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1.
Preventive and therapeutic efficacies of resveratrol on several lower gastrointestinal (GI) diseases (e.g., colorectal cancer,
colitis) are well documented. To overcome the problems due to its rapid absorption and metabolism at the upper GI tract, a
delayed release formulation of resveratrol was designed to treat these lower GI diseases. The current study aimed to develop
a delayed release formulation of resveratrol as multiparticulate pectinate beads by varying different formulation parameters.
Zinc-pectinate (Zn-pectinate) beads exhibited better delayed drug release pattern than calcium-pectinate (Ca-pectinate) beads.
The effects of the formulation parameters were investigated on shape, size, Zn content, moisture content, drug encapsulation
efficiency, swelling–erosion, and resveratrol retention pattern of the formulated beads. Upon optimization of the formulation
parameters in relative to the drug release profiles, the optimized beads were further subjected to morphological, chemical
interaction, enzymatic degradation, and stability studies. Almost all prepared beads were spherical with ∼1 mm diameter and
efficiently encapsulated resveratrol. The formulation parameters revealed great influence on resveratrol retention and swelling–erosion
behavior. In most of the cases, the drug release data more appropriately fitted with zero-order equation. This study demonstrates
that the optimized Zn-pectinate beads can encapsulate very high amount of resveratrol and can be used as delayed release formulation
of resveratrol. 相似文献
2.
de Oliveira MR da Rocha RF Stertz L Fries GR de Oliveira DL Kapczinski F Moreira JC 《Neurochemical research》2011,36(3):506-517
Vitamin A supplementation has caused concern among public health researchers due to its ability in decreasing life quality
from acute toxicological effects to increasing mortality rates among vitamin supplement users. For example, it was described
cognitive decline (i.e. irritability, anxiety, and depression) in patients subjected to long-term vitamin A therapy, as occurs
in cancer treatment. However, the mechanism by which vitamin A affects mammalian cognition is not completely understood. Then,
we performed the present work to investigate the effects of vitamin A supplementation at clinical doses (1,000–9,000 IU/kg day−1) for 28 days on rat hippocampal nitrosative stress levels (both total and mitochondrial), bioenergetics states, brain-derived
neurotrophic factor (BDNF), alpha- and beta-synucleins, BiP and dopamine receptor 2 (D2 receptor) contents, and glutamate
uptake. We observed mitochondrial impairment regarding respiratory chain function: increased complex I-III, but decreased
complex IV enzyme activity. Also, decreased BDNF levels were observed in vitamin A-treated rats. The present data demonstrates,
at least in part, that mitochondrial dysfunction and decreased BDNF and D2 receptors levels, as well as decreased glutamate
uptake may take an important role in the mechanism behind the previously reported cognitive disturbances associated to vitamin
A supplementation. 相似文献
3.
Chien-Chih Chen Li-Wen Hsu Li-Tung Huang Tiao-Lai Huang 《Neurochemical research》2010,35(7):1098-1104
Neurotrophins, including the brain-derived neurotrophic factor (BDNF), are essential for regulating neuronal differentiation
in developing brains. BDNF and its receptor tyrosine kinase receptor B (TrkB) are involved in neuronal signaling, survival
and plasticity. Cyclosporine A (CsA) is a potent immunosuppressive agent which prevents allograft rejection in organ transplantation
and various immunological diseases. We investigated whether chronic administration of CsA decreases BDNF gene expression in
rats, and the influence of CsA on mRNA levels of TrkB receptors was also examined. For 30 days of CsA (10 mg/kg/day) administration,
the expression of BDNF and TrkB mRNA was significantly decreased in the hippocampus and midbrain, but there was no significant
difference in the cortex. CsA (0, 1, 5 10, 15 ug/ml) down-regulated BDNF and TrkB gene expression through cultured SH-SY5Y
cells, as did all-trans retinoic acid (ATRA), and there was no effect on cell viability. These experimental results indicate
that suppression of the BDNF and TrkB mRNA, protein level of BDNF expression in the hippocampus and midbrain may be related
to altered behavior observed following chronic administration of CsA. A common mechanism of adverse effects of CsA induced
depressive symptoms may involve neurotoxicity mediated by down-regulation of brain BDNF and TrkB. 相似文献
4.
Hyperactivation of the hypothalamic–pituitary–adrenal axis and the associated hippocampal atrophy were observed in patients
with depression, which could be ameliorated by the treatment with antidepressants. Therefore, neuroprotection has been proposed
to be one of the acting mechanisms of antidepressant. Our previous studies have showed that treating mice with piperine produced
antidepressant-like effect in animal models of behavioral despair. This study aimed to examine the protective effect of piperine
treatment on corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that piperine
co-treatment revealed a differential effect on the cytotoxicity of corticosterone and had its maximum inhibitory effect at
1 μM. Piperine (1 μM) co-treatment also significantly decreased intracellular reactive oxygen species level, and enhanced
superoxide dismutase activity and total glutathione level in corticosterone-treated PC12 cells. In addition, piperine (1 μM)
co-treatment was found to reverse the decreased brain-derived neurotrophic factor (BDNF) mRNA level caused by corticosterone
in PC12 cells. The results suggest that piperine exerts a neuroprotective effect on corticosterone-induced neurotoxicity in
PC12 cells, at least in part, via the inhibition of oxidative stress and the upregulation of BDNF mRNA expression. This neuroprotective
effect may be one of the acting mechanisms accounts for the in vivo antidepressant activity of piperine. 相似文献
5.
The use of comet assay in measuring DNA damage and repair efficiency in child,adult, and old age populations 总被引:1,自引:0,他引:1
Piperakis SM Kontogianni K Karanastasi G Iakovidou-Kritsi Z Piperakis MM 《Cell biology and toxicology》2009,25(1):65-71
In the present study, we used the Comet assay to estimate basal DNA damage in three distinct populations aged 5–10, 40–50,
and 60–70 years old. The DNA damage induced by hydrogen peroxide and γ-irradiation in the lymphocytes of these populations,
as well as their repair activity, was also studied. Finally, we measured apoptosis and necrosis after the effect of these
agents. Our results indicate that the older population (60–70 years old) showed higher basal levels of DNA damage and was
more sensitive to the effects of the DNA-damaging agents than the adult one (40–50 years old), who, in turn, was more sensitive
than the younger population (5–10 years old). A decline of the repair efficiency with age to the DNA damage induced by the
two agents was also observed. Apoptosis and necrosis were also affected by age. 相似文献
6.
This preliminary study was planned to investigate the effects of resveratrol on oxidative–nitrosative stress markers and on
trace element concentrations in blood and on circulatory system parameters in rats. Twenty-five Sprague–Dawley male rats,
10–12 weeks old, with mean body weight of 295 g were used in the study. Administration of resveratrol (0.5 ml/day) was performed
in experimental group in 10 days. In control (n = 10) and in experimental groups (n = 15), after 1 week training period, systolic arterial blood pressures and heart rates were recorded daily. At the end of
the tenth day, blood samples of control and experimental groups were drawn. Total nitrite, nitrite, nitrate, malondialdehyde,
copper, zinc concentrations in plasma, superoxide dismutase, and catalase activities and copper, zinc concentrations in red
cell were determined both in control and experimental groups. Alterations in oxidative and nitrosative stress markers, trace
element concentrations, and circulatory system parameters in experimental group compared to controls were observed. The results
of this study were discussed according to the effect of resveratrol.
This study was presented at “The 5th International Congress of Pathophysiology (ISP2006)” June 28–July 1, 2006 Beijing, China. 相似文献
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10.
D. Jantas M. Szymanska B. Budziszewska W. Lason 《Apoptosis : an international journal on programmed cell death》2009,14(7):900-912
Memantine, a clinically used NMDA receptor antagonist possesses neuroprotective properties, but the exact mechanisms of its
beneficial action on neuronal survival are poorly recognized. In the present study, some intracellular mechanisms of memantine
effects on staurosporine-evoked cell death were investigated in primary cortical neurons. Memantine (0.1–2 μM) suppressed
neuronal apoptosis evoked by staurosporine in 7 DIV cortical neurons, whereas other antagonists of NMDA receptor, MK-801 (1 μM)
and AP-5 (100 μM) were ineffective. The anti-apoptotic effects of memantine were not connected with any changes in cytoplasmic
calcium concentration or reactive oxygen species level. The immunoblot analysis showed that the staurosporine induced a decrease
in p-Akt protein kinase level and that this effect was reversed by memantine treatment. Moreover, the PI3-K inhibitors, wortmannin
and LY 294002 attenuated the anti-apoptotic action of memantine on staurosporine-induced cell damage. Furthermore, the ELISA
studies showed increased cellular and released BDNF protein level after combined treatment with memantine and staurosporine.
There was no effect of memantine on the activation and expression of other protein kinases involved in the mechanism of cellular
survival, i.e. ERK1/2, JNK and GSK3-β. The obtained data suggest an NMDAR-independent action of memantine in attenuation of
neuronal apoptosis and point to the engagement of BDNF and PI3-K/Akt pathway in these processes. 相似文献
11.
A full-length metallothionein-1(MT-1) cDNA was cloned from the Chinese mitten crab, Eriocheir sinensis, based upon the hepatopancreas cDNA library. The full-length cDNA contained a single 180 bp open reading frame that encoded
a 59 amino acid protein. The deduced amino acid sequence was cysteine (Cys)-rich, with residues observed in patterns characteristic
of other reported MTs: Cys–X–Cys, Cys–X–X–Cys, or Cys–X–X–X–Cys. Gene structure obtained via PCR yielded a 3816 bp gene, which
was comprised of three exons and two introns arranged in a “3 + 2” pattern. The cloned 5′flanking region (1,735 bp) contained
several predicted binding sites, which included MREs, AP-1, SP1, USF, GATA, HNF-1, and HSF. MT-1 mRNA expression analysis
revealed that while levels were highest in the hepatopancreas, expression was abundant in testis and thoracic ganglia, moderate
in intestine (P < 0.05), and weak in other tissues (P < 0.05). MT-1 mRNA expression exhibited reproductive variation in the male, with levels approximately tenfold greater in
August, during seasonal gonadal maturation, compared to other times of the year. Cu2+ exposure via tank water (0–1 mg/l for 7 days) resulted in a dose-dependent bell curve response in MT-1 mRNA expression, with
peak expression observed after exposure to 0.1 mg/l Cu2+. A time course experiment (0.1 mg/l Cu2+ over 9 days) revealed MT-1 mRNA expression peaked sharply on day 5 before gradually decreasing with prolonged exposure. In
the present report, we provide sequence analysis of the first MT-1 gene cloned in E. sinensis, and evidence that its physiological and toxicological regulation is evolutionary conserved. 相似文献
12.
Lisete Haas Luis V. C. Portela Ana Elisa Böhmer Jean Pierre Oses Diogo R. Lara 《Neurochemical research》2010,35(5):830-834
Brain-derived neurotrophic factor (BDNF) is involved in neuronal survival and synaptic plasticity of the central and peripheral
nervous system. BDNF appears to modulate nociceptive sensory inputs and pain hypersensitivity and has been studied in pathological
situations, including chronic pain conditions and major depression. Increased serum BDNF levels have been recently reported
in fibromyalgia (FM). In the present study, we assessed plasma BDNF levels in patients with FM and controls. Plasma BDNF was
measured from 30 female patients with FM and 30 healthy age- and gender-matched volunteers using an enzyme immunoassay. FM
patients showed higher levels of BDNF (FM = 167.1 ± 171.2 pg/mL) when compared with the control group (control = 113.8 ± 149.6 pg/mL)
(P = 0.049; Mann–Whitney test). Six out of 30 controls presented superior values to the medium (15/15) of the patients with
fibromyalgia (129 pg/mL) (P = 0.029, Fisher exact test). There was no correlation between plasma BDNF levels and age, disease duration, pain score, number
of pain points and HAM-D score. Our results confirm previous findings of increased plasma BDNF levels in patients with FM,
suggesting that BDNF may be involved in the pathophysiology of Fibromyalgia, despite high levels of depression. 相似文献
13.
Van B. Lu S. Balasubramanyan J. E. Biggs M. J. Stebbing S. L. Gustafson K. Todd A. Lai D. Dawbarn W. F. Colmers K. Ballanyi P. A. Smith 《Neurophysiology》2007,39(4-5):272-283
Chronic constriction injury (CCI) of the rat sciatic nerve increases the dorsal horn excitability. This “central sensitization”
leads to behavioral manifestations analogous to those related to human neuropathic pain. We found, using whole-cell recording
from acutely isolated spinal cord slices, that 7-to 10-day-long CCI increases excitatory synaptic drive to putative excitatory
“delay”-firing neurons in the substantia gelatinosa but attenuates that to putative inhibitory “tonic”-firing neurons. A defined-medium organotypic culture (DMOTC) system was
used to investigate the long-term actions of brain-derived neurotrophic factor (BDNF) as a possible instigator of these changes.
When all five neuronal types found in the substantia gelatinosa were considered, BDNF and CCI produced similar patterns, or “footprints,” of changes across the whole population. This pattern
was not seen with another putative “pain mediator,” interleukin 1β. Thus, BDNF decreased synaptic drive to “tonic” neurons
and increased synaptic drive to “delay” neurons. Actions of BDNF on “delay” neurons were presynaptic and involved increased
mEPSC frequency and amplitude without changes in the function of postsynaptic AMPA receptors. By contrast, BDNF exerted both
pre-and post-synaptic actions on “ tonic” cells to reduce the mEPSC frequency and amplitude. These differential actions of
BDNF on excitatory and inhibitory neurons contributed to a global increase in the dorsal horn network excitability as assessed
by the amplitude of depolarization-induced increases in the intracellular [Ca2+]. Experiments with the BDNF-binding protein TrkB-d5 provided additional evidence for BDNF as a harbinger of neuropathic pain.
Thus, the cellular processes altered by BDNF likely contribute to “central sensitization” and hence to the onset of neuropathic
pain.
Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 315–326, July–October, 2007. 相似文献
14.
The effect of dietary selenium supplementation on cadmium absorption and retention in suckling rats 总被引:1,自引:0,他引:1
Selenium (Se) reduces cadmium (Cd) toxicity in adult animals, but its effects in newborn animals are still unknown. This study
investigated Cd (as CdCl2) absorption, distribution, and retention in suckling rats receiving oral Se supplementation (as Na2SeO3) in equimolar doses (8 μmol Cd and/or Se per kg b.w./day). Selenium was given either before and during Cd exposure (Sepre + Cd group; pre-treatment group) or only during Cd exposure (Se + Cd group). Rats were treated from postnatal day (PND) 6–14
as follows: controls (H2O, PND 6–14), Se (PND 10–14), Cd (PND 10–14), Sepre + Cd (Se PND 6–14 + Cd PND 10–14) and Se + Cd (Se + Cd PND 10–14). Selenium supplementation, especially pre-treatment, decreased
Cd levels in the blood, brain, liver and kidney of suckling rats. Selenium levels in plasma, brain, and kidney also decreased.
These findings suggest that higher Se intake could efficiently reduce Cd retention during the suckling period. 相似文献
15.
CSD mRNA expression in rat testis and the effect of taurine on testosterone secretion 总被引:1,自引:0,他引:1
Jiancheng Yang Gaofeng Wu Ying Feng Changmian Sun Shumei Lin Jianmin Hu 《Amino acids》2010,39(1):155-160
In the present study, the cysteine sulfinate decarboxylase (CSD) mRNA expression was detected in rat testis by RT-PCR. The
results showed that CSD mRNA was expressed in rat testis, and the putative encoded-amino acid sequence was exactly the same
as that in rat liver which was already known. At the same time, the effects of taurine on testosterone secretion were investigated
both in vivo and in vitro. In vivo, taurine were administered to male rats by tap water. The results showed that taurine obviously
stimulated the secretion of FSH, LH and testosterone in serum, but showed no significant effect on the secretion of estradiol.
Taurine administered in water could significantly increase the concentration of taurine in the blood and testis of rats. In
vitro, cultured Leydig cells were treated with taurine independently or incubated with human chorionic gonadotropin (HCG)
and progesterone. The results showed that taurine had biphasic effects on basal testosterone secretion in cultured Leydig
cells. Low concentrations of taurine (0.1–100 μg/ml) could stimulate testosterone secretion, whereas high concentration of
taurine (400 μg/ml) could inhibit testosterone secretion. Testosterone secretion stimulated by HCG was significantly increased
by 10 and 100 μg/ml of taurine administration, and obviously decreased by treating with 400 μg/ml of taurine. Testosterone
secretion induced by progesterone was significantly stimulated by treating with 1.0 and 10 μg/ml of taurine, however, it was
significantly inhibited when treated with 400 μg/ml of taurine. Meanwhile, the effect of silencing CSD mRNA by siRNA on testosterone
secretion was analyzed. The results showed that testosterone secretion was obviously decreased after the inhibition of CSD
mRNA expression in cultured Leydig cells. These results indicated that taurine can be synthesized in rat testis by CSD pathway,
and it plays important roles in testosterone secretion both in vivo and in vitro which need to be further investigated. 相似文献
16.
Jun Yang Xiao-Dong Zhang Jian Yang Jia-Wang Ding Zhao-Qi Liu Shu-Guo Li Rui Yang 《Molecular biology reports》2011,38(5):3037-3044
To determine whether the cardioprotection effect of fluvastatin mediates by toll-like receptor 4 (TLR4) signaling pathway,
fifty Sprague–Dawley rats were randomly divided into five groups: sham operation group, ischemia/reperfusion (I/R) group,
fluvastatin groups (high-dosage, medium-dosage, low-dosage, n = 10 in each group). Except sham operation group, the rest four groups of rats were artificially afflicted with coronary
occlusion for 30 min, then reperfusion 2 h. Light microscope and transmission electronic microscope were used to observe structural
changes of myocardium. RT–PCR was used to measure TLR4 mRNA expression level, TLR4 protein expression was detected by immunohistochemistry.
Western blot was used to measure myocardial NF-κB protein level; ELISA was used to measure the level of TNF-α in myocardium.
The results demonstrated that fluvastatin treatment markedly decreased ischemic injury caused by ischemia/reperfusion, and
inhibited the expression levels of TLR4, TNF-α and NF-κB, all of which up-regulated by ischemia/reperfusion. Taken together,
our results suggest that proper dosage of fluvastatin may have protective effect on the ischemic injury mediated by ischemia/reperfusion
in the hearts, which might be associated with inhibition of TLR4 signaling pathway and inflammatory response during ischemia/reperfusion. 相似文献
17.
Shyam Sunder Gajula Vijay Kumar Chelasani Arun K. Panda V. L. N. Raju Mantena Rama Rao Savaram 《Biological trace element research》2011,139(2):177-187
The purpose of this study was to investigate the interaction and main effects of supplemental Zn and Mn levels on growth,
tissue mineral uptake, and immune response in broiler chicken. A basal diet of corn–soybean meal was supplemented with Zn
at 40, 80, or 160 ppm and Mn at 60, 120, or 240 ppm in a factorial pattern to constitute nine experimental diets. Each diet
was offered to nine replicates of six chicks in stainless steel battery brooders. At 35 days of age, body weight gain, feed
conversion efficiency, hock joint scores, tibia weight, tibia strength, and percent ash were not influenced by Zn and Mn levels
and their interactions. The concentration of Zn (207–238 ppm) and Mn (11.8–16.3 ppm) in tibia increased linearly with progressive
raise of mineral inclusion in diets. Mn at 240 ppm level caused higher retention of Zn in tibia, but not vice versa. Manganese
either alone or in combination with Zn (Zn160/Mn120 ppm) significantly reduced Cu retention (10.1–7.2 ppm) in tibia. Even
in the hepatic tissue, Zn (93.6–98.4 ppm) and Mn (9.3–10.2 ppm) concentration increased linearly with their levels of inclusion
in diets. When Zn and Mn levels were maintained at 4:3 ratio (80:60 or 160:120 ppm), the concentration of Zn (100–106 ppm)
in liver was higher, while that of Mn was significantly more with low level of Zn (40 ppm) in diet. However, Mn supplementation
at 120 ppm level and above significantly decreased Cu accumulation (19.5–17.1 ppm) in liver, but Mn × Zn interaction had no
effect on Cu retention. The immune response measured as antibody titers to sheep RBC increased (5.9–7.9 log2) significantly with higher Zn (80 ppm) supplementation and cell-mediated immune response to phytohemagglutinin (0.57–0.78)
with Mn level at 120 ppm. In summary, Zn (40 ppm) and Mn (60 ppm) as recommended by NRC was sufficient for broiler performance
and bone parameters. Mn complimented Zn retention in tibia and antagonized Cu in tibia and liver tissues. Higher levels of
Zn (80 ppm) and Mn (120 ppm) than those recommended by NRC were needed for improved immune response in broilers at 35 days
of age. 相似文献
18.
19.
Resveratrol Increases Glutamate Uptake, Glutathione Content, and S100B Secretion in Cortical Astrocyte Cultures 总被引:3,自引:0,他引:3
de Almeida LM Piñeiro CC Leite MC Brolese G Tramontina F Feoli AM Gottfried C Gonçalves CA 《Cellular and molecular neurobiology》2007,27(5):661-668
Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenol present in grapes and red wine, which has antioxidant properties and a wide range of other biological
effects. In this study, we investigated the effect of resveratrol, in a concentration range of 10–250 μM, on primary cortical
astrocytes; evaluating cell morphology, parameters of glutamate metabolism such as glutamate uptake, glutamine synthetase
activity and glutathione total content, and S100B secretion. Astrocyte cultures were prepared of cerebral cortex from neonate
Wistar rats. Morphology was evaluated by phase-contrast microscopy and immunocytochemistry for glial fibrillary acidic protein
(GFAP). Glutamate uptake was measured using l-[2,3-3H]glutamate. Glutamine synthetase and content of glutathione were measured by enzymatic colorimetric assays. S100B content
was determined by ELISA. Typical polygonal morphology becomes stellated when astrocyte cultures were exposed to 250 μM resveratrol
for 24 h. At concentration of 25 μM, resveratrol was able to increase glutamate uptake and glutathione content. Conversely,
at 250 μM, resveratrol decreased glutamate uptake. Unexpectedly, resveratrol at this high concentration increased glutamine
synthetase activity. Extracellular S100B increased from 50 μM upwards. Our findings reinforce the protective role of this
compound in some brain disorders, particularly those involving glutamate toxicity. However, the underlying mechanisms of these
changes are not clear at the moment and it is necessary caution with its administration because elevated levels of this compound
could contribute to aggravate these conditions. 相似文献
20.
Proliferation and cellular aggregation are both crucial features for survival and self-renewal of primordial germ cells (PGCs).
Adhesive proteins play pivotal roles in cell–cell adhesion and signal exchanges under the influence of cytokines, growth factors
and bioactive metabolites such as retinoic acid (RA). In this study, proliferation-promoting effect of RA on chicken PGCs
was investigated by revealing changes in adhesive proteins E-cadherin and α/β catenins. PGCs were isolated from the genital
ridge of 4-day-old chicken embryos and cultured on embryonic fibroblast feeder. RA (10−7–10−5 M) increased PGCs aggregation and mRNA expression of E-cadherin and α/β-catenins. Furthermore, E-cadherin and β-catenin protein
expression levels were increased by RA treatment. However, RA-elicited effect was significantly attenuated by a PKC inhibitor
H7. In addition, the number and area of PGC colonies were increased by RA treatment at 10−7–10−5 M. Again, this increase was reduced by combined treatment of H7. The proliferating effect of RA on PGCs was further confirmed by increased mRNA expression of cyclins, CCND1 and CCNE1, and cyclin-dependent kinases 6 and 2, which are critical for G1–S progression in cell cycle. Moreover, flow cytometry analysis
confirmed that RA-treated PGC populations displayed a significant increase in the proportion of S and G2 phase cells. Likewise,
this stimulating action was hindered by combined H7 treatment. These results indicate that RA, as a bioactive metabolite of vitamin A, may promote PGC proliferation and increase
intercellular aggregation of PGCs via E-cadherin and α/β-catenins expression through the PKC signaling pathway. 相似文献