic interest for the treatment of obesity.
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Fármacos Antiobesidad/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Adipocitos/efectos de los fármacos , Animales , Fármacos Antiobesidad/química , Fármacos Antiobesidad/toxicidad , Línea Celular , Evaluación Preclínica de Medicamentos , Lipólisis/efectos de los fármacos , Ratones , Extractos Vegetales/química , Extractos Vegetales/toxicidadRESUMEN
Although one of the several chronic effects of ionizing radiation is aging, there are no experimental data on radiation-induced immunological aging. The most interesting change in aging was a helper T (Th) 1/Th2 imbalance. We investigated chronic effect on immune responses after ionizing radiation and its effects in irradiated mice were compared with those of aged mice. The 2-month-old mice received a whole-body irradiation of 5Gy. At 6months after irradiation, we compared the immune functions of the irradiated mice with those of normal mice of the same age and with those of older. Interferon (IFN)-γ and antigen-specific immunoglobulin (Ig)G2a level were lower in the irradiated mice than in normal mice of same age, showing similar levels to those of old normal mice. In contrast, interleukin (IL)-4 and IL-5 and antigen-specific IgG1 level were increased in irradiated mice when compared with the same aged-normal mice. Next, we investigated the low expression of IL-12p70, IL-12 receptors and IL-18 receptors in irradiated and old mice. Also, the decrease of natural killer cell activity was intensified in the irradiated mice, showing lower than values to those of old mice. Interestingly, in irradiated mice, the absolute numbers and the percentages of natural killer (NK) cells was extremely decreased. But the absolute numbers of Th cells and cytotoxic T (Tc) cells in old mice were significantly decreased. In conclusion, an immunological imbalance by the whole-body irradiation of 5Gy induces to persist in the long term, resulting in the similar results with aging. Our results suggest that the downregulation of the Th1-like immune response shown in old mice rapidly occurred through exposure of ionizing radiation.
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Envejecimiento/fisiología , Rayos gamma , Células TH1/inmunología , Células TH1/efectos de la radiación , Animales , Línea Celular Tumoral , Proliferación Celular , Femenino , Ratones , Ratones Endogámicos C57BL , Células TH1/citologíaRESUMEN
Globally, over 170 million people (ca. 3% of the World's population) are infected with the hepatitis C virus (HCV), which can cause serious liver diseases such as chronic hepatitis, evolving into subsequent health problems. Driven by the need to detect the presence of HCV, as an essential factor in diagnostic medicine, the monitoring of viral protein has been of great interest in developing simple and reliable HCV detection methods. Despite considerable advances in viral protein detection as an HCV disease marker, the current enzyme linked immunosorbent assay (ELISA) based detection methods using antibody treatment have several drawbacks. To overcome this bottleneck, an RNA aptamer become to be emerged as an antibody substitute in the application of biosensor for detection of viral protein. In this study, we demonstrated a streptavidin-biotin conjugation method, namely, the RNA aptamer sensor system that can quantify viral protein with detection level of 700 pg mL(-1) using a biotinylated RNA oligonucleotide on an Octet optical biosensor. Also, we showed this method can be used to screen inhibitors of viral protein rapidly and simply on a biotinylated RNA oligonucleotide biosensor. Among the inhibitors screened, (-)-Epigallocatechin gallate showed high binding inhibition effect on HCV NS5B viral protein. The proposed method can be considered a real-time monitoring method for inhibitor screening of HCV viral protein and is expected to be applicable to other types of diseases.
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Aptámeros de Nucleótidos/química , Hepacivirus/aislamiento & purificación , Hepatitis C/diagnóstico , Proteínas no Estructurales Virales/análisis , Antivirales/química , Antivirales/farmacología , Biotina/química , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Sistemas de Computación , Humanos , Estreptavidina/química , Proteínas no Estructurales Virales/antagonistas & inhibidoresRESUMEN
BACKGROUND: Globally, severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emerging virus that causes SARS with high mortality rate in infected people. The nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is an important antigen for the early diagnosis of SARS and the detection of diseases. Here, a new quantum dots (QDs)-conjugated RNA aptamer with high sensitivity and rapidity is proposed for the detection of SARS-CoV N protein using an on chip system. RESULTS: A QDs-conjugated RNA aptamer can specifically hybridize on the immobilized SARS-CoV N protein on the surface of a glass chip. Detection is based on the optical signal variation of a QDs-supported RNA aptamer interacting on an immobilized protein chip. Using an optical QDs-based RNA aptamer chip, SARS N protein was detected at concentrations as low as 0.1 pg mL-1. CONCLUSIONS: It was demonstrated that the QDs-conjugated RNA aptamer could interact on a designed chip specifically and sensitively. This device could form a QDs-conjugated biosensor prototype chip for SARS-CoV N protein diagnosis. The proposed visual SARS-CoV N protein detection technique may avoid the limitations of other reported methods because of its high sensitivity, good specificity, ease of use, and the ability to perform one-spot monitoring. Copyright © 2011 Society of Chemical Industry.
RESUMEN
Globally, there are concerns over the risks associated with radiation exposure, so it is important to understand the biological effects of radiation exposure. Driven by the need to detect the presence of radiation exposure, biomarkers to monitor potential exposure after radiological accidents can be developed and would be extremely valuable for biological response. In this study, the behavior of spermidine as a biomarker was investigated in a C57BL/6 mouse model exposed to an acute whole-body sublethal dose of 6 Gy. The spermidine content values in serum increased for up to two days after 6 Gy irradiation. However, the enhanced spermidine content observed on day +3 in irradiated mice returned to normal levels on the subsequent five days. The result indicates that spermidine can be used as a biomarker of biological response to radiation exposure.
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Rayos gamma , Espermidina/sangre , Animales , Biomarcadores/sangre , Calibración , Cromatografía Líquida de Alta Presión/normas , Ingestión de Alimentos/efectos de la radiación , Femenino , Ratones , Ratones Endogámicos C57BL , Estándares de Referencia , Pérdida de Peso/efectos de la radiaciónRESUMEN
BACKGROUND/AIM: Although cisplatin is an effective anticancer drug, its toxic effects on normal tissues limit its use. We developed a herbal formula, MH-30, with increased fat-soluble polyphenols by improving the manufacturing method of HemoHIM. In this study, we examined whether the combination of MH-30 with cisplatin exerts synergistic antitumor effect while it reduces cisplatin-induced toxicities. MATERIALS AND METHODS: MH-30 was produced by adding the ethanol-insoluble fraction to its extract after decocting herbs in 30% ethanol and water. We used a melanoma-bearing mice model to investigate synergistic anticancer effects. The NK cell activity and cytokine levels were measured by Cr51-release assay and ELISA. The AST, ALT, BUN, and creatinine levels were estimated in the serum. RESULTS: MH-30 effectively inhibited melanoma growth in vitro. Furthermore, MH-30 had a synergistic effect in combination with cisplatin on melanoma growth inhibition in vitro and in vivo. In melanoma-bearing mice, cisplatin alone decreased the activity of NK cells and the levels of IL-2 and IFN-γ, which were effectively restored by the combination of MH-30 with cisplatin. Combined treatment with MH-30 and cisplatin significantly inhibited the cisplatin-induced increase in the levels of AST, ALT, BUN, and creatinine. CONCLUSION: Combination of MH-30 with cisplatin may be a beneficial anticancer treatment with reduced adverse effects.
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Antineoplásicos , Melanoma , Animales , Antineoplásicos/farmacología , Cisplatino , Células Asesinas Naturales , Melanoma/tratamiento farmacológico , RatonesRESUMEN
BACKGROUND: Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. METHODS: HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. RESULTS: In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. CONCLUSION: HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma Experimental/tratamiento farmacológico , Angelica/química , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Cnidium/química , Citotoxicidad Inmunológica/efectos de los fármacos , Sinergismo Farmacológico , Ensayo de Inmunoadsorción Enzimática , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Mitomicina/administración & dosificación , Paeonia/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Resultado del TratamientoRESUMEN
To evaluate the ability of red ginseng (RG) to protect the skin from photodamage, the gross and microscopic changes in the skin of hairless mice and RG-treated mice exposed chronically to UV were examined. The skin of the UV-irradiated mice showed characteristic signs of photoaging, such as deep wrinkles across the back, increased epidermal thickness, numerous cell infiltration, and many enlarged keratinizing cysts. The RG-treated mice showed a significantly decreased wrinkling score, minimal epidermal hyperplasia, slightly increased dermal cellularity and lack of proliferation of cysts. By week 22, 88.9% (i.p. with saline) or 60.0% (topical administration with cream base) of the UV-irradiated mice developed at least one tumor. RG delayed tumor onset significantly. RG was also effective in reducing the occurrence of UV radiation-induced skin tumors and reduced the number of tumors per mouse. After 22 weeks of treatment, 57.1% (i.p.) or 85.7% (topical administration) of the mice treated with RG were tumor-free. Tumor multiplicity was reduced by 89.3% (i.p.) or 92.2% (topical administration) in the RG treated groups. It is noted that skin that is chronically exposed to UV is subject to photoaging and photocarcinogenesis and the regular use of RG would prevent these photodamaging effects of UV.
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Panax/química , Extractos Vegetales/uso terapéutico , Envejecimiento de la Piel , Piel/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Administración Cutánea , Animales , Femenino , Ratones , Ratones Pelados , Neoplasias Inducidas por Radiación/patología , Traumatismos Experimentales por Radiación/patología , Protectores contra Radiación/uso terapéutico , Piel/patología , Piel/efectos de la radiación , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/prevención & controlRESUMEN
BACKGROUND/AIM: Ionizing radiation induces pulmonary fibrosis, which is a common dose-limiting complication in patients receiving radiotherapy. Fibrosis occurs through the accumulation of large amounts of ECM components, synthesized by myofibroblasts in damaged lung tissue. Epithelial cells serve as one of the cellular sources of myofibroblasts via the epithelial-to-mesenchymal transition (EMT) process. In this study, we investigated the role of TGF-ß-secreting M2 macrophages in association with ionizing radiation-induced EMT. MATERIALS AND METHODS: The lung epithelial cell line MLE12, was irradiated and the expression of EMT markers and chemokines was examined. Moreover, the mouse lung macrophage MH-S cell line was cultured with conditioned media from irradiated MLE12 cells, to examine the effects of the secreted factors on the migration ability of macrophages. For the murine pulmonary fibrosis model, mice were locally irradiated and the levels of M1 or M2 macrophage-related markers and cytokines were measured in bronchoalvelolar lavage (BAL) fluid and lung tissue. RESULTS: In MLE12 cells, irradiation directly induced expression of EMT-related markers and secretion of various chemokines, which lead to macrophage migration. Interestingly, the sub-population of macrophages recruited in the lung of mice after thoracic irradiation was M2 macrophages that expressed Arg-1 and CD206. M2 macrophages induced the MLE12 to undergo phenotypic conversion to form fibroblast-like cells, which leads to a down-regulation of epithelial markers and an up-regulation of new EMT-related markers. In thoracic irradiated mice, pro-inflammatory cytokines such as IL-1ß, IL-4 and IL-10 were increased at 2 weeks, but returned to normal levels from 16 weeks or 24 weeks after irradiation. However, thoracic irradiation led to a rapid increase of TGF-ß and IGF-1 levels, which lasted up to 24 weeks. It was confirmed that M2 macrophages secreted the high levels of TGF-ß. Moreover, the elimination of TGF-ß from M2 macrophages attenuated mesenchymal transition of MLE12. CONCLUSION: TGF-ß-secreting M2 macrophages play an important regulatory role in mesenchymal transition of epithelial cells in the lung of irradiated mice, thus contributing to radiation-induced pulmonary fibrosis.
Asunto(s)
Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/efectos de la radiación , Pulmón/metabolismo , Macrófagos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Línea Celular , Citocinas/metabolismo , Células Epiteliales/efectos de la radiación , Femenino , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Pulmón/efectos de la radiación , Macrófagos/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Neumonitis por Radiación/etiología , Neumonitis por Radiación/metabolismo , Radiación Ionizante , Transducción de Señal/efectos de la radiaciónRESUMEN
BACKGROUND: Although there are some reports on neutron teratology, there is little information on the adaptive response of gamma radiation for protection against neutron-induced teratogenesis. This study examined whether or not a low dose of gamma radiation can induce an adaptive response in mouse fetuses exposed to a subsequent dose of neutrons in vivo. METHODS: Pregnant ICR mice were exposed to a priming dose of 0.3 Gy (0.9 Gy/min) of gamma rays on day 10.5 of gestation and challenged with 0.8 Gy (0.94 Gy/minute) of neutrons 24 h later. The mice were sacrificed on day 18.5 of gestation. The fetuses were examined for mortality, growth retardation, and other morphologic abnormalities. RESULTS: The tail length in the 0.3 Gy of gamma rays + 0.8 Gy of neutrons group was significantly shorter than in the 0.8 Gy of neutrons group. Although there was no significant difference compared with the 0.8 Gy of neutrons group, the number of live fetuses in the 0.3 Gy of gamma rays +0.8 Gy of neutrons group was lower. There was no evidence of primed exposure-related reductions in the malformed fetuses. Although there was no significant difference compared with the unprimed group, the number of malformed offspring in the primed group was higher. Furthermore, the incidence of kinked tail and adactyly was significantly higher in the primed mice than in the unprimed mice. CONCLUSIONS: Overall, this study shows that exposure to 0.3 Gy of gamma rays failed to induce an adaptive response of fetogenesis to a neutron challenge dose.
Asunto(s)
Anomalías Inducidas por Radiación/etiología , Feto/efectos de la radiación , Rayos gamma , Neutrones/efectos adversos , Efectos Tardíos de la Exposición Prenatal/mortalidad , Protección Radiológica , Animales , Relación Dosis-Respuesta en la Radiación , Femenino , Ratones , Ratones Endogámicos ICR , Embarazo , Tolerancia a RadiaciónRESUMEN
In this study we evaluated the effect of water extracts of green tea (GT) and mixtures of green tea polyphenols (GTPs), epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC) on jejunal crypt survival, endogenous spleen colony formation, and apoptosis in jejunal crypt cells of mice irradiated with gamma-ray. The radioprotective effect of green tea was compared with the effect of diethyldithiocarbamate (DDC). Jejunal crypts were protected by pretreatment of GT and ECG. Administration of GT, GTPs and EC prior to irradiation resulted in an increase in the formation of endogenous spleen colonies. The frequency of apoptosis in crypt cells was also reduced by pretreatment of GT, GTPs, EGCG, ECG and EGC. In the experiment on the effect of catechins, the effects were partly contradicted in irradiated mice. The rank order of activity was ECG > EGC > EGCG > EC on intestinal crypt survival assay, EC > EGC > ECG > EGCG on the spleen colony formation assay, EGCG > EGC > EC > ECG on inhibiting the death of cells caused by apoptosis. The results indicate that GT and GTPs may have a major radioprotective effect. Each one of the catechins was a much less effective radioprotector, suggesting that total extract or a mixture of GTPs may be more effective than individual catechins.
Asunto(s)
Apoptosis/efectos de la radiación , Flavonoides/farmacología , Rayos gamma , Yeyuno/efectos de la radiación , Fenoles/farmacología , Té/química , Animales , Apoptosis/efectos de los fármacos , Femenino , Yeyuno/citología , Yeyuno/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , PolifenolesRESUMEN
In whole-body-irradiated (WBI) mice, levels of the canonical Th1 cytokine IFN-gamma (IFNG) have been shown to be markedly reduced, resulting in a Th1/Th2 imbalance. In this study, the influence of natural killer (NK) cells on the balance of this Th1/Th2 immune response was evaluated in WBI mice. Although NK cells are one of the types of cells that secreteIFN-gamma, NK cell activity tends to be minimal, even at 7 weeks after irradiation. In NK cell-depleted mice, the levels of Th1-related cytokines were lower than those of the control mice and were correlated with lower IgG2a production and elevated IgE and IgG1 production. These results indicated that NK cells have a crucial role in the final differentiation of Th cells into Th1 cells. The impairment of NK cells in the WBI mice was confirmed by the observation that NK cells from the WBI mice induced a decrease in the generation of IFN-gamma by the NK cell-depleted spleen lymphocytes from normal mice. Also, the WBI mice that received NK cells obtained from the normal mice generated more IgG2a, IL12 and IFN-gamma. Our results indicate that the impairment of NK cells is an important factor in the reduced Th1-like response in irradiated mice.
Asunto(s)
Células Asesinas Naturales/efectos de la radiación , Células TH1/efectos de la radiación , Traslado Adoptivo , Animales , Interferón gamma/biosíntesis , Células Asesinas Naturales/inmunología , Ratones , Ratones Endogámicos C57BL , Células TH1/inmunología , Células Th2/inmunología , Células Th2/efectos de la radiaciónRESUMEN
Cytogenetic and hematological analyses were performed on the peripheral blood lymphocytes (PBLs) obtained from Korean native cattle bred in the vicinity of three nuclear power plants (Wolsong, Uljin and Yeonggwang) and in a control area. The micronucleus (MN) rates for the cattle from the Wolsong, Uljin and Yeonggwang nuclear power plants and for the control area were 9.87 +/- 2.64, 8.90 +/- 3.84, 9.20 +/- 3.68 and 9.60 +/- 3.91 per 1,000 cytokinesis-blocked lymphocytes, respectively. The apparent difference is not statistically significant. The MN frequencies of PBLs from cattle bred in the four areas are within the background variation for this study. The MN frequencies and hematological values were similar regardless of whether the cattle were bred near a nuclear power plant or in the control area.