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1.
In this study, we are reporting antileishmanial activity of a marine sponge Haliclona exigua, belonging to phylum Porifera. The crude methanol extract and its three fractions were tested both in vitro and in vivo.
The crude extract exerted almost complete inhibition of promastigotes at 50 μg/ml and 76.4 ± 6.5% inhibition of intracellular
amastigotes at 100 μg/ml concentration with IC50 values of 18.6 μg/ml and 47.2 μg/ml, respectively. When administered to Leishmania donovani infected hamsters at a dose of 500 mg/kg × 5, p.o., it resulted in 72.2 ± 10.4% inhibition of intracellular amastigotes.
At a lower dose (250 mg/kg), it exhibited 43.9 ± 5.1% inhibition. Among the fractions, highest antileishmanial activity both
in vitro (>90%) and in vivo (60.9 ± 18.3%) was observed in n-butanol (soluble) fraction with IC50 values of 8.2 μg/ml and 31.2 μg/ml against promastigotes and intracellular amastigotes, respectively. Hexane fraction also
showed comparatively good activity against both the stages of parasites in vitro but was moderately active in leishmania-infected
hamsters. Chloroform fraction resulted in 45 ± 10.2% inhibition in vivo at a dose of 500 mg/kg × 5, p.o., whereas it was inactive
in vitro. n-Butanol (insoluble) fraction was inactive both in vitro and in vivo. Araguspongin C, an alkaloid isolated from n-butanol (soluble) fraction exhibited moderate inhibition of promastigotes and intracellular amastigotes at 100 μg/ml but
showed weak antileishmanial action in vivo. Our findings indicate that this marine sponge has the potential to provide new
lead toward development of an effective antileishmanial agent and, hence, calls for more exhaustive studies for exploiting
the vast world of marine resources to combat the scourge of several parasitic diseases. 相似文献
2.
Pujals G Suñé-Negre JM Pérez P García E Portus M Tico JR Miñarro M Carrió J 《Parasitology research》2008,102(6):1243-1247
The aim of the present study was to evaluate the in vitro activity and cytotoxicity of meglumine antimoniate microspheres
produced by spray drying on Leishmania infantum and the effect of the excipients used in them. The parasite strain shows sensitivity to the meglumine antimoniate microspheres
prepared. All the antimony IC50 values from encapsulated meglumine antimoniate (3.80 ± 0.34 to 9.53 ± 0.70 μg SbV/ml for promastigotes assay) are considerably
lower compared to the mean value of IC50 in Glucantime solution (112 ± 12.74 μg SbV/ml). Interesting IC50 values for the excipient chitosan (112.64 ± 0.53 mg/ml for promastigotes and 100.81 ± 26.45 mg/ml for amastigotes) were obtained
(without cytotoxic activity), whereas the rest of the excipients did not show any activity. This new delivery system could
offer a new pharmacological tool for the treatment of leishmaniosis that reduces the doses required, lowering toxic side effects
because of meglumine antimoniate. 相似文献
3.
The leishmanicidal activity of Aloe vera leaf exudate (AVL) has been demonstrated in promastigotes and axenic amastigotes, but its effectiveness in animal models
has not been evaluated. The presence of alkaloids, triterpenes, cyanidines, proanthocyanidines, tannins, and saponins in AVL
was identified. Its effectiveness in four Leishmania donovani strains was studied both in promastigotes (IC50 ranged from 70–115 μg/ml) and amastigotes (IC50 ranged from 3.1–11.4 μg/ml). In amastigotes, the killing by AVL was facilitated through its induction of nitric oxide in
leishmania-infected macrophages. The safety index was good as AVL up to 300 μg/ml remained non-toxic to monocytes and macrophages. In
a L. donovani BALB/c mouse model, oral or subcutaneous administration of AVL (15 mg/kg body weight × 5 days) reduced parasitemia by >90%
in the liver, spleen, and bone marrow without impairment of hepatic and renal functions. Collectively, we conclude that AVL
shows promising antileishmanial activity and may provide a new lead agent in the treatment of Leishmaniasis.
Chitra Mandal and Mitali Chatterjee should be considered as joint senior authors. 相似文献
4.
Moreno D Plano D Baquedano Y Jiménez-Ruiz A Palop JA Sanmartín C 《Parasitology research》2011,108(1):233-239
In the present study, a family of 15 imidothio- and imidoselenocarbamates (1–15) analogs have been synthesized and screened
for their in vitro antileishmanial potential against Leishmania infantum promastigotes. The six most active ones (2, 4, 7, 13, 14, and 15) were also tested in an axenic amastigote model. In order
to establish their selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1
cell lines. Compounds 2 and 4, both with a pyridine moiety, showed a moderate antileishmanial activity with an IC50 value of 4.68 ± 0.46 and 3.03 ± 0.24 μM, respectively, in the amastigote model. The activity was compared with that of standard
drugs, edelfosine (IC50 = 0.82 ± 0.13 μM) and miltefosine (IC50 = 2.84 ± 0.10 μM). Related to selectivity, the SI of both compounds are similar to those of the standard drugs when compared
against the THP-1 cell line. Moreover, compound 4 was able to reduce the number of amastigote-infected THP-1 cells to 40%
of that observed in untreated controls after a 96-h period of treatment. These derivatives thus represent two new leads for
further studies aimed at establishing their mechanism of action. 相似文献
5.
Passero LF Tomokane TY Corbett CE Laurenti MD Toyama MH 《Parasitology research》2007,101(5):1365-1371
In this study, we compared the anti-leishmanial activity of three crotalic venoms (Crotalus durissus terrificus–Cdt, Crotalus durissus cascavella–Cdca, and Crotalus durissus collilineatus–Cdcol). Different concentrations of each venom incubated with Leishmania (Leishmania) amazonensis promastigotes were used. Cdt venom exhibited a higher anti-leishmanial activity (Inhibitory concentration-IC50-value of 4.70 ± 1.72 μg/ml) in comparison
with that of Cdca venom (IC50 value of 9.41 ± 1.21 μg/ml), while Cdcol venom increased parasite numbers in 50% at a concentration of 44.30 ± 2.18 μg/ml. In addition, this venom showed a low anti-leishmanial
activity in higher concentrations (IC50 value of 281.00 ± 9.50 μg/ml). The main fractions of Cdca venom were isolated and assayed under similar conditions used for assessing crude venom. The most active fractions were gyroxin
and crotamine that had IC50 values of 3.80 ± 0.52 μg/ml and 19.95 ± 4.21 μg/ml, respectively. Convulxin also inhibited parasite
growth rate, although this effect was not dose-dependent. Crotoxin was the least effective fraction with an IC50 value of
99.80 ± 2.21 μg/ml. None of the protein fractions presented cytotoxic effects against J774 cells in culture. In vivo assays
using BALB/c mice revealed that crotoxin and crotamine were the main toxic fractions. In conclusion, C. durissus cascavella venom has three main fractions with anti-leishmanial activity. These results open new possibilities to find proteins that
might be used as possible agents against cutaneous leishmaniasis. 相似文献
6.
Polanco-Hernández G Escalante-Erosa F García-Sosa K Acosta-Viana K Chan-Bacab MJ Sagua-Franco H González J Osorio-Rodríguez L Moo-Puc RE Peña-Rodríguez LM 《Parasitology research》2012,110(1):31-35
Ethanol extracts of Senna villosa, Serjania yucatanensis, Byrsonima bucidaefolia, and Bourreria pulchra were evaluated for their in vitro activity against epimastigotes and trypomastigotes of Trypanosoma cruzi. Results showed that the leaf extracts of S. yucatanensis and B. pulchra were the most active against epimastigotes (IC100 = 100 μg/mL) and trypomastigotes of T. cruzi (95% or more reduction in the number of parasites at 100 and 50 μg/mL). However, only the leaf extract of S. yucatanensis showed significant trypanocidal activity when tested in vivo, reducing 75% of the parasitemia in infected mice at 100 mg/kg.
This same extract inhibited the egress of trypomastigotes from infected cells and proved not to be cytotoxic (IC50 = 318.8 ± 2.3 μg/mL). 相似文献
7.
Passero LF Castro AA Tomokane TY Kato MJ Paulinetti TF Corbett CE Laurenti MD 《Parasitology research》2007,101(3):677-680
The crude methanolic extract from leaves of Jacaranda puberula showed activity against Leishmania (Leishmania) amazonensis. The extract presented active against promastigote forms with an inhibitory concentration 50% (IC50) value of 88.0 μg/ml, but only moderated activity against amastigote forms; however in higher concentrations the extract
showed cytotoxic effects. The bio-guided chromatographic fractionation the crude methanolic extract against amastigotes yielded
a fraction with an IC50 value of 14.0 μg/ml (without cytotoxic activity) in relation to the crude extract (IC50 value, 359.0 μg/ml). These data indicate that J. puberula leaves contain active compounds, which should be further investigated for the development of new potential drugs against
cutaneous leishmaniasis. 相似文献
8.
Moon HI 《Parasitology research》2007,100(5):1147-1149
Samples of Carpesium genus used as traditional remedies for the treatment of parasite infections were collected, and methanol extracts were obtained
by sonication. The ethylacetate-, n-butanol- and H2O-soluble fractions exhibited weak antiplasmodial activity (IC50 > 100 μg/ml; IC50, 50% inhibitory concentration). However, the chloroform fraction exhibited more impressive antiplasmodial activity (IC50 = 8.2 μg/ml). The antiplasmodial activity of the chloroform fractions was evaluated in vitro against the chloroquine-resistant
D10 strain of Plasmodium falciparum. Bioactivity-guided isolation of the chloroform fractions of the whole plants of Carpesium rosulatum has led to the isolation of a sesquiterpene lactone, ineupatorolides A, displaying high antiplasmodial activity (IC50 = 0.007 μg/ml). This is the first report of the isolation of ineupatorolides A from this species and of its remarkable antiplasmodial
activity. 相似文献
9.
In order to assess the potential of the stem bark of Kigelia africana (Lam.) Benth as source of new anti-malarial leads, n-hexane and ethyl acetate (EtOAc) extracts and four compounds isolated
from the stem bark were screened in vitro against the chloroquine-resistant W-2 and two field isolates of Plasmodium falciparum using lactate dehydrogenase assay. The products were also tested for their cytotoxicity on LLC/MK2 monkey kidney cells. The
EtOAc extract exhibited a significant antiplasmodial activity (IC50 = 11.15 μg/mL on W-2; 3.91 and 4.74 μg/mL on field CAM10 and SHF4 isolates, respectively), whereas the n-hexane fraction
showed a weak activity (IC50 = 73.78 μg/mL on W-2 and 21.85 μg/mL on SHF4). Three out of the four compounds showed good activity against all the three
different parasite strains (IC50 < 5 μM). Specicoside exhibited the highest activity on W-2 (IC50 = 1.54 μM) followed by 2β, 3β, 19α-trihydroxy-urs-12-en-28-oic acid (IC50 = 1.60 μM) and atranorin (IC50 = 4.41 μM), while p-hydroxycinnamic acid was the least active (IC50 = 53.84 μM). The EtOAc extract and its isolated compounds (specicoside and p-hydroxycinnamic acid) were non-cytotoxic (CC50 > 30 μg/mL), whereas the n-hexane extract and two of its products, atranorin and 2β, 3β, 19α-trihydroxy-urs-12-en-28-oic
acid showed cytotoxicity at high concentrations, with the last one being the most toxic (CC50 = 9.37 μg/mL). These findings justify the use of K. africana stem bark as antimalaria by traditional healers of Western Cameroon, and could constitute a good basis for further studies
towards development of new leads or natural drugs for malaria. 相似文献
10.
For decades, drug resistance has been the major obstacle in the fight against malaria, and the search for new drugs together
with the combination therapy constitutes the major approach in responding to this situation. The present study aims at assessing
the in vitro antimalarial activity of four compounds isolated from Kigelia africana stem bark (atranorin - KAE1, specicoside - KAE7, 2β,3β,19α-trihydroxy-urs-12-20-en-28-oic acid – KAE3, and p-hydroxy-cinnamic acid – KAE10) and their drug interactions among themselves and their combination effects with quinine and
artemether. The antiplasmodial activity and drug interactions were evaluated against the multidrug-resistant W2mef strain
of Plasmodium falciparum using the parasite lactate dehydrogenase assay. Three of the four compounds tested were significantly active against W2mef:
specicoside (IC50 = 1.02 ± 0.17 μM), 2β,3β,19α-trihydroxy-urs-12-en-28-oic acid (IC50 = 1.86 ± 0.15 μM) and atranorin (IC50 = 1.78 ± 0.18 μM), whereas p-hydroxy-cinnamic acid showed a weak activity (IC50 = 12.89 ± 0.87 μM). A slight synergistic effect was observed between atranorin and 2β,3β,19α-trihydroxy-urs-12-en-28-oic
acid (Combination index, CI = 0.82) whereas the interaction between specicoside and p-hydroxy-cinnamic acid were instead antagonistic (CI = 2.67). All the three compounds showed synergistic effects with artemether,
unlike the slight antagonistic interactions of atranorin and 2β,3β,19α-trihydroxy-urs-12-en-28-oic acid in combination with
quinine. K. africana compounds are therefore likely to serve as leads in the development of new partner drugs in artemether-based combination
therapy. 相似文献
11.
In the present investigation, we have evaluated the antileishmanial and antitrypanosomal activity of methanolic crude extracts
obtained from eight species of cnidarians and of a modified steroid isolated from the octocoral Carijoa riisei. The antileishmanial activity of cnidarians crude extracts showed 50% inhibitory concentration (IC50) values in the concentration range between 2.8 and 93.3 μg/mL. Trypomastigotes of Trypanosoma cruzi were less susceptible to the crude extracts, with IC50 values in the concentration range between 40.9 and 117.9 μg/mL. The steroid (18-acetoxipregna-1,4,20-trien-3-one) displayed
a strong antileishmanial activity, with an IC50 value of 5.5 μg/mL against promastigotes and 16.88 μg/mL against intracellular amastigotes. The steroid also displayed mammalian
cytotoxicity (IC50 of 10.6 μg/mL), but no hemolytic activity was observed at the highest concentration of 12.5 μg/mL. The antileishmanial effect
of the steroid in macrophages suggested other mechanism than macrophage activation, as no upregulation of nitric oxide was
observed. The antitrypanosomal activity of the steroid resulted in an IC50 value of 50.5 μg/mL. These results indicate the potential of cnidarian natural compounds as antileishmanial drug candidates. 相似文献
12.
Shuaibu MN Wuyep PA Yanagi T Hirayama K Tanaka T Kouno I 《Parasitology research》2008,102(6):1119-1127
In vitro antiplasmodial activity of methanolic extracts of 16 medicinal plants was evaluated by fluorometric assay using PicoGreen.
The IC50s, as determined by parasite DNA concentration, ranged from <11 to >200 and <13 to >200 μg/ml for Plasmodium falciparum 3D7 and K1, respectively; and the most active extracts were those from Anogeissus leiocarpus and Terminalia avicennoides (<11–≥14 μg/ml). Aqueous, butanolic, ethyl acetate, and methanolic fractions of these two extracts revealed butanolic fraction
to have a relatively better activity (IC50, 10–12 μg/ml). Activity-guided chromatographic separation of the butanolic fraction on Sephadex LH-20 followed by nuclear
magnetic resonance and correlation high-performance liquid chromatography revealed the presence of known hydrolysable tannins
and some related compounds—castalagin, ellagic acid, flavogallonic acid, punicalagin, terchebulin, and two other fractions.
The IC50s of all these compounds ranged between 8–21 μg/ml (8–40 μM) against both the strains. Toxicity assay with mouse fibroblasts
showed all the extracts and isolated compounds to have IC50 ≥ 1500 μg/ml, except for Momordica balsamina with <1500 μg/l. All the extracts and isolated compounds did not affect the integrity of human erythrocyte membrane at the
observed IC50s. However, adverse effects manifest in a concentration-dependent fashion (from IC50 ≥ 500 μg/ml). 相似文献
13.
Susana Méndez Francisco José Fernández-Pérez Concepción de la Fuente Montserrat Cuquerella María Teresa Gómez-Muñoz José María Alunda 《Parasitology research》1999,85(6):507-509
Leishmania infantum stationary-phase promastigotes could acquire infectivity via preincubation in a partially anaerobic medium (95% air/5% CO2) for 16 h before the infection, whereas promastigotes were efficiently destroyed when no CO2 was present. Incubation of L. infantum promastigotes with additional glucose (20 and 50 mM) greatly increased infection parameters in the absence of CO2; this is consistent with a “reverse Pasteur effect.” Results showed that culture at 33 °C permitted survival and amastigote
multiplication (a nearly 10-fold increase in amastigotes as compared with those observed in 37 °C cultures). This finding
was obtained with the two strains of L. infantum tested (Doba and PB75).
Received: 28 November 1998 / Accepted: 17 December 1998 相似文献
14.
Santoro GF das Graças Cardoso M Guimarães LG Salgado AP Menna-Barreto RF Soares MJ 《Parasitology research》2007,100(4):783-790
In the present work, we have investigated the effect of essential oils obtained from Origanum vulgare L. (oregano) and Thymus vulgaris L. (thyme) on growth and ultrastructure of diverse evolutive forms of Trypanosoma cruzi. Culture epimastigotes and bloodstream trypomastigotes were incubated for 24 h with different concentrations of oregano or
thyme essential oils and with thymol (the main constituent of thyme), and the inhibitory concentration (IC)50 was determined by cell counting. Crude extract of oregano essential oil inhibited epimastigote growth (IC50/24 h = 175 μg/ml) and also induced trypomastigote lysis (IC50/24 h = 115 μg/ml). Thyme essential oil presented IC50/24 h values of 77 μg/ml for epimastigotes and 38 μg/ml for trypomastigotes, while treatment with thymol resulted in an IC50/24 h of 62 μg/ml for epimastigotes and 53 μg/ml for trypomastigotes. Scanning electron microscopy of treated cells showed
few morphological alterations at the plasma membrane. Observation by transmission electron microscopy showed cytoplasmic swelling
with occasional morphological alterations in plasma and flagellar membrane. Our data indicate that oregano and thyme essential
oils are effective against T. cruzi, with higher activity of thyme, and that thymol may be the main component responsible for the trypanocidal activity. 相似文献
15.
Almassy J Sztretye M Lukacs B Dienes B Szabo L Szentesi P Vassort G Csernoch L Jona I 《Pflügers Archiv : European journal of physiology》2008,457(1):171-183
The benzothiazepine derivative K-201 has been suggested as a potential therapeutic agent due to its antiarrhythmogenic action.
To understand how the drug alters calcium release from the sarcoplasmic reticulum (SR), we investigated its effects on the
SR calcium channel and calcium pump by single channel electrophysiology, whole-cell confocal microscopy, and ATPase activity
measurements on control and post-myocardial infarcted (PMI) rat skeletal muscle. In bilayers, K-201 induced two subconductance
states corresponding to ∼24% (S1) and ∼13% (S2) of the maximum conductance. Dependence of event frequency and of time spent in S1 and S2 on the drug concentration was biphasic both in control and in PMI rats, with a maximum at 50 μM. At this concentration, the
channel spends 26 ± 4% and 24 ± 4%, respectively, of the total time in these subconductance states at positive potentials,
while no subconductances are observed at negative potentials. K-201 altered the frequency of elementary calcium release events:
spark frequency decreased from 0.039 ± 0.001 to 0.023 ± 0.001 s−1 sarcomere−1, while the frequency of embers increased from 0.011 ± 0.001 to 0.023 ± 0.001 s−1 sarcomere−1. Embers with different amplitude levels were observed after the addition of the drug. K-201 inhibited the Ca2+ ATPase characterized by IC50,contr = 119 ± 21 μM and n
Hill,contr = 1.84 ± 0.48 for control and IC50,PMI = 122 ± 18 μM and n
Hill,PMI = 1.97 ± 0.24 for PMI animals. These results suggest that although K-201 would increase the appearance of subconductance
states, the overall calcium release is reduced by the drug. In addition, the effect of K-201 is identical on calcium release
channels from control and PMI rats. 相似文献
16.
A new colourimetric method to be used for the screening of compounds with giardicidal activity was developed. After the end
of drug incubation, the remaining viable cells were fixed with methanol and stained by methylene blue. The inclusion of methylene
blue by Guardia lamblia trophozoites was measured spectrophotometrically to determine the anti-giardial activity of metronidazole. The 50% inhibitory
concentration (IC50) was 1.96 ± 0.13 μM. The reliability of this method was assessed by comparison with the IC50 obtained using a haemocytometer to get the number of viable cells (1.82 ± 0.43 μM). This method provides a feasible, cheap
and reliable method to determine the anti-giardial activity of drugs. 相似文献
17.
Bagavan A Rahuman AA Kamaraj C Kaushik NK Mohanakrishnan D Sahal D 《Parasitology research》2011,108(5):1099-1109
The absence of a vaccine and the rampant resistance to almost all antimalarial drugs have accentuated the urgent need for
new antimalarial drugs and drug targets for both prophylaxis and chemotherapy. The aim of the study was to discover effective
plant extracts against Plasmodium falciparum. In the present study, the hexane, chloroform, ethyl acetate, acetone, and methanol extracts of Citrus sinensis (peel), Leucas aspera, Ocimum sanctum, Phyllanthus acidus (leaf), Terminalia chebula (seed) were tested for their antimalarial activity against chloroquine (CQ)-sensitive (3D7) strain of P. falciparum which was cultured following the candle-jar method. Antimalarial evaluations of daily replacement of culture medium containing
CQ and different plant crude extracts were performed on 96-well plates at 37°C for 24 and 48 h. Parasitemia was determined
microscopically on thin-film Giemsa-stained preparations. Plant extracts were tested for their cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
tetrazolium bromide (MTT) assay on human laryngeal cancer cell line (HEp-2) and normal cell line (Vero). Out of the 25 extracts
tested, six showed good (IC50 4.76–22.76 μg/mL), 15 exhibited moderate (IC50 31.42–88.03 μg/mL), while four displayed mild (IC50 > 100 μg/mL) antiplasmodial activity. The leaf ethyl acetate and methanol extracts of L. aspera; ethyl acetate, acetone, and methanol extracts of P. acidus; and seed acetone extract of T. chebula had good antiplasmodial activity (IC50 = 7.81, 22.76, 9.37, 14.65, 12.68, and 4.76 μg/mL) with selectivity indices 5.43, 2.04, 4.88, 3.35, 3.42, and 9.97 for HEp-2
and >5.79, >2.20, >11.75, >3.41, >3.94, and >7.38 for Vero cells, respectively. These analyses have revealed for the first
time that the components present in the solvent extracts of L. aspera, P. acidus, and T. chebula have antiplasmodial activity. The high antiplasmodial activity observed make these plants good candidates for isolation of
anti-protozoal compounds which could serve as new lead structures for drug development. 相似文献
18.
Mehmet Ali Altintas A. A. Altintas M. Guggenheim A. E. Steiert M. C. Aust A. D. Niederbichler C. Herold P. M. Vogt 《Journal of digital imaging》2010,23(4):475-481
Reflectance-mode confocal laser scanning microscopy allows in vivo imaging of the human skin. We hypothesized that this high-resolution
technique enables observation of dynamic changes of the cutaneous microcirculation. Twenty-two volunteers were randomly divided
in two groups. Group 1 was exposed to local heating and group 2 to local cold stress. Confocal microscopy was performed prior
t
0 (control), directly t
1 and 5 min t
2 after local temperature changes to evaluate quantitative blood cell flow, capillary loop diameter, and density of dermal
capillaries. In group 1, blood flow increased at t
1 (75.82 ± 2.86/min) and further at t
2 (84.09 ± 3.39/min) compared to the control (61.09 ± 3.21/min). The control capillary size was 9.59 ± 0.25 μm, increased to
11.16 ± 0.21 μm (t
1) and 11.57 ± 0.24 μm (t
2). The dermal capillary density increased in t
1 (7.26 ± 0.76/mm2) and t
2 (8.16 ± 0.52/mm2), compared to the control (7.04 ± 0.62/mm2). In group 2, blood flow decreased at t
1 (41.73 ± 2.61/min) and increased at t
2 (83.27 ± 3.29/min) compared to the control (60.73 ± 2.90/min). The control capillary size was 9.55 ± 0.25 μm, decreased at
t
1 (7.78 ± 0.26 μm) and increased at t
2 (11.38 ± 0.26 μm). Capillary density decreased at t
1 (5.01 ± 0.49/mm2) and increased at t
2 (7.28 ± 0.53/mm2) compared to the control (7.01 ± 0.52/mm2). Confocal microscopy is a sensitive and noninvasive imaging tool for characterizing and quantifying dynamic changes of cutaneous
microcirculation on a histomorphological level. 相似文献
19.
Mitochondrial Ca2+ plays important roles in the regulation of energy metabolism and cellular Ca2+ homeostasis. In this study, we characterized mitochondrial Ca2+ accumulation in Syrian hamster hearts with hereditary cardiomyopathy (strain BIO 14.6). Exposure of isolated mitochondria
from 70 nM to 30 μM Ca2+ ([Ca2+]o) caused a concentration-dependent increase in intramitochondrial Ca2+ concentrations ([Ca2+]m). The [Ca2+]m was significantly lower in cardiomyopathic (CMP) hamsters than in healthy hamsters when [Ca2+]o was higher than 1 μM and a decrease of about 52% was detected at [Ca2+]o of 30 μM (916 ± 67 nM vs 1,932 ± 132 nM in control). A possible mechanism responsible for the decreased mitochondrial Ca2+ uptake in CMP hamsters is the depolarization of mitochondrial membrane potential (Δψ
m). Using a tetraphenylphosphonium (TPP+) electrode, the measured Δψ
m in failing heart mitochondria was −136 ± 1.5 mV compared with −159 ± 1.3 mV in controls. Analyses of mitochondrial respiratory
chain demonstrated a significant impairment of complex I and complex IV activities in failing heart mitochondria. In summary,
a less negative Δψ
m resulting from defects in the respiratory chain may lead to attenuated mitochondrial Ca2+ accumulation, which in turn may contribute to the depressed energy production and myocardial contractility in this model
of heart failure. In addition to other known impairments of ion transport in sarcoplasmic reticulum and plasma membrane, results
from this paper on mitochondrial dysfunctions expand our understanding of the molecular mechanisms leading to heart failure. 相似文献
20.
Matos JE Sorensen MV Geyti CS Robaye B Boeynaems JM Leipziger J 《Pflügers Archiv : European journal of physiology》2007,454(6):977-987
Luminal P2 receptors are ubiquitously expressed in transporting epithelia. In steroid-sensitive epithelia (e.g., lung, distal
nephron) epithelial Na+ channel (ENaC)-mediated Na+ absorption is inhibited via luminal P2 receptors. In distal mouse colon, we have identified that both, a luminal P2Y2 and a luminal P2Y4 receptor, stimulate K+ secretion. In this study, we investigate the effect of luminal adenosine triphosphate/uridine triphosphate (ATP/UTP) on electrogenic
Na+ absorption in distal colonic mucosa of mice treated on a low Na+ diet for more than 2 weeks. Transepithelial electrical parameters were recorded in an Ussing chamber. Baseline parameters:
transepithelial voltage (V
te): −13.7 ± 1.9 mV (lumen negative), transepithelial resistance (R
te): 24.1 ± 1.8 Ω cm2, equivalent short circuit current (I
sc): −563.9 ± 63.8 μA/cm2 (n = 21). Amiloride completely inhibited I
sc to −0.5 ± 8.5 μA/cm2. Luminal ATP induced a slowly on-setting and persistent inhibition of the amiloride-sensitive I
sc by 160.7 ± 29.7 μA/cm2 (n = 12, NMRI mice). Luminal ATP and UTP were almost equipotent with IC50 values of 10 μM and 3 μM respectively. In P2Y2 knock-out (KO) mice, the effect of luminal UTP on amiloride-sensitve Na+ absorption was absent. In contrast, in P2Y4 KO mice the inhibitory effect of luminal UTP on Na+ absorption remained present. Semiquantitative polymerase chain reaction did not indicate regulation of the P2Y receptors
under low Na+ diet, but it revealed a pronounced axial expression of both receptors with highest abundance in surface epithelia. Thus,
luminal P2Y2 and P2Y4 receptors and ENaC channels co-localize in surface epithelium. Intriguingly, only the stimulation of the P2Y2 receptor mediates inhibition of electrogenic Na+ absorption. 相似文献