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The objective of this study is to develop hydroxyapatite (HAp) particles for targeted delivery of honokiol to tumor sites after glioma surgical management. Honokiol is released from the HAp-honokiol particles inside cancer cells through endocytosis and subsequent acid lysosomal dissolution. HAp is synthesized using a co-precipitation method, and egg white is added to create porous structures. The HAp is then surface-modified with stearic acid to enhance its hydrophobicity and loaded with honokiol to form HAp-honokiol particles. The synthesized particles are of appropriate size and characteristics for cancer cell uptake. Honokiol remains attached on to the HAp particles in neutral environments due to its hydrophobic nature, but undergoes rapid burst release in acidic environments such as lysosomes. The HAp-honokiol treatment shows a delayed effect on cell viability and cytotoxicity, indicating sustained drug release without compromising drug efficacy. Flow cytometry analysis demonstrates the apoptosis pathway induced by HAp-honokiol in ALTS1C1 glioma cells. In the in vivo study using a mouse glioma model, MRI results showed a 40% reduction in tumor size after HAp-honokiol treatment. These findings suggest that HAp-honokiol particles have potential as an effective drug delivery system for the treatment of glioma.
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Durapatita , Glioma , Humanos , Durapatita/química , Porosidad , Sistemas de Liberación de Medicamentos , Glioma/tratamiento farmacológicoRESUMEN
L-theanine (LT), which is a major amino acid found in green tea, was shown to alleviate Vincristine (VCR)-induced peripheral neuropathy and associated neuronal functional changes in rats. To induce peripheral neuropathy, rats were administered VCR at a dose of 100 mg/kg/day intraperitoneally on days 1-5 and 8-12, while control rats received LT at doses of 30, 100, and 300 mg/kg/day intraperitoneally for 21 days or saline solution. Electrophysiological measurements were taken to evaluate the nerve functional loss and recovery through motor and sensory nerve conduction velocities. The sciatic nerve was examined for several biomarkers, including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total calcium, IL-6, IL-10, MPO, and caspase-3. The results showed that VCR caused significant hyperalgesia and allodynia in rats; decreased nerve conduction velocity; increased NO and MDA levels; and decreased GSH, SOD, CAT, and IL-10 levels. LT was found to significantly reduce VCR-induced nociceptive pain thresholds, decrease oxidative stress levels (NO, MDA), increase antioxidative strength (GSH, SOD, CAT), and reduce neuroinflammatory activity and apoptosis markers (caspase-3). LT's antioxidant, calcium homeostasis, anti-inflammatory, anti-apoptotic, and neuroprotective properties make it a potential adjuvant to conventional treatment in VCR-induced neuropathy in rats.
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Recent years have seen a rapidly rising number of oxygenated water brands that claim to impart health benefits and increase athletic performance by improving oxygen availability in the body. Drinks with higher dissolved oxygen concentrations have in recent times gained popularity as potential ergogenic aids, despite the lack of evidence regarding their efficacy. The aim of this study was to characterize oxygenated water and assess the improvement in uric acid metabolism while identifying performance enhancements in animals administered oxygenated water. Oxygenated water was characterized by hydrogen and oxygen nuclear magnetic resonance (NMR) spectroscopy. Hyperuricemia in rats was induced by treatment with oxonic acid potassium salt, and the animals were given oxygenated drinking water before, during, or after oxonic acid treatment. Serum uric acid was measured to confirm the effects on uric acid metabolism. Following oxygenation, the full width at half maximum (FWHM) was reduced to 11.56 Hz and 64.16 Hz in the hydrogen and oxygen NMR spectra, respectively. Oxygenated water molecule clusters were reduced in size due to the reduction in FWHM. Oxygen concentration did not vary significantly with increased temperature. However, standing time played a critical role in the amount of oxygen dissolved in the water. The rat studies indicated that oxygenated water reduced serum uric acid levels and their rate of increase and enhanced uric acid metabolism. A significant improvement in uric acid metabolism and rate of increase in serum uric acid concentration was observed in hyperuricemic rats administered oxygenated water compared to that in rats administered regular water. High oxygen concentrations enhanced the rate of oxygen absorption, leading to increased glycolysis and mitochondrial protein synthesis. Therefore, oxygenated water is a potential adjuvant therapy or health food for treatment of hyperuricemia.
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Agua Potable , Hiperuricemia/metabolismo , Oxígeno/administración & dosificación , Oxígeno/metabolismo , Animales , Hiperuricemia/sangre , Modelos Animales , RatasRESUMEN
Rotenone (ROT)-induced neurotoxicity has been used for decades as an animal model of Parkinson's disease (PD) in humans. This model exhibits pathophysiological features similar to those reported in patients with PD, namely, striatal nitrosative and oxidative stress, mitochondrial dysfunction, and neural cytoarchitecture alteration. (-)Epigallocatechin-3-gallate (EGCG), the most abundant and potent green tea catechin, has notable anti-oxidative, anti-inflammatory, and neuroprotective effects. The objective of the present study was to investigate the potential protective effects of EGCG on ROT-induced motor and neurochemical dysfunctions in rats. Furthermore, we also aimed to study the neuroprotective mechanisms underlying these effects. ROT treatment (0.5 mg/kg s.c., 21 days) reduced body weight and induced significant motor impairments as assessed using an open-field test, rotarod test, grip strength measurement, and beam-crossing task. EGCG treatment (100 or 300 mg/kg i.p., 60 min prior to ROT administration, 21 days) prevented most of the ROT-induced motor impairments. Moreover, EGCG treatment reduced ROT-induced nitric oxide (NO) level and lipid peroxidation (LPO) production; increased the activity of succinate dehydrogenase (SDH), ATPase, and ETC enzymes and the levels of catecholamines in the striatum; and reduced the levels of neuroinflammatory and apoptotic markers. These results demonstrate the possible neuroprotective effects of EGCG against ROT-induced motor impairments, including anti-oxidatory effect, prevention of mitochondrial dysfunction, prevention of neurochemical deficiency, anti-neuroinflammatory effect, and anti-apoptotic effect. This is the first report about the neuroprotective effect of EGCG against ROT-induced motor impairments, and the above evidence provides a potential clinically relevant role for EGCG in delaying or treating human PD.
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Catequina/análogos & derivados , Cuerpo Estriado/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Trastornos Parkinsonianos/prevención & control , Rotenona/toxicidad , Animales , Apoptosis/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Catequina/administración & dosificación , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Encefalitis/inducido químicamente , Mediadores de Inflamación/metabolismo , Masculino , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/metabolismo , Ratas WistarRESUMEN
BACKGROUND/PURPOSE: Spinal cord injury (SCI) is a devastating medical condition for which no effective pharmacological interventions exist. l-Theanine (LT), a major amino acid component of green tea, exhibits potent antioxidative and anti-inflammatory activities and protects against various neural injuries. Here, we evaluated the potential therapeutic effects of LT on the recovery of behavioral motor functions after SCI in rats and the underlying neuroprotective mechanisms. METHODS: SCI was induced by applying vascular clips to the dura through a four-level T5-T8 laminectomy, and saline or LT (10/30 mg/kg) was intrathecally administered at 1-, 6-, and 24-h post-SCI. At 72-h post-SCI, half of the rats from each group for each parameter were sacrificed, and their spinal cord was excised for measurement of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase, catalase, tumor necrosis factor-α, interleukin-1ß/-6, myeloperoxidase, and caspase-3. The remaining rats from each group were subjected to Bresnahan locomotor-rating scale (BBB), inclined-plane, toe-spread, and hindfoot bar-grab tests at 1-, 4-, 7-, 10-, and 14-days post-SCI. RESULTS: LT treatment reduced NO and MDA levels, increased antioxidative strength, and markedly suppressed the levels of neuroinflammatory and apoptotic markers in the spinal cord after SCI. Moreover, LT treatment drastically promoted the recovery of behavioral motor functions post-SCI. CONCLUSION: Our findings revealed that LT can enhance the recovery of behavioral motor functions after SCI in rats, which related to the suppression of post-traumatic oxidative response, neural inflammation, and apoptosis. This evidence indicates that LT holds considerable potential for use in the clinical treatment/prevention of SCI-induced motor dysfunction.
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Glutamatos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo , Traumatismos de la Médula Espinal , Animales , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Traumatismos de la Médula Espinal/tratamiento farmacológicoRESUMEN
Having powerful antioxidative properties, L-theanine (LT), one of the major amino acid components in green tea, has potent anti-oxidative and neuroprotective effects. In this study, we examined the potential protective effects of LT on haloperidol (HAL)-induced orofacial dyskinesia (OD) in rats. HAL treatment (1 mg/kg intraperitoneally for 21 days) induced OD; significant increases (P < 0.001) in the frequency of vacuous chewing movement and tongue protrusion as well as the duration of facial twitching. LT treatment (100 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of the HAL-induced OD. LT treatment was also able to reduce the lipid peroxidation production and nitric oxide (NO) level, and enhance the antioxidation power in striatum from rats with HAL treatment. In order to examine the implication of NO pathway activity in HAL treatment, either NO precursor (L-arginine) or NO synthase inhibitor (L-NAME) was co-pretreated with LT; NO precursor treatment eliminated the protective effect of LT, in contrast to that NO synthase inhibitor treatment significantly potentiated the LT effects on behavioral and biochemical protection in HAL-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the HAL-induced OD, as well as in the protective effect of LT in treating HAL-induced OD. The above evidence provides a clinically relevant value for LT in delaying or treating tardive dyskinesia.
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Discinesias , Animales , Antipsicóticos , Glutamatos , Haloperidol , Óxido Nítrico , Ratas , Ratas WistarRESUMEN
Exosomes are attractive potential carriers for drug delivery because of their natural function of transferring biomolecules among cells without eliciting immune responses. However, an obstacle to the application of exosomes for drug delivery is the difficulty in collecting sufficient numbers of these vesicles. In this study, we demonstrate treatment with calcium phosphate (CaP) particles could increase over two-fold the number of exosomes secreted from macrophage-like RAW264.7 cells and monocyte-like THP-1 cells. CaP particles were easily internalized into cells and dissolved in acidic late-endosomes or lysosomes, resulting in the rupture of their membranes followed by the release of Ca2+ into cytosol. Moreover, we found that exosomes secreted from cells treated with CaP particles are not contaminated by the Ca2+ released from CaP; the Ca2+ contents in exosomes secreted from CaP particle-treated cells were similar to that in exosomes from untreated control cells. This study highlights the potential for the efficient production of exosomes using CaP particles for drug delivery.
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Fosfatos de Calcio/química , Sistemas de Liberación de Medicamentos , Exosomas/efectos de los fármacos , Fagocitos/efectos de los fármacos , Animales , Línea Celular , Proliferación Celular , Supervivencia Celular , Exosomas/metabolismo , Ratones , Tamaño de la Partícula , Fagocitos/metabolismo , Células RAW 264.7 , Propiedades de SuperficieRESUMEN
Reserpine (RES)-induced orofacial dyskinesia (OD) has been used as an animal model for human tardive dyskinesia (TD) for decades, due to its strong pathophysiological association with striatal oxidative stress and neural cytoarchitecture alteration. L-Theanine (LT), one of the major amino acid components in green tea, has potent antioxidative, anti-inflammatory, and neuroprotective effects. In this study, we examined the potential protective effects of LT on RES-induced behavioral and neurochemical dysfunction in rats. RES treatment (1 mg/kg s.c., 3 injections 1 day apart) induced significant increases (p < 0.001) in the frequency of vacuous chewing movements (VCM), tongue protrusion (TP), as well as the duration of facial twitching (FT). LT treatment (100, 300 mg/kg orally for 14 days, starting 10 days before RES injection) was able to prevent most of the RES-induced OD. Moreover, LT treatment reduced the RES-induced lipid peroxidation (LPO) production, increased the antioxidation power and catecholamines in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results indicated that LT was able to counteract the increased oxidative damage, neurotransmitter deficiency, neuroinflammation, and apoptosis induced by RES, and these results have demonstrated the possible neuroprotective effects of LT against RES-induced OD, including antioxidation, neurochemical deficiency prevention, antineuroinflammation, and antiapoptosis. These findings, therefore, suggest a potential role for LT to have a clinically relevant therapeutic effect in delaying or treating human TD.
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Antipsicóticos/toxicidad , Discinesias/tratamiento farmacológico , Discinesias/etiología , Glutamatos/uso terapéutico , Reserpina/toxicidad , Análisis de Varianza , Animales , Caspasa 3/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Neurotransmisores/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Tardive dyskinesia (TD) is a severe side effect of chronic neuroleptic treatment consisting of abnormal involuntary movements, characterized by orofacial dyskinesia (OD). Haloperidol (HAL)- induced OD has been widely used as an animal model to study the neuropathophysiology of human TD with its pathophysiology strongly associated with striatal oxidative stress. L-Theanine (LT), one of the major amino acid components in green tea, has potent antioxidative effects and is able to protect against various oxidative injuries. In this study, we examined the potential protective effects of LT on HAL-induced behavioral and neurochemical dysfunction in rats. HAL treatment (1 mg/kg i.p. for 21 days) induced significant increases (P < 0.001) in the frequency of vacuous chewing movement (VCM) and tongue protrusion (TP) as well as the duration of facial twitching (FT). LT treatment (100, 300 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of the HAL-induced OD. LT treatment was also able to reduce the lipid peroxidation (LPO) production, and enhance the antioxidation power in striatum from rats with HAL treatment. The above results indicate that LT has a protective role against HAL-induced OD, probably via its powerful antioxidative properties. Thus, LT may have a clinically relevant therapeutic effect in delaying or treating TD.
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Discinesias/prevención & control , Glutamatos/farmacología , Haloperidol/toxicidad , Discinesia Tardía/prevención & control , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Discinesia Tardía/inducido químicamenteRESUMEN
An antidepressant carrier, mesoporous hydroxyapatite olanzapine (mesoHAP-OLZ), was designed to maintain 3weeks of constant medication release. The carrier was intramuscularly (IM) injected, where cellular activity played a role in achieving the goal of constant release. The efficiency of the treatment was evaluated from 3 perspectives in in vivo studies: locomotor activities, biomarkers, and learning and memory ability. MesoHAP-OLZ can increase the locomotor activity in rats with induced depression determined by open field test (OFT) and forced swim test (FST). Serotonin (5-HT), one of the most important biomarker in depression can also be increased by mesoHAP-OLZ, leading to increased hippocampus activity as measured by functional magnetic resonance imaging (fMRI). MesoHAP-OLZ can also improve learning and memory ability in rats with induced depression during Morris water maze (MWM) test. Our findings further show that mesoHAP-OLZ can provide long-term drug release with a single IM injection, helping to solve the problem of non-adherent medication intake that often occurs in antidepressant therapy.
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Benzodiazepinas/administración & dosificación , Depresión/tratamiento farmacológico , Portadores de Fármacos/administración & dosificación , Durapatita/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Animales , Conducta Animal/efectos de los fármacos , Benzodiazepinas/química , Benzodiazepinas/uso terapéutico , Benzodiazepinas/toxicidad , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Depresión/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/uso terapéutico , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Durapatita/química , Durapatita/uso terapéutico , Durapatita/toxicidad , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Olanzapina , Porosidad , Ratas Wistar , Serotonina/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/química , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/toxicidadRESUMEN
Reserpine (RES) has been reported to increase the brain's neural oxidative stress and cause cognitive dysfunction. Having powerful antioxidative properties, green tea catechins, especially (-)epigallocatechin-3-gallate (EGCG), are able to protect against many oxidative injuries. In this study, we examined the protecting properties of EGCG on RES-induced impairment of short-term memory in three-month-old male Wistar rats. RES (1mg/kg i.p.) induced memory impairment (p<0.001) as evaluated by the social recognition task. EGCG treatment (100mg/kg i.p. for 7days, starting 6days before RES injection) was able to improve the impaired memory caused by RES. RES treatment increased the nitric oxide (NO) level and lipid peroxidation (LPO) production, and decreased the antioxidation power in hippocampi. EGCG treatment was able to counteract the RES-induced NO level and LPO production, as well as enhanced the hippocampal antioxidation power in RES-treated rats. In order to examine the implication of NO pathway activity in RES treatment, either NO precursor (L-arginine; L-A) or NO synthase inhibitor (L-NAME; L-N) was co-pretreated with EGCG; NO precursor treatment eliminated the protective effect of EGCG, in contrast to that NO synthase inhibitor treatment significantly increased the EGCG effects on cognitive and biochemical protection in RES-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the RES-induced impairment, as well as in the protective effect of EGCG in treating RES-induced impairment of memory. The above evidence provides a clinically relevant value for EGCG in preventing RES-induced cognitive dysfunction.
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Catequina/análogos & derivados , Trastornos de la Memoria/tratamiento farmacológico , Óxido Nítrico/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Arginina/farmacología , Catequina/farmacología , Catequina/uso terapéutico , Discriminación en Psicología/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Conducta Exploratoria/efectos de los fármacos , Glutatión/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Trastornos de la Memoria/inducido químicamente , NG-Nitroarginina Metil Éster/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Wistar , Reserpina/toxicidad , Olfato/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Intradialytic hypotension (IDH) carries adverse impact. Heart rate variability (HRV) represents autonomic cardiac regulation which influences intradialytic blood pressure. We aimed to evaluate the association between IDH and HRV. METHODS: This prospective study was carried out in a teaching hospital in Taiwan from June to August 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled and received HRV measurements for 4 times (before and during an index hemodialysis session). Patients were categorized by the changes of systolic blood pressure during the index hemodialysis into Group 1 (elevation >20 mmHg), Group 2 (decrease >20 mmHg), and Group 3 (others). Then we compared HRV indices among the three groups, and determined the indicators for IDH. RESULTS: One hundred and seventy-one patients (96 women, mean age 64.9 years) were enrolled and categorized into Group 1 (n = 47, 27.5 %), Group 2 (n = 45, 26.3 %) and Group 3 (n = 79, 46.2 %). Comparing with Group 1 and/or Group 3, Group 2 had significantly higher blood pressure at hemodialysis initiation (most p < 0.001) and statistically lower levels of HRV indices including variance, total power, very low-frequency, low-frequency and high-frequency since the middle phase of the hemodialysis. By logistic regression method, higher systemic blood pressure [odds ratio (OR) 1.048; p < 0.001], heart rate (OR 1.093; p = 0.021), low-frequency/high-frequency ratio (OR 1.715; p = 0.022), as well as lower variance (OR 0.639; p = 0.048) at hemodialysis initiation were independently associated with intradialytic blood pressure changes. CONCLUSIONS: HRV is a useful indicator for IDH among hemodialysis patients.
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Frecuencia Cardíaca , Hipotensión/fisiopatología , Fallo Renal Crónico/fisiopatología , Diálisis Renal/efectos adversos , Anciano , Femenino , Humanos , Hipotensión/etiología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Past studies in humans have demonstrated horizontal and vertical bone loss after six months following tooth extraction. Many biomaterials have been developed to preserve bone volume after tooth extraction. Type I collagen serves as an excellent delivery system for growth factors and promotes angiogenesis. Calcium phosphate ceramics have also been investigated because their mineral chemistry resembles human bone. The aim of this study was to compare the performance of a novel bioresorbable purified fibrillar collagen and hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) ceramic composite versus collagen alone and a bovine xenograft-collagen composite in beagles. Collagen plugs, bovine graft-collagen composite and HA/ß-TCP-collagen composite were implanted into the left and right first, second and third mandibular premolars, and the fourth molar was left empty for natural healing. In total, 20 male beagle dogs were used, and quantitative and histological analyses of the extraction ridge was done. The smallest width reduction was 19.09% ± 8.81% with the HA/ß-TCP-collagen composite at Week 8, accompanied by new bone formation at Weeks 4 and 8. The HA/ß-TCP-collagen composite performed well, as a new osteoconductive and biomimetic composite biomaterial, for socket bone preservation after tooth extraction.
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An antidepressant carrier was designed to maintain over 2 weeks of constant medication release. The carrier was injected into muscle, where cellular activity was employed to achieve the goal of constant release. Mesoporous hydroxyapatite (mesoHAP) was synthesized into an adequate size by a coprecipitation method; it then went through a series of hydrophobic surface modifications for olanzapine (OLZ) loading by physical absorption to produce mesoHAP-OLZ. Because of its hydrophobic nature, OLZ was not effectively released from mesoHAP-OLZ in an aqueous environment. However, once engulfed by macrophages, the lysosome/endosome hybrid ruptured due to alterations in osmotic pressure, resulting in the release of OLZ into the cytoplasm. OLZ was then exocytosed to the extracellular space due to a high calcium ion (Ca(2+)) concentration and finally reached the blood circulation. Our findings provide a useful treatment strategy to achieve long-term drug release with a single intramuscular (IM) injection, helping to solve the problem of nonadherent medication intake that often occurs in antidepressant therapy.
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Antidepresivos/administración & dosificación , Antidepresivos/farmacocinética , Benzodiazepinas/administración & dosificación , Benzodiazepinas/farmacocinética , Portadores de Fármacos/química , Durapatita/química , Células 3T3 , Animales , Humanos , Macrófagos/metabolismo , Ratones , Olanzapina , Porosidad , Ratas WistarRESUMEN
Reserpine has been confirmed to induce cognitive dysfunction and increase brain neural oxidative stress. Green tea catechins, particularly (-)epigallocatechin-3-gallate (EGCG), have strong antioxidative properties and can protect against numerous oxidative damages. In this study, we examined the possible protective effects of EGCG on reserpine-induced impairment of short-term memory in rats. Reserpine (1 mg/kg, intraperitoneal)-induced memory impairment was assessed using the social recognition task method; locomotor activity and the olfactory discrimination ability were not altered as measured by an open-field test and an olfactory discrimination test, respectively. EGCG treatment (100 and 300 mg/kg, intraperitoneal, for 7 days, starting 6 days before the reserpine injection) could improve the worsened social memory of reserpine-treated rats. Also, EGCG treatment reduced reserpine-induced lipid peroxidation and enhanced the antioxidation power in the hippocampi of reserpine-treated rats. These results suggest a protective effect of EGCG in treating reserpine-induced impairment of memory, most probably through its powerful antioxidative activities. Accordingly, EGCG may hold a clinically relevant value in preventing reserpine-induced cognitive dysfunction.
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Catequina/análogos & derivados , Memoria a Corto Plazo/efectos de los fármacos , Reserpina/antagonistas & inhibidores , Animales , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Catequina/farmacología , Interacciones Farmacológicas , Hipocampo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Conducta Social , Trastorno de la Conducta Social/inducido químicamente , Trastorno de la Conducta Social/prevención & controlRESUMEN
Stress induces reactive oxygen species (ROS) and causes alterations in brain cytoarchitecture and cognition. Green tea has potent antioxidative properties especially the tea catechin (-) epigallocatechin-3-gallate (EGCG). These powerful antioxidative properties are able to protect against various oxidative damages. In this study we investigated the impact of stress on rats' locomotor activity, learning and memory. Many tea catechins, including EGCG, were examined for their possible therapeutic effects in treating stress-induced impairment. Our results indicated that locomotor activity was decreased, and the learning and memory were impaired in stressed rats (SRs). EGCG treatment was able to prevent the decreased locomotor activity as well as improve the learning and memory in SRs. EGCG treatment was also able to reduce the increased oxidative status in SRs' hippocampi. The above results suggest a therapeutic effect of EGCG in treating stress-induced impairment of learning and memory, most likely by means of its powerful antioxidative properties.
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Antioxidantes/farmacología , Catequina/análogos & derivados , Discapacidades para el Aprendizaje/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Estrés Psicológico/psicología , Animales , Antioxidantes/uso terapéutico , Catequina/farmacología , Catequina/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Discapacidades para el Aprendizaje/etiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/etiología , Actividad Motora/efectos de los fármacos , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Restricción Física , Aprendizaje Espacial/efectos de los fármacos , Estrés Psicológico/complicaciones , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Reserpine-induced orofacial dyskinesia (OD) has been used for decades as an animal model for human tardive dyskinesia (TD) because both of them have pathophysiology strongly associated with striatal oxidative stress. Green tea catechins, especially (-) epigallocatechin-3-gallate (EGCG), have potent antioxidative effects and are able to protect against various oxidative injuries. In this study, we examined the potential protective effects of EGCG on reserpine-induced behavioral and neurochemical dysfunction in rats. Reserpine treatment (1mg/kgs.c. one injection every other day, three injections total) induced significant increases (p<0.001) in the frequency of vacuous chewing movement (VCM) and tongue protrusion (TP) as well as the duration of facial twitching (FT). EGCG treatment (100mg/kgi.p. for 11days, starting 7days before the reserpine injections) was able to prevent most of the reserpine-induced OD. Also, EGCG treatment was able to reduce the reserpine-induced lipid peroxidation (LPO) production, and enhances the antioxidation power in the striatum of reserpine-treated rats. The above results indicate that EGCG has a protective role against reserpine-induced OD, probably via its powerful antioxidative properties. Thus, EGCG may possible have a clinically relevant therapeutic effect in preventing, delaying or even treating TD.
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Catequina/análogos & derivados , Cuerpo Estriado/efectos de los fármacos , Trastornos del Movimiento/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Reserpina/farmacología , Animales , Catalasa/metabolismo , Catequina/uso terapéutico , Cuerpo Estriado/química , Modelos Animales de Enfermedad , Glutatión/análisis , Peroxidación de Lípido/efectos de los fármacos , Masculino , Trastornos del Movimiento/etiología , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
We aimed to develop a diabetes mellitus (DM) treatment that could be administered by intramuscular (IM) injection and it lasted for more than 3 days. The objective was to load insulin into the lattice space of hydroxyapatite (HAP) to prevent its release based on a concentration gradient or detachment from the surface, with insulin release being aided by cellular activity. To avoid insulin denaturation during the synthesis of insulin-loaded HAP (insHAP), we developed a single-step insHAP synthesis method by the hydrolysis of brushite. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) results suggested that insulin could be loaded into the HAP crystal lattice. After IM administration in rats with DM, the synthesized insHAP is thought to be engulfed by macrophages, escape from lysosome/endosome hybrids following disruption by osmotic pressure, and pumped into the extracellular space before entering the blood stream by diffusion. In rats with DM, the normal blood glucose level was maintained for 4 days after a single IM injection of the synthesized insHAP particles. Thus, insHAP may provide a breakthrough in insulin delivery for DM treatment, and may also be used to deliver fluorescent proteins, antibodies, and anticancer drugs.
RESUMEN
Oxidative stress induced by hypertension has been reported to cause alterations in neural cytoarchitecture and cognitive dysfunction. Green tea catechins, especially (-)-epigallocatechin-3-gallate (EGCG), have potent antioxidative properties and protect against various oxidative damages. In this study, we examined the impact of hypertension in rats on locomotor activity, learning, and memory, and EGCG was tested for its potential therapeutic effects in treating hypertension-induced impairment. Blood pressure was measured by the tail-cuff method to confirm high blood pressure in spontaneous hypertension rats (SHRs). Locomotor activity in the open field was increased in SHRs, along with learning and memory impairment in the Morris water maze. Daily EGCG treatment reduced the progressive increase in blood pressure in SHRs, and prevented most of the increased locomotor activity in addition to improving learning and memory. EGCG treatment also decreased the increased level of lipid peroxide production in SHRs and enhanced the antioxidation power in plasma that was observed to be decreased in SHRs. EGCG also decreased the concentration of reactive oxygen species in the hippocampi of SHRs. These indicate a therapeutic effect of EGCG in treating hypertension-induced learning and memory impairment, most probably through its powerful antioxidative properties.
Asunto(s)
Antioxidantes/farmacología , Catequina/análogos & derivados , Hipertensión/complicaciones , Trastornos de la Memoria/tratamiento farmacológico , Animales , Presión Sanguínea/efectos de los fármacos , Catequina/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipertensión/fisiopatología , Discapacidades para el Aprendizaje/tratamiento farmacológico , Discapacidades para el Aprendizaje/etiología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/etiología , Actividad Motora/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Especies Reactivas de Oxígeno/metabolismo , Té/químicaRESUMEN
(-)Epigallocatechin-3-gallate (EGCG), a tea catechin, has been known to cause many biological actions, such as anxiolytic and hypotensive effects in behavioral studies. However, to date, few reports investigate its neuronal modulation. In this study, intracellular recording was used to test the neuronal modulation of different catechins on locus coeruleus (LC) neuron, which has been demonstrated to be affected by cardiovascular function regulation and stressful events. Several catechins (1 -- 1,000 microM) were tested, including: (-)catechin (C), (-)catechingallate (CG), (-)epicatechin (EC), (-)epicatechin-3-gallate (ECG), (?)epigallocatechin (EGC) and EGCG. The results showed that catechins EC, ECG, EGC and EGCG could inhibit the spontaneous firing of the LC neurons; furthermore, these catechins show potency and efficacy in the order of EGCG>ECG>EC approximately EGC. Among the tested catechins, EGCG was the most potent in inhibiting LC's spontaneous firing with IC(50) of 20.5 microM. This caused us to further examine the EGCG's desensitization and tolerance properties. When continuously administering EGCG at 1 -- 300 microM for 20 min, no acute desensitization appeared. However, repeated applications of 300 microM EGCG at 5 min each time showed different results. The second and third applications induced less responses compared to that of the first application, suggesting a development of tolerance towards EGCG in inhibiting LC neuronal activity. Our data suggest that EGCG can inhibit LC neuron's spontaneous firing in a dose-dependent manner, with developed tolerance only when high concentration of EGCG is repeatedly applied.