共查询到20条相似文献,搜索用时 390 毫秒
1.
Ana Figueiras Jorge M. G. Sarraguça Alberto A. C. C. Pais Rui A. Carvalho J. Francisco Veiga 《AAPS PharmSciTech》2010,11(1):233-240
In this study, we investigate how the effect of l-arginine (ARG) and cyclodextrins upon omeprazole (OME) stability and solubility. The effect of the presence of ARG on the
apparent stability constants (K1:1) of the inclusion complexes formed between OME and each cyclodextrin, β-cyclodextrin (βCD), and methyl-β-cyclodextrin (MβCD)
is studied by phase solubility diagrams and nuclear magnetic resonance (NMR) spectroscopy. The interaction of OME with those
cyclodextrins, in the presence of ARG, is characterized using NMR spectroscopy and molecular dynamics simulations. ARG significantly
increases the drug solubility and complex stability, in comparison to inclusion complexes formed in its absence. The effect
is more pronounced for the OME:βCD complex. ARG also contributes to a larger stability of OME when free in aqueous solution.
The combination of ARG with cyclodextrins can represent an important tool to develop stable drug formulations. 相似文献
2.
The purpose of this research work was to establish mucoadhesive buccal devices of propranolol hydrochloride (PRH) in the forms
of bilayered and multilayered tablets. The tablets were prepared using sodium carboxymethylcellulose (SCMC) and Carbopol-934
(CP) as bioadhesive polymers to impart mucoadhesion and ethyl cellulose (EC) to act as an impermeable backing layer. Buccal
devices were evaluated by different parameters such as weight uniformity, content uniformity, thickness, hardness, surface
pH, swelling index, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, and in vitro drug permeation.
As compared with bilayered tablets, multilayered tablets showed slow release rate of drug with improved ex vivo bioadhesive
strength and enhanced ex vivo mucoadhesion time. The mechanism of drug release was found to be non-Fickian diffusion (value
of n between 0.5 and 1.0) for both the buccal devices. The stability of drug in both the optimized buccal devices was tested
for 6 hours in natural human saliva; both the buccal devices were found to be stable in natural human saliva. The present
study concludes that mucoadhesive buccal devices of PRH can be a good way to bypass the extensive hepatic first-pass metabolism
and to improve the bioavailability of PRH.
Published: March 16, 2007 相似文献
3.
Nicotine (NCT) buccal tablets consisting of sodium alginate (SA) and nicotine–magnesium aluminum silicate (NCT–MAS) complexes
acting as drug carriers were prepared using the direct compression method. The effects of the preparation pH levels of the
NCT–MAS complexes and the complex/SA ratios on NCT release, permeation across mucosa, and mucoadhesive properties of the tablets
were investigated. The NCT–MAS complex-loaded SA tablets had good physical properties and zero-order release kinetics of NCT,
which indicate a swelling/erosion-controlled release mechanism. Measurement of unidirectional NCT release and permeation across
porcine esophageal mucosa using a modified USP dissolution apparatus 2 showed that NCT delivery was controlled by the swollen
gel matrix of the tablets. This matrix, which controlled drug diffusion, resulted from the molecular interactions of SA and
MAS. Tablets containing the NCT–MAS complexes prepared at pH 9 showed remarkably higher NCT permeation rates than those containing
the complexes prepared at acidic and neutral pH levels. Larger amounts of SA in the tablets decreased NCT release and permeation
rates. Additionally, the presence of SA could enhance the mucoadhesive properties of the tablets. These findings suggest that
SA plays the important role not only in controlling release and permeation of NCT but also for enhancing the mucoadhesive
properties of the NCT–MAS complex-loaded SA tablets, and these tablets demonstrate a promising buccal delivery system for
NCT. 相似文献
4.
The aim of the present study was to develop and evaluate a buccal adhesive tablet containing ondansetron hydrochloride (OH).
Special punches and dies were fabricated and used while preparing buccal adhesive tablets. The tablets were prepared using
carbopol (CP 934), sodium alginate, sodium carboxymethylcellulose low viscosity (SCMC LV), and hydroxypropylmethylcellulose
(HPMC 15cps) as mucoadhsive polymers to impart mucoadhesion and ethyl cellulose to act as an impermeable backing layer. The
formulations were prepared by direct compression and characterized by different parameters such as weight uniformity, content
uniformity, thickness, hardness, swelling index, in vitro drug release studies, mucoadhesive strength, and ex vivo permeation study. As compared with the optimized formulation composed of OH—5 mg, CP 934—30 mg, SCMC LV—165 mg, PEG 6000—40 mg,
lactose—5 mg, magnesium stearate—1.5 mg, and aspartame—2 mg, which gave the maximum release (88.15%), non-bitter (OH) that
form namely ondansetron base and complexed ondansetron was used in order to make the selected formulation acceptable to human.
The result of the in vitro release studies and permeation studies through bovine buccal mucosa revealed that complexed ondansetron gave the maximum
release and permeation. The stability of drug in the optimized adhesive tablet was tested for 6 h in natural human saliva;
both the drug and device were found to be stable in natural human saliva. Thus, buccal adhesive tablet of ondansetron could
be an alternative route to bypass the hepatic first-pass metabolism and to improve the bioavailability of (OH). 相似文献
5.
Gazzi Shanker Chegonda K. Kumar Chandra Sekhara Rao Gonugunta B. Vijaya Kumar Prabhakar Reddy Veerareddy 《AAPS PharmSciTech》2009,10(2):530-539
The study aim was concerned with formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride
tablets, which is extensively metabolized by liver. The tablets were prepared by direct compression using bioadhesive polymers
such as hydroxylpropyl methylcellulose K4M, sodium carboxymethyl cellulose alone, and a combination of these two polymers.
In order to improve the permeation of drug, different permeation enhancers like beta-cyclodextrin (β-CD), hydroxylpropyl beta-cyclodextrin
(HP-β-CD), and sodium deoxycholate (SDC) were added to the formulations. The β-CD and HP-β-CD were taken in 1:1 molar ratio
to drug in formulations. Bioadhesion strength, ex vivo residence time, swelling, and in vitro dissolution studies and ex vivo permeation studies were performed. In vitro release of optimized bioadhesive buccal tablet was found to be non-Fickian. SDC was taken in 1%, 2%, and 3% w/w of the total tablet weight. Stability studies in natural saliva indicated that optimized formulation has good stability in
human saliva. In vivo mucoadhesive behavior of optimized formulation was performed in five healthy male human volunteers and subjective parameters
were evaluated. 相似文献
6.
The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive
polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer.
The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling
index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets
containing Na-alginate and CP in the ratio of 5∶1 (F2) had the maximum percentage of in vitro drug release without disinte-gration
in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface
pH of all tablets was found to be satis-factory (7.0±1.5), close to neutral pH; hence, buccal cavity irritation should not
occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics.
The formulation F4 was optimized based on good biodhesive strength (28.9±0.99 g) and sustained in vitro drug permeation (68.65%±3.69%
for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found
to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced
tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration.
Published: September 21, 2007 相似文献
7.
Tatiana Borisova Roman Sivko Arseniy Borysov Natalia Krisanova 《Cellular and molecular neurobiology》2010,30(7):1013-1023
The effect of the cholesterol-depleting agent methyl-β-cyclodextrin (MβCD) on exocytotic, transporter-mediated, tonic release,
the ambient level and uptake of l-[14C]glutamate was assessed in rat brain synaptosomes using different methodological approaches of MβCD application. The addition
of 15 mM MβCD to synaptosomes (the acute treatment, AT) immediately resulted in the extraction of cholesterol and in a two
times increase in the extracellular l-[14C]glutamate level. When 15 mM MβCD was applied to synaptosomes for 35 min followed by washing of the acceptor (the long-term
pretreatment, LP), this level was only one-third higher than in the control. The opposite effects of MβCD on tonic l-[14C]glutamate release and glutamate transporter reversal were found in AT and LP. Tonic release was dramatically enlarged in
AT, but decreased after LP. Transporter-mediated release was increased several times in AT, but attenuated in LP. Depolarization-evoked
exocytotic release of l-[14C]glutamate was completely lost in AT, whereas after LP, it was decreased by half in comparison with the control. Na+-dependent l-[14C]glutamate uptake was decreased by ~60% in AT, whereas in LP, it was lowered by ~40% only. The presence of MβCD in the incubation
media during AT caused dramatic dissipation of the proton gradient of synaptic vesicles that was shown with the pH-sensitive
dye acridine orange, whereas after LP, no statistically significant changes were registered in synaptic vesicle acidification.
It was concluded that the diverse changes in glutamate transport in AT and LP were associated with the difference in the functional
state of synaptic vesicles. 相似文献
8.
The purpose of this research was to develop and evaluate buccal mucoadhesive controlled release tablets of lercanidipine hydrochloride
using polyethylene oxide and different viscosity grades of hydroxypropyl methylcellulose individually and in combination.
Effect of polymer type, proportion and combination was studied on the drug release rate, release mechanism and mucoadhesive
strength of the prepared formulations. Buccal mucoadhesive tablets were made by direct compression and were characterized
for content uniformity, weight variation, friability, surface pH, thickness and mechanism of release. In order to estimate
the relative enhancement in bioavailability one optimized formulation was evaluated in rabbits. Further, placebo tablets were
also evaluated for acceptability in human subjects. Results indicated acceptable physical characteristics of designed tablets
with good content uniformity and minimum weight variation. Drug release and mucoadhesive strength were found to depend upon
polymer type, proportion and viscosity. The formulations prepared using poly ethylene oxide gave maximum mucoadhesion. The
release mechanism of most formulations was found to be of anomalous non-Fickian type. In vivo studies of selected formulation in rabbits demonstrated significant enhancement in bioavailability of lercanidipine hydrochloride
relative to orally administered drug. Moreover, in human acceptability studies of placebo formulations, the designed tablets
adhered well to the buccal mucosa for more than 4 h without causing any discomfort. It may be concluded that the designed
buccoadhesive controlled release tablets have the potential to overcome the disadvantage of poor and erratic oral bioavailability
associated with the presently marketed formulations of lercanidipine hydrochloride. 相似文献
9.
Mamdouh M. Ghorab Heba M. Abdel-Salam Marwa A. El-Sayad Mohammed M. Mekhel 《AAPS PharmSciTech》2004,5(4):63-68
The purpose of this research was to evaluate β-cyclodextrin (β-CD) as a vehicle, either singly or in blends with lactose (spray-dried
or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of β-CD was investigated. The
tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated
for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to
thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution
studies. The effect of β-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced
2-way crossover study. Phase-solubility studies indicated an AL-type diagram with inclusion complex of 1∶1 molar ratio. The powder blends and granules of all formulations showed satisfactory
flow properties, compressibility, and drug content. All tablet formations prepared by direct compression or wet granulation
showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of β-CD
in the formulations up to 30%. The mean pharmacokinetic parameters (Cmax, Ke, and area under the curve [AUC]0−∞) were significantly increased in presence of β-CD. These results suggest that β-CD would facilitate the preparation of meloxicam
tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between
tablets prepared by direct compression and those prepared by wet granulation. Also, β-CD is particularly useful for improving
the oral bioavailablity of meloxicam. 相似文献
10.
The present research work focused on the comparative assessment of porous versus nonporous films in order to develop a suitable buccoadhesive device for the delivery of glibenclamide. Both films were prepared by solvent casting technique using the 32 full factorial design, developing nine formulations (F1–F9). The films were evaluated for ex vivo mucoadhesive force, ex vivo mucoadhesion time, in vitro drug release (using a modified flow-through drug release apparatus), and ex vivo drug permeation. The mucoadhesive force, mucoadhesion time, swelling index, and tensile strength were observed to be directly proportional to the content of HPMC K4M. The optimized porous film (F4) showed an in vitro drug release of 84.47 ± 0.98%, ex vivo mucoadhesive force of 0.24 ± 0.04 N, and ex vivo mucoadhesion time of 539.11 ± 3.05 min, while the nonporous film (NF4) with the same polymer composition showed a release of 62.66 ± 0.87%, mucoadhesive force of 0.20 ± 0.05 N, and mucoadhesive time of 510 ± 2.00 min. The porous film showed significant differences for drug release and mucoadhesion time (p < 0.05) versus the nonporous film. The mechanism of drug release was observed to follow non-Fickian diffusion (0.1 < n < 0.5) for both porous and nonporous films. Ex vivo permeation studies through chicken buccal mucosa indicated improved drug permeation in porous films versus nonporous films. The present investigation established porous films to be a cost-effective buccoadhesive delivery system of glibenclamide.KEY WORDS: buccoadhesive drug delivery, glibenclamide, in vitro release and ex vivo permeation, porous film 相似文献
11.
Supriya S. Shidhaye Pritesh V. Thakkar Neha M. Dand Vilasrao J. Kadam 《AAPS PharmSciTech》2010,11(1):416-424
The purpose of this study was to develop and optimize formulations of mucoadhesive bilayered buccal tablets of pravastatin sodium using carrageenan gum as the base matrix. The tablets were prepared by direct compression method. Polyvinyl pyrrolidone (PVP) K 30, Pluronic® F 127, and magnesium oxide were used to improve tablet properties. Magnesium stearate, talc, and lactose were used to aid the compression of tablets. The tablets were found to have good appearance, uniform thickness, diameter, weight, pH, and drug content. A 23 full factorial design was employed to study the effect of independent variables viz. levels of carrageenan gum, Pluronic F 127 and PVP K30, which significantly influenced characteristics like in vitro mucoadhesive strength, in vitro drug release, swelling index, and in vitro residence time. The tablet was coated with an impermeable backing layer of ethyl cellulose to ensure unidirectional drug release. Different penetration enhancers were tried to improve the permeation of pravastatin sodium through buccal mucosa. Formulation containing 1% sodium lauryl sulfate showed good permeation of pravastatin sodium through mucosa. Histopathological studies revealed no buccal mucosal damage. It can be concluded that buccal route can be one of the alternatives available for the administration of pravastatin sodium. 相似文献
12.
Surya N. Ratha Adhikari Bhabani S. Nayak Amit K. Nayak Biswaranjan Mohanty 《AAPS PharmSciTech》2010,11(3):1038-1044
Buccal patches for the delivery of atenolol using sodium alginate with various hydrophilic polymers like carbopol 934 P, sodium
carboxymethyl cellulose, and hydroxypropyl methylcellulose in various proportions and combinations were fabricated by solvent
casting technique. Various physicomechanical parameters like weight variation, thickness, folding endurance, drug content,
moisture content, moisture absorption, and various ex vivo mucoadhesion parameters like mucoadhesive strength, force of adhesion, and bond strength were evaluated. An in vitro drug release study was designed, and it was carried out using commercial semipermeable membrane. All these fabricated patches
were sustained for 24 h and obeyed first-order release kinetics. Ex vivo drug permeation study was also performed using porcine buccal mucosa, and various drug permeation parameters like flux and
lag time were determined. 相似文献
13.
Sirpa Vuorinen Jyrki Heinämäki Osmo Antikainen Mohammed Lahcini Timo Repo Jouko Yliruusi 《AAPS PharmSciTech》2009,10(2):566-573
Sugar end-capped poly-d,l-lactide (SPDLA) polymers were investigated as a potential release controlling excipient in oral sustained release matrix
tablets. The SPDLA polymers were obtained by a catalytic ring-opening polymerization technique using methyl α-d-gluco-pyranoside as a multifunctional initiator in the polymerization. Polymers of different molecular weights were synthesized
by varying molar ratios of monomer/catalyst. The matrix tablets were prepared by direct compression technique from the binary
mixtures of SPDLA and microcrystalline cellulose, and theophylline was used as a model drug. The tablet matrices showed in vitro reproducible drug release profiles with a zero-order or diffusion-based kinetic depending on the SPDLA polymer grade used.
Further release from the tablet matrices was dependent on the molecular weight of the SPDLA polymer applied. The drug release
was the fastest with the lowest molecular weight SPDLA grade, and the drug release followed zero-order rate. With the higher
molecular weight SPDLAs, more prolonged dissolution profiles for the matrix tablets (up to 8–10 h) were obtained. Furthermore,
the prolonged drug release was independent of the pH of the dissolution media. In conclusion, SPDLAs are a novel type of drug
carrier polymers applicable in oral controlled drug delivery systems. 相似文献
14.
The aim of this work was to study the influence of β-cyclodextrin (β-CD) on the biopharmaceutic properties of diclofenac (DCF).
To this purpose the physicochemical characterization of diclofenac-β-cyclodextrin binary systems was performed both in solution
and solid state. Solid phase characterization was performed using differential scanning calorimetry (DSC), powder x-ray diffractometry
(XRD), and Fourier transform infrared spectroscopy (FTIR). Phase solubility analyses, and in vitro permeation experiments
through a synthetic membrane were performed in solution. Moreover, DCF/β-CD interactions were studied in DMSO by1H nuclear magnetic resonance (NMR) spectroscopy. The effects of different preparation methods and drug-to-β-CD molar ratios
were also evaluated. Phase solubility studies revealed 1∶1 M complexation of DCF when the freeze-drying method was used for
the preparation of the binary system. The true inclusion for the freeze-dried binary system was confirmed by1H NMR spectroscopy, DSC, powder XRD, and IR studies. The dissolution study revealed that the drug dissolution rate was improved
by the presence of CDs and the highest and promptest release was obtained with the freeze-dried binary system. Diffusion experiments
through a silicone membrane showed that DCF diffusion was higher from the saturated drug solution (control) than the freeze-dried
inclusion complexes, prepared using different DCF-β-CD molar ratios. However, the presence of the inclusion complex was able
to stabilize the system giving rise to a more regular diffusion profile.
Published: October 22, 2005 相似文献
15.
Evidence for NO-dependent vasodilation in the trout (Oncorhynchus mykiss ) coronary system 总被引:1,自引:0,他引:1
T. Mustafa C. Agnisola J. K. Hansen 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1997,167(2):98-104
The effects of l-arginine, and its analogues N
ω-nitro-l-arginine methyl ester and N
ω-nitro-l-arginine on vascular resistance were investigated in the intact coronary system of an isolated non-working trout heart preparation.
l-Arginine, at 10–8 mol · l–1induced a slight vasodilatory effect (max 10%). N
ω-nitro-l-arginine methyl ester and N
ω-Nitro-l-arginine in the range 10–8–10–4 mol · l–1 caused dose-dependent increases in coronary resistance. The vasodilatory action of l-arginine was abolished when the preparation was pretreated with 10–4 mol · l–1
N
ω-nitro-l-arginine or N
ω-nitro-l-arginine methyl ester. Nitroprusside alone at 1 mmol · l–1 induced a maximum vasodilation (30%) of the coronary system. Methylene blue a known inhibitor of guanylate cyclase, induced
a strong vasoconstriction (already significant at 10–5 mol · l–1) and was able to overcome the vasodilative effect of nitroprusside. The endothelial nitric oxide agonists acetylcholine and
serotonin, established in mammalian vessels, also mediate vasodilation in trout coronary system. In 50% of preparations, acetylcholine
induced a biphasic response with vasodilation at low concentration (max 15% at 10–8 mol · l–1). Serotonin displayed a dose-response vasodilation in the range 10–8–10–4 mol · l–1 (max 20%). These vasodilative effects were reduced or abolished by 10–4 mol · l–1
l-NA. These data support the existence of NO-mediated vasodilation mechanisms in the trout coronary system.
Accepted: 1 July 1996 相似文献
16.
Growth of alkaliphilic Bacillus halodurans C-125 both on agar plates and in liquid culture was inhibited by methyl-β-cyclodextrin (CD). Furthermore, resting cells of
the strain were lysed by contact with methyl-β-CD higher than 10 mM. α-CD also showed lysis activity against Bacillus and related strains. The activity was not observed with Gram-negative and Gram-positive bacteria except for Bacillus strains. Fluorescence staining and scanning electron microscopy of cells revealed that methyl-β-CD disrupted cell membranes,
and consequently, the cells were lysed. This is a novel physiological property of CDs. 相似文献
17.
This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 32 factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.KEY WORDS: buspirone HCL, casting/freeze-drying technique, chitosan, cup and core sponge, mucoadhesive buccal sponges 相似文献
18.
Hong E Larios F Gómez-Viquez NL Huang F Bravo G 《Journal of physiology and biochemistry》2011,67(3):427-435
The contribution of α-adrenoceptors and nitric oxide (NO) on the alterations of sympathetically mediated cardiovascular responses
after acute (AcH) and chronic (ChH) hypertension was evaluated in pithed aortic coarcted hypertensive rats. Pressor and tachycardia
response produced by electrical stimulation of preganglionic sympathetic fibers or exogenous noradrenaline (NA) were recorded
in the absence and presence of prazosin (α1-antagonist), rauwolscine (α2-antagonist), or N
G-nitro-l-arginine methyl ester (l-NAME; an inhibitor of NO synthase). Compared with age-matched sham-operated rats (Nt), the pressor response produced by electrical
stimulation or NA was smaller in AcH rats and larger in ChH rats. Prazosin caused a decrease of pressor response elicited
by electrical stimulation or NA in all groups. However, this effect was higher in ChH. Rauwolscine produced a similar increase
of sympathetically mediated pressor response in Nt and AcH rats. Nevertheless, this antagonist did not affect the sympathetically
mediated pressor response in ChH rats. In addition, rauwolscine did not affect the NA-induced pressor response in all groups.
The pressor response elicited by l-NAME was larger in all groups compared without l-NAME and in presence of l-arginine. Moreover, l-NAME in the presence of NA increased sympathetically mediated pressor response is in all groups, compared without it or in
the presence of l-arginine. Compared with Nt, basally produced NO in aortic rings was increased in AcH but decreased in ChH. Collectively,
our data suggest that decreased cardiovascular reactivity in AcH is due to an increase in basally produced NO. In ChH, enhanced
cardiovascular response appears to be associated with a decrease in produced NO and an increase in released NA from sympathetic
nerves. 相似文献
19.
Sosnowski P Krauss H Bogdanski P Suliburska J Jablecka A Cieslewicz A Pupek-Musialik D Jastak R 《Journal of physiology and biochemistry》2012,68(1):1-9
Due to the complex mechanisms of l-arginine activity, it is difficult to determine the clinical significance of supplementation with this amino acid. The objective
of this study was to determine the influence of short-term supplementation with l-arginine in stress conditions, induced by ischemia–reperfusion syndrome, by assessing the damage to muscular and hepatic
cells on the basis of creatine kinase (CK), alanine aminotransferase (ALAT) and aspartic aminotransferase (AspAT) activity
in blood and the level of oxygen free radicals in analyzed tissues of rats. We observed that induced ischemia of hind limb
caused an increase in CK, ALAT and AspAT activity and an increase in the level of free radicals in liver, but not in skeletal
muscle. Supplementation with l-arginine led to a reduction in serum activity of CK and AspAT and reduction of the level of free radicals in analysed tissues.
Simultaneous supplementation with l-arginine AND l-NAME resulted in a reversal of changes induced by l-arginine supplementation in the case of AspAT and free radicals in skeletal muscle. The results indicate that under conditions
of ischemia–reperfusion, short-term administration of l-arginine has a protective effect on skeletal muscle manifesting itself by reduction of CK in the serum and reduction of free
radicals level in THIS tissue. 相似文献
20.
Wei SP Li XQ Chou CF Liang YY Peng JB Warnock DG Ma HP 《The Journal of membrane biology》2007,220(1-3):21-31
We used patch-clamp techniques and A6 distal nephron cells as a model to determine how cholesterol regulates the renal epithelial
sodium channel (ENaC). We found that luminal methyl-β-cyclodextrin (mβCD, a cholesterol scavenger) did not acutely affect
ENaC activity at a previously used concentration of 10 mm but significantly decreased ENaC activity both when the cell membrane was stretched and at a higher concentration of 50 mm. Luminal cholesterol had no effect on ENaC activity at a concentration of 50 μg/ml but significantly increased ENaC activity
both when the cell membrane was stretched and at a higher concentration of 200 μg/ml. Confocal microscopy data indicate that
membrane tension facilitates both mβCD extraction of cholesterol and A6 cell uptake of exogenous cholesterol. Together with
previous findings that cholesterol in the apical membrane is tightly packed with sphingolipids and that stretch can affect
lipid distribution, our data suggest that membrane tension modulates the effects of mβCD and cholesterol on ENaC activity,
probably by facilitating both extraction and enrichment of apical cholesterol. 相似文献