RESUMO
This study investigates the impacts of exposure to an environment Ca2+ challenge and the mechanism of action of dibutyl phthalate (DBP) on Ca2+ influx in the gills of Danio rerio. In vitro profile of 45Ca2+ influx in gills was verified through the basal time-course. Fish were exposed to low, normal and high Ca2+ concentrations (0.02, 0.7 and 2 mM) for 12 h. So, gills were morphologically analysed and ex vivo45Ca2+ influx at 30 and 60 min was determined. For the in vitro studies, gills were treated for 60 min with DBP (1 pM, 1 nM and 1 µM) with/without blockers/activators of ionic channels, Ca2+ chelator, inhibitors of ATPases, ionic exchangers and protein kinase C to study the mechanism of DBP-induced 45Ca2+ influx. Exposure to high environmental Ca2+ augmented 45Ca2+ influx when compared to fish exposed to normal and low Ca2+ concentrations. Additionally, histopathological changes were observed in the gills of fish maintained for 12 h in low and high Ca2+. In vitro exposure of gills to DBP (1 pM) disturbed Ca2+ homeostasis. DBP stimulated 45Ca2+ influx in gills through the transitory receptor potential vanilloid 1 (TRPV1), and reverse-mode Na+/Ca2+ exchanger (NCX) activation, protein kinase C and K+ channels and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). These data suggest that in vivo short-term exposure of gills to low and high Ca2+ leads to 45Ca2+ influx and histopathological changes. Additionally, the DBP-induced rapid 45Ca2+ influx is mediated by TRPV1, NCX activation with the involvement of PKC, K+-channels and SERCA, thereby altering Ca2+ homeostasis.
Assuntos
Radioisótopos de Cálcio/metabolismo , Cálcio/metabolismo , Dibutilftalato/toxicidade , Brânquias/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Cálcio/toxicidade , Dibutilftalato/metabolismo , Retículo Endoplasmático/metabolismo , Brânquias/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Canais de Cátion TRPV/metabolismo , Poluentes Químicos da Água/metabolismoRESUMO
Formation water (FoW) is a by-product from oil and gas production and usually has high concentrations of soluble salts and metals. Calcium (Ca) and magnesium (Mg) have been shown to reduce the toxicity of metals to aquatic animals, and previous study showed that high waterborne Ca exerts mild effect against disturbances on Na+ regulation in Amazonian armored catfish tamoatá (Hoplosternum littorale) acutely exposed to high Fe, Mn, and Ba levels. Here, we hypothesized that high Mg levels might also reduce the toxic effects of these metals on Na+ regulation of tamoatá. The exposure to 5% FoW promoted an increase in Na+ uptake and a rapid accumulation of Na+ in all tissues analyzed (kidneyAssuntos
Bário/química
, Cálcio/metabolismo
, Peixes-Gato/metabolismo
, Brânquias/metabolismo
, Íons/química
, Magnésio/química
, Sódio/metabolismo
, Poluentes Químicos da Água/análise
, Animais
, Bário/toxicidade
, Cálcio/toxicidade
, Magnésio/toxicidade
, Sódio/química
, Sódio/toxicidade
, Poluentes Químicos da Água/química
RESUMO
The purpose of this paper was to describe obstructive urolithiasis with uroperitoneum and hydronephrosis in range cattle in southern Rio Grande do Sul. The disease was observed in castrated male cattle, aged between 18 months and 3 years in a herd of 200 steers that were in a ryegrass pasture during the winter and a native pasture during the summer. Different mineral salts were used as a supplement for the animals during the two seasons of the year. Cattle presented a progressive abdominal distention, depression and dehydration ranging from 10 days to one month in duration. One animal was necropsied, and approximately 50 liters of urine (uroperitoneum) in the abdominal cavity were observed. The bladder had a small rupture and was adhered to the pelvic cavity. The right kidney was enlarged with hydronephrosis. Uroliths of more than 1cm in diameter were housed in the penile urethra. In this study, the disease occurred probably because of mineral salt supplementation, resulting in an imbalance of calcium and phosphorus intake.(AU)
O objetivo deste trabalho foi descrever urolitíase obstrutiva associada a hidroperitônio e hidronefrose em bovinos no sul do Rio Grande do Sul. A doença foi observada em um rebanho de 200 bovinos machos castrados, com idade entre 18 meses e três anos, mantidos a campo, que permaneciam no inverno em pastagem de azevém e no verão em campo nativo e eram suplementados com diferentes sais minerais nas duas épocas do ano. Os bovinos afetados apresentavam aumento de volume abdominal progressivo, depressão e desidratação, com evolução de 10 dias a um mês. Um bovino foi necropsiado e havia na cavidade abdominal aproximadamente 50 litros de urina (uroperitônio). A bexiga apresentava pequena ruptura e aderência à cavidade pélvica. O rim direito estava aumentado de tamanho e apresentava hidronefrose. Havia urólitos de mais ou menos 1cm de diâmetro alojados na uretra peniana. Neste caso é provável que a doença tenha ocorrido em consequência da suplementação com sal mineral contendo quantidades inadequadas de cálcio e fósforo levando a um desequilíbrio entre estes minerais.(AU)
Assuntos
Animais , Masculino , Bovinos , Urolitíase/veterinária , Hidronefrose/veterinária , Ruminantes/fisiologia , Cálcio/toxicidade , Fósforo/toxicidade , Doenças Urológicas/veterináriaRESUMO
The purpose of this paper was to describe obstructive urolithiasis with uroperitoneum and hydronephrosis in range cattle in southern Rio Grande do Sul. The disease was observed in castrated male cattle, aged between 18 months and 3 years in a herd of 200 steers that were in a ryegrass pasture during the winter and a native pasture during the summer. Different mineral salts were used as a supplement for the animals during the two seasons of the year. Cattle presented a progressive abdominal distention, depression and dehydration ranging from 10 days to one month in duration. One animal was necropsied, and approximately 50 liters of urine (uroperitoneum) in the abdominal cavity were observed. The bladder had a small rupture and was adhered to the pelvic cavity. The right kidney was enlarged with hydronephrosis. Uroliths of more than 1cm in diameter were housed in the penile urethra. In this study, the disease occurred probably because of mineral salt supplementation, resulting in an imbalance of calcium and phosphorus intake.
O objetivo deste trabalho foi descrever urolitíase obstrutiva associada a hidroperitônio e hidronefrose em bovinos no sul do Rio Grande do Sul. A doença foi observada em um rebanho de 200 bovinos machos castrados, com idade entre 18 meses e três anos, mantidos a campo, que permaneciam no inverno em pastagem de azevém e no verão em campo nativo e eram suplementados com diferentes sais minerais nas duas épocas do ano. Os bovinos afetados apresentavam aumento de volume abdominal progressivo, depressão e desidratação, com evolução de 10 dias a um mês. Um bovino foi necropsiado e havia na cavidade abdominal aproximadamente 50 litros de urina (uroperitônio). A bexiga apresentava pequena ruptura e aderência à cavidade pélvica. O rim direito estava aumentado de tamanho e apresentava hidronefrose. Havia urólitos de mais ou menos 1cm de diâmetro alojados na uretra peniana. Neste caso é provável que a doença tenha ocorrido em consequência da suplementação com sal mineral contendo quantidades inadequadas de cálcio e fósforo levando a um desequilíbrio entre estes minerais.
Assuntos
Masculino , Animais , Bovinos , Hidronefrose/veterinária , Ruminantes/fisiologia , Urolitíase/veterinária , Cálcio/toxicidade , Doenças Urológicas/veterinária , Fósforo/toxicidadeRESUMO
BACKGROUND & AIMS: Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release-activated calcium modulator ORAI1 is the most abundant Ca(2+) entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice. METHODS: Mouse and human acinar cells, as well as HEK 293 cells transfected to express human ORAI1 with human stromal interaction molecule 1, were hyperstimulated or incubated with human bile acid, thapsigargin, or cyclopiazonic acid to induce calcium entry. GSK-7975A or CM_128 were added to some cells, which were analyzed by confocal and video microscopy and patch clamp recordings. Acute pancreatitis was induced in C57BL/6J mice by ductal injection of taurolithocholic acid 3-sulfate or intravenous' administration of cerulein or ethanol and palmitoleic acid. Some mice then were given GSK-7975A or CM_128, which inhibit ORAI1, at different time points to assess local and systemic effects. RESULTS: GSK-7975A and CM_128 each separately inhibited toxin-induced activation of ORAI1 and/or activation of Ca(2+) currents after Ca(2+) release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). The ORAI1 inhibitors also prevented activation of the necrotic cell death pathway in mouse and human pancreatic acinar cells. GSK-7975A and CM_128 each inhibited all local and systemic features of acute pancreatitis in all 3 models, in dose- and time-dependent manners. The agents were significantly more effective, in a range of parameters, when given at 1 vs 6 hours after induction of pancreatitis. CONCLUSIONS: Cytosolic calcium overload, mediated via ORAI1, contributes to the pathogenesis of acute pancreatitis. ORAI1 inhibitors might be developed for the treatment of patients with pancreatitis.
Assuntos
Células Acinares/efeitos dos fármacos , Benzamidas/farmacologia , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Cálcio/metabolismo , Pancreatite/tratamento farmacológico , Pirazóis/farmacologia , Células Acinares/citologia , Doença Aguda , Animais , Ácidos e Sais Biliares/toxicidade , Cálcio/toxicidade , Células Cultivadas , Modelos Animais de Doenças , Células HEK293 , Humanos , Indóis/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Proteína ORAI1 , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Tapsigargina/toxicidade , Fatores de Tempo , Resultado do TratamentoRESUMO
Large oral doses of ACZ lower the intraocular pressure (IOP), but usually lead to a multitude of systemic side effects, including gastrointestinal upset. The present study was undertaken to evaluate the effect of ACZ on the histological structure of rat duodenal mucosa and to assess a possible protective role of the complex formation of ACZ with HP-ß-CD, either separately or in combination with a third compound, on the gut epithelial layer by histological and ultrastructural examinations of sections of rat duodenum exposed to ACZ or its formulations. In addition, the transport process of ACZ and its binary or ternary complexes across the duodenal mucosa by means of the single-pass intestinal perfusion (SPIP) method in rats was evaluated. Evidence was found that ACZ alters intestinal permeability and induces damage to the rat small intestine. In contrast, ACZ-induced intestinal injury may be abrogated by ACZ complexation. In addition, the complexation of ACZ with HP-ß-CD, alone or in combination with a third compound, facilitated significant levels of ACZ uptake across the rat duodenal segment. Ternary complexes of ACZ with HP-ß-CD in combination with TEA (triethanolamine) or calcium ions were found to provide an excellent approach that enabled an increased apparent permeability of ACZ across the duodenal epithelium, with a concomitant ability to preserve the integrity of the gut epithelium from ACZ-induced injury. These results could be useful for the design and development of novel ACZ formulations that can reduce GI toxicity, while still maintaining their essential therapeutic efficacies.
Assuntos
Acetazolamida , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Acetazolamida/administração & dosagem , Acetazolamida/química , Acetazolamida/farmacocinética , Acetazolamida/toxicidade , Animais , Cálcio/administração & dosagem , Cálcio/química , Cálcio/farmacocinética , Cálcio/toxicidade , Duodeno/efeitos dos fármacos , Duodeno/patologia , Duodeno/ultraestrutura , Etanolaminas/administração & dosagem , Etanolaminas/química , Etanolaminas/farmacocinética , Etanolaminas/toxicidade , Absorção Intestinal , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Ratos Wistar , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacocinética , beta-Ciclodextrinas/toxicidadeRESUMO
Because mitochondrial oxidative stress and impairment are important mediators of neuronal damage in neurodegenerative diseases and in brain ischemia/reperfusion, in the present study, we evaluated the antioxidant and mitoprotective effect of a new promising neuroprotective molecule, JM-20, in mitochondria and synaptosomes isolated from rat brains. JM-20 inhibited succinate-mediated H2O2 generation in both mitochondria and synaptosomes incubated in depolarized (high K(+)) medium at extremely low micromolar concentration and with identical IC50 values of 0.91 µM. JM-20 also repressed glucose-induced H2O2 generation stimulated by rotenone or by antimycin A in synaptosomes incubated in high sodium-polarized medium at extremely low IC50 values of 0.395 µM and 2.452 µM, respectively. JM-20 was unable to react directly with H2O2 or with superoxide anion radicals but displayed a cathodic reduction peak at -0.71V, which is close to that of oxygen (-0.8V), indicating high electron affinity. JM-20 also inhibited uncoupled respiration in mitochondria or synaptosomes and was a more effective inhibitor in the presence of the respiratory substrates glutamate/malate than in the presence of succinate. JM-20 also prevented Ca(2+)-induced mitochondrial permeability transition pore opening, membrane potential dissipation and cytochrome c release, which are key pathogenic events during stroke. This molecule also prevented Ca(2+) influx into synaptosomes and mitochondria; the former effect was a consequence of the latter because JM-20 inhibition followed the patterns of carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP), which is a classic mitochondrial uncoupler. Because the mitochondrion is considered an important source and target of neuronal cell death signaling after an ischemic insult, the antioxidant and protective effects of JM-20 against the deleterious effects of Ca(2+) observed at the mitochondrial level in this study may endow this molecule with the ability to succeed in mitochondrion-targeted strategies to combat ischemic brain damage.
Assuntos
Antioxidantes/farmacologia , Benzodiazepinas/farmacologia , Cálcio/toxicidade , Mitocôndrias/efeitos dos fármacos , Niacina/análogos & derivados , Prosencéfalo/ultraestrutura , Sinaptossomos/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Catalase/farmacologia , Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Niacina/farmacologia , Oligomicinas/farmacologia , Oxigênio/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismoRESUMO
This paper reports data on the relative ability of CaO, CaCl2, MgO, MgCl2, TiO2, and hectorite (SHCa-1) to induce oxidative stress (as determined by lipid peroxidation, LP) in biological matrices. The effectiveness of structural (oxide form) versus soluble Ca and Mg to induce LP is compared. An assessment on cytotoxicity as affected by soluble and structural Ca, Mg, TiO2 and SHCa-1 is also addressed. LP was screened and monitored using the Thiobarbituric Acid Reactive Substances (TBARS). The extent of TBARS production was found to vary with the type and initial concentration of the soluble or structural cation, Ca or Mg respectively. Obtained results showed higher magnitude values for the latter set of experiments. In the presence of TiO2 no significant TBARS production was detected pointing out a negligible effect of TiO2 on LP. At solid concentrations ca. 100 ppm, CaO appears to be more effective than SHCa-1 to induce LP. By contrast at ca. 25 ppm, MgO appears to be more effective than the clay mineral. The SHCa-1 LP-inducing activity has been proven to closely relate to structural Ca. The prevalence of mechanisms that may induce LP but not cytotoxicity (as determined by cell growth inhibition) was also addressed. Results on cell growth inhibition as affected by soluble and structural Ca, Mg, TiO2 and hectorite provide evidence to support that structural Ca or Mg brings about significantly higher variations than soluble Ca.
Assuntos
Cálcio/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Magnésio/toxicidade , Silicatos/toxicidade , Titânio/toxicidade , Animais , Cloreto de Cálcio/toxicidade , Cloreto de Magnésio/toxicidade , Óxido de Magnésio/toxicidade , Masculino , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Lotus species are forage legumes with potential as pastures in low-fertility and environmentally constrained soils, owing to their high persistence and yield under those conditions. The aim of this work was the characterization of phenetic and genetic diversity of salt-tolerant bacteria able to establish efficient symbiosis with Lotus spp. A total of 180 isolates able to nodulate Lotus corniculatus and Lotus tenuis from two locations in Granada, Spain, were characterized. Molecular identification of the isolates was performed by repetitive extragenic palindromic PCR (REP-PCR) and 16S rRNA, atpD, and recA gene sequence analyses, showing the presence of bacteria related to different species of the genus Mesorhizobium: Mesorhizobium tarimense/Mesorhizobium tianshanense, Mesorhizobium chacoense/Mesorhizobium albiziae, and the recently described species, Mesorhizobium alhagi. No Mesorhizobium loti-like bacteria were found, although most isolates carried nodC and nifH symbiotic genes closely related to those of M. loti, considered the type species of bacteria nodulating Lotus, and other Lotus rhizobia. A significant portion of the isolates showed both high salt tolerance and good symbiotic performance with L. corniculatus, and many behaved like salt-dependent bacteria, showing faster growth and better symbiotic performance when media were supplemented with Na or Ca salts.
Assuntos
Alphaproteobacteria/classificação , Alphaproteobacteria/isolamento & purificação , Lotus/microbiologia , Raízes de Plantas/microbiologia , Microbiologia do Solo , Alphaproteobacteria/efeitos dos fármacos , Alphaproteobacteria/genética , Proteínas de Bactérias/genética , Cálcio/toxicidade , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Dados de Sequência Molecular , N-Acetilglucosaminiltransferases/genética , Oxirredutases/genética , Filogenia , RNA Ribossômico 16S/genética , Recombinases Rec A/genética , Sais/toxicidade , Análise de Sequência de DNA , Sódio/toxicidade , EspanhaRESUMO
The lignan otobaphenol, (8R,8'R,7R)-4'-hydroxy-5'-methoxy-3,4-methylenedioxy-2',7,8,8'-neolignan, extracted from Virola Aff. Pavonis leaves, completely inhibits at a concentration of 2.5 micro M the Fe(3+)-ascorbate-induced lipoperoxidation of rat liver mitochondria that was determined by oxygen consumption and accumulation of thiobarbituric acid-reactive species. At 25 micro M, it delays the mitochondrial permeability transition induced by tert-butyl hydroperoxide or Ca(2+), substantially inhibits the state 3 respiration, does not affect the state 4 respiration and the ADP/O ratio (with succinate), diminishes the rate of Ca(2+) uptake by mitochondria, and delays the ruthenium red-insensitive uncoupler-induced release of the loaded Ca(2+). Dose-dependent delaying of the calcium-induced swelling of mitochondria in the presence of otobaphenol nonlinearly correlates with its 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity. At 75 micro M and higher, this lignan causes mitochondrial aggregation and is able to aggregate itself, without mitochondria. The formed aggregates of otobaphenol do not cause an aggregation of subsequently added mitochondria. Thus, otobaphenol seems to be a promising target to prevent the oxidative stress death of cells.
Assuntos
Antioxidantes/farmacologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Fenóis/farmacologia , Animais , Ácido Ascórbico/antagonistas & inibidores , Ácido Ascórbico/farmacologia , Compostos de Bifenilo , Hidroxitolueno Butilado/farmacologia , Cálcio/química , Cálcio/metabolismo , Cálcio/toxicidade , Permeabilidade da Membrana Celular/efeitos dos fármacos , Compostos Férricos/antagonistas & inibidores , Compostos Férricos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Membranas Intracelulares/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Dilatação Mitocondrial/efeitos dos fármacos , NADP/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Fenóis/química , Picratos/antagonistas & inibidores , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , terc-Butil Hidroperóxido/toxicidadeRESUMO
Previous experiments showed that isolated hearts from ethanol-exposed rats show a marked increase in sensitivity to anoxic myocardial damage, and we suggested that this may be due to excess calcium entry through L-type voltage-operated calcium channels (L-VOCCs). To challenge this hypothesis, we investigated the effect of ethanol treatment ex vivo on a damaging stimulus, the "calcium paradox," which is associated with removal of calcium from the perfusate. Adult male Sprague-Dawley rats were exposed to intoxicating concentrations of ethanol for 6-10 days by inhalation. Isolated hearts from these animals were perfused with Krebs-Henseleit buffer by using a modified Langendorff technique, and the calcium paradox induced by a 10-min period of perfusion with calcium-free buffer, followed by reperfusion with calcium-containing buffer. Compared with controls, hearts from ethanol-exposed rats were significantly protected against myocardial damage, as shown by a marked reduction in release of intracellular proteins (lactate dehydrogenase, creatine phosphokinase, and myoglobin) during the reperfusion phase. These indices of myocardial damage were modified by the presence of the dihydropyridine (DHP) calcium channel antagonist nitrendipine (10(-6) M) and the DHP L-VOCC activator Bay K 8644 (10(-7) M) in the perfusate during the calcium paradox. Paradoxically, both drugs appeared to increase the damaging effects of calcium-free perfusion, with this effect being generally greater in the preparations from ethanol-exposed rats. As a result, the difference between these hearts and those from control rats was reduced, although a significant degree of protection against the calcium paradox remained. The results support the hypothesis that long-term exposure to ethanol in vivo produces marked alterations in the toxic effects of changes in myocardial calcium concentration. The increased sensitivity to DHP drugs of isolated hearts from ethanol-treated rats is consistent with previous experiments showing increased DHP radioligand-binding sites in these tissues.
Assuntos
Alcoolismo/fisiopatologia , Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/toxicidade , Depressores do Sistema Nervoso Central/toxicidade , Di-Hidropiridinas/farmacologia , Etanol/toxicidade , Coração/efeitos dos fármacos , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Cálcio/metabolismo , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Masculino , Miocárdio/enzimologia , Nitrendipino/farmacologia , Perfusão , Ratos , Ratos Sprague-DawleyRESUMO
In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca2+]o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10(-9) to 10(-7) M, verapamil (10(-9) to 10(-7) M) and diltiazem (10(-9) to 10(-7) M) induced a concentration-dependent synergism of the log concentration-effect of garlic dialysate on left atria. Verapamil and diltiazem (10(-7)M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 x 10(-10) to 1.1 x 10(-6) M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca2+]o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Alho/metabolismo , Átrios do Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Plantas Medicinais , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/toxicidade , Animais , Cálcio/toxicidade , Agonistas dos Canais de Cálcio/toxicidade , Diálise , Diltiazem/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Sinergismo Farmacológico , Átrios do Coração/metabolismo , Masculino , Nifedipino/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Verapamil/farmacologiaRESUMO
Isolated rat liver mitochondria undergo extensive swelling and disruption of membrane potential when they accumulate Ca2+ in the presence of a prooxidant such as diamide or t-butylhydroperoxide. The phenothiazinic drug trifluoperazine, at concentrations (15-35 microM) which do not inhibit respiration or the influx of Ca2+ into mitochondria, significantly protected mitochondria against the deleterious effects of Ca2+ plus a prooxidant. In contrast, at concentrations higher than 100 microM the drug potentiated these deleterious effects of Ca2+ and prooxidants and had a damaging effect per se on the inner mitochondrial membrane. It is proposed that the protection conferred by the drug is mediated by changes in membrane protein structure that decrease the production of protein thiol cross-linkings which occur when mitochondria accumulate calcium under oxidant stress conditions.
Assuntos
Cálcio/toxicidade , Mitocôndrias Hepáticas/efeitos dos fármacos , Oxidantes/toxicidade , Trifluoperazina/farmacologia , Animais , Cálcio/antagonistas & inibidores , Cálcio/fisiologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/fisiologia , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/fisiologia , Cinética , Potenciais da Membrana/efeitos dos fármacos , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/fisiologia , Mitocôndrias Hepáticas/metabolismo , Dilatação Mitocondrial/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Wistar , Succinatos/farmacologia , Compostos de Sulfidrila/metabolismoRESUMO
La lititasis renal es un trastorno relativamente frecuente en la practica medica. No existe en la literatura colombiana una revision reciente y actualizada acerca de este tema por lo cual se escribio la presente. En una forma practica y simplificada, pero completa, se analizan los diferentes aspectos relacionados con la litiasis por calcio y brevemente, se mencionan otros tipos de calculos. Se hace enfasis en fisiopatologia, evaluacion del paciente, manejo de la litiasis (liquidos, dieta y drogas) y nuevos metodos de extraccion de calculo. No se incluye el manejo del colico renal
Nephrolithiasis is a relatively common disease in medical practice. There are no recent, updated reviews on this topic in Colombian literature and to fill this need the present one was written. The different aspects of calcium lithiasis are analyzed in a practical and simplified although comprehensive way, emphasizing pathophysiology, patient evaluation, management of lithiasis (fluids, diet and drug therapy) and new methods for stone removal. Other types of calculi are briefly discussed. Management of the renal colic is not included