RESUMO
Presentation of a study conducted on 20 male Wistar rats treated for 3 months with Leuprolide (LHRH agonist). Analysis of pathophysiological testicular changes resulting from the treatment and extent of recovery at 3 months of therapy discontinuation, relating those changes to testosterone plasma levels in peripheral blood. Serum testosterone fell to 1.17 +/- 0.30 ng/ml in the treated group, shifting to figures overlapping with normal values within 3 months of discontinuing treatment. Such decreased testosterone levels translate into significant testicular histological damage. Three months after interruption of treatment there is nearly complete recovery of such damage, with just around 10% tubules without spermatozoa, with unchanged germinal line. We conclude that the marked suppression in testosterone levels caused by LHRH agonists translates into a significant degeneration of the seminiferous tubule, which appears to be reversible 3 months after treatment discontinuation.
Assuntos
Leuprolida/farmacologia , Testículo/efeitos dos fármacos , Testículo/patologia , Animais , Leuprolida/administração & dosagem , Masculino , Ratos , Ratos Wistar , Testosterona/sangue , Fatores de TempoAssuntos
Fígado , Soluções para Preservação de Órgãos , Preservação de Órgãos/métodos , Adenosina/farmacologia , Alopurinol/farmacologia , Análise de Variância , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Glutationa/farmacologia , Insulina/farmacologia , L-Lactato Desidrogenase/análise , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/análise , Rafinose/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo , Ureia/análiseAssuntos
Adenosina/farmacologia , Alopurinol/farmacologia , Isquemia/fisiopatologia , Fígado/irrigação sanguínea , Reperfusão , Alanina Transaminase/análise , Animais , Aspartato Aminotransferases/análise , L-Lactato Desidrogenase/análise , Fígado/efeitos dos fármacos , Fígado/patologia , Testes de Função Hepática , Masculino , Ratos , Ratos Wistar , Fatores de TempoAssuntos
Isquemia , Veias Jugulares/cirurgia , Circulação Hepática , Fígado/irrigação sanguínea , Veias Mesentéricas/cirurgia , Reperfusão/métodos , Alanina Transaminase/análise , Animais , Aspartato Aminotransferases/análise , Capilares/fisiologia , Capilares/fisiopatologia , L-Lactato Desidrogenase/análise , Fígado/patologia , Masculino , Necrose , Sistema Porta , Ratos , Ratos Wistar , Fluxo Sanguíneo RegionalAssuntos
Isquemia , Fígado/irrigação sanguínea , Reperfusão , Alanina Transaminase/análise , Análise de Variância , Animais , Aspartato Aminotransferases/análise , Veias Jugulares/cirurgia , L-Lactato Desidrogenase/análise , Fígado/fisiologia , Testes de Função Hepática , Masculino , Malondialdeído/análise , Veias Mesentéricas/cirurgia , Peroxidase/análise , Ratos , Ratos Wistar , Circulação Esplâncnica , Fatores de TempoAssuntos
Intestino Delgado , Intestino Delgado/transplante , Neutrófilos/fisiologia , Soluções para Preservação de Órgãos , Preservação de Órgãos , Adenina , Adenosina , Alopurinol , Animais , Dextranos , Combinação de Medicamentos , Glutationa , Sobrevivência de Enxerto , Soluções Hipertônicas , Insulina , Intestino Delgado/patologia , Masculino , Rafinose , Ratos , Ratos Sprague-Dawley , Transplante Heterotópico/patologiaRESUMO
A study was performed in 20 male Wistar rats weighing 250-300 gm; 10 comprised the control group and the other 10 were treated with 5 mg/day of cyproterone acetate which was given with the meal for 2 months. The rat testicular microcirculation was studied by laser Doppler flowmetry. Similarly, the testicular interstitial fluid volume and plasma testosterone in peripheral blood were determined. Within each of the two groups, 5 were studied without any pharmacologic stimulation and 5 at 4 hours following the administration of 100 IU subcutaneous HCG. The rats treated with cyproterone acetate had very low levels of serum testosterone (1.254 +/- 0.667) versus the control group (3.686 +/- 0.705), the difference being statistically significant (p < 0.05). Following administration of HCG, the microcirculation changes and the interstitial fluid were the same as those of the control group despite the blockade of the androgenic receptors by cyproterone acetate. The increase in testosterone levels therefore does not appear to mediate the testicular microcirculation changes produced by HCG.
Assuntos
Gonadotropina Coriônica/farmacologia , Testículo/irrigação sanguínea , Testosterona/fisiologia , Antagonistas de Receptores de Andrógenos , Animais , Velocidade do Fluxo Sanguíneo , Barreira Hematotesticular/efeitos dos fármacos , Líquidos Corporais , Permeabilidade Capilar , Gonadotropina Coriônica/administração & dosagem , Acetato de Ciproterona/farmacologia , Masculino , Microcirculação/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Periodicidade , Ratos , Ratos Wistar , Testículo/efeitos dos fármacos , Testosterona/sangue , Testosterona/farmacologiaRESUMO
To examine the role of neutrophils, their presence and the degree of infiltration, as important determinants of ischemia and reperfusion injury of the liver, male Sprague-Dawley rats were subjected to 60 and 90 min of total-liver ischemia. The presence of neutrophils, assessed by the measurement of liver tissue myeloperoxidase (MPO), and the degree of neutrophil liver infiltration, determined by the naphthol AS-D chloroacetate esterase technique, correlated well with animal survival and response to FK506 and cyclosporine administration. Lipid peroxidation, measured by the malondialdehyde (MDA) test in liver tissue, was another factor closely linked with liver function and survival. Pretreatment with FK506 (0.3 mg/kg) and CsA (5 mg/kg) was given at 4 hr and 1 hr before ischemia and at the time of reperfusion. Control ischemic animals showed increased neutrophil liver infiltration, high MPO and MDA liver levels, and diminished overall survival. FK506 and CsA-treated animals had better survival and diminished neutrophil liver infiltration, as well as MPO and MDA levels. The mechanism by which FK506 and CsA protected the animals from severe liver ischemic injury is unknown. Our data indicated that the presence and the degree of infiltration of neutrophils were important components of liver ischemia/reperfusion injury in the rat. So it is possible that one of the fundamental effects of the FK506 and CsA might be through the inhibition of the presence and infiltration of neutrophils in liver tissue.
Assuntos
Ciclosporina/farmacologia , Isquemia/patologia , Fígado/irrigação sanguínea , Neutrófilos/fisiologia , Traumatismo por Reperfusão/patologia , Tacrolimo/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , L-Lactato Desidrogenase/sangue , Fígado/ultraestrutura , Masculino , Malondialdeído/metabolismo , Microscopia Eletrônica , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Análise de SobrevidaRESUMO
CaCl2 (0.1-25 mM, in K(+)-depolarized tissues), KCl (10-112 mM) and acetylcholine (1 nM-1 mM) produced concentration-dependent contractions of rat isolated fundus. Nifedipine (0.01-500 mcM), diltiazem (0.01-100 mcM) and flunarizine (10-500 mcM) each produced a concentration-related inhibition of the log concentration-effect curve for CaCl2. The rank order of potencies of these antagonists, measured as the IC50 against Ca2+ (25 mM)-induced contraction of depolarized fundus, was nifedipine (1.9 mcM) = diltiazem (2.5 mcM) >> flunarizine (660 mcM). Diltiazem depressed KCl-induced contraction with an effectiveness and potency similar to that displayed against CaCl2 but nifedipine and flunarizine were less effective against contractions to KCl compared to CaCl2. Flunarizine (500 mc), but not the other antagonists tested, depressed Ca2+ (20 mc)-evoked contraction of skinned rat fundus preparations. It is concluded that distinct differences exist between the Ca2+ channel antagonists examined. The action of nifedipine and diltiazem is restricted to the plasmalemma, whereas flunarizine also acts on the intracellular contractile apparatus.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Fundo Gástrico/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Cálcio/antagonistas & inibidores , Cálcio/farmacologia , Cloreto de Cálcio/farmacologia , Interações Medicamentosas , Feminino , Masculino , Membranas/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Ratos , Ratos WistarRESUMO
Study carried out in 50 male Wistar rats distributed into 5 groups: baseline and at 2, 4, 8 and 24 hours after subcutaneous injection of Human Chorionic Gonadotropin, 100 IU. It was observed that testicular microcirculatory flow shows a rhythmical fluctuating pattern (5-10 fluctuations per minute), which becomes continuous at 4 hours but recovers at 24 hours. At the same time, there is an increased volume of testicular interstitial fluid that peaks at 8 hours, and returns to baseline levels at 24 hours. Serum testosterone values increase with HCG injection, reaching a peak at 4 hours (25.9 mg/ml), to return to nearly baseline levels at 24 hours (5.04 mg/ml). Disappearance of the rhythmical microcirculatory pattern, and the increase of interstitial fluid volume do not appear to be mediated by testosterone, since the raise in hormone levels, occurred after HCG administration, preceded the observed microcirculatory changes.
Assuntos
Fluxometria por Laser-Doppler , Testículo/irrigação sanguínea , Animais , Gonadotropina Coriônica/administração & dosagem , Masculino , Microcirculação , Periodicidade , Ratos , Testosterona/sangueRESUMO
CaCl2 (0.01-50 mM, in K(+)-depolarized tissues), KCl (0.1-100 mM) and acetylcholine (1 nM-10 mM) produced concentration-dependent contractions of guinea-pig isolated gall bladder. Nifedipine (1-100 microM), verapamil (1-100 microM), diltiazem (1-100 microM), cinnarizine (1-100 microM), and flunarizine (1-100 microM) each produced a concentration-related inhibition of the log concentration-effect curve for CaCl2. The rank order of potencies of these antagonists, measured as the IC50 against Ca2+ (50 mM)-induced contraction of depolarized gall bladder, was diltiazem (0.25 microM) > or = verapamil (0.8 microM) approximately nifedipine (1.2 microM) >> cinnarizine (25 microM) approximately flunarizine (80 microM). Verapamil and diltiazem depressed KCl-induced contraction with an effectiveness and potency similar to those displayed against CaCl2 but nifedipine, cinnarizine and flunarizine were less effective against contractions in response to KCl compared to CaCl2. Verapamil and diltiazem, but not the other Ca2+ channel antagonists tested, had a specific inhibitory effect on the contractions due to KCl when compared to acetylcholine-induced contractions. Cinnarizine (10-100 microM) and flunarizine (10-100 microM), but not the other antagonists tested, depressed Ca2+ (20 microM)-evoked contraction of skinned guinea-pig gall bladder preparations. It is concluded that distinct differences exist between the Ca2+ channel antagonists examined. The action of nifedipine, verapamil and diltiazem is restricted to the plasmalemma whereas cinnarizine and flunarizine also act on the intracellular contractile apparatus.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Vesícula Biliar/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Acetilcolina/antagonistas & inibidores , Animais , Cloreto de Cálcio/antagonistas & inibidores , Membrana Celular/fisiologia , Feminino , Cobaias , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Cloreto de Potássio/antagonistas & inibidoresRESUMO
In determining whether rice-bran oil (RBO) has antisecretory activity, we induced stress ulcers in 20 Wistar rats (10 controls; 10 animals given 0.2 ml/day RBO orally for 4 days prior to ulcer induction). In turn, we analyzed gastric juice for histamine, pepsin, H+ concentration ([H+]) and output volume. A second, complementary study was made of basal and stimulated gastric secretion through continuous "in vivo" recording of output. Secretion was stimulated with increasing doses of histamine, betanechol and pentagastrin. Ninety-four rats were used (47 controls and 47 rats given 0.2 ml/day RBO orally for 4 days prior to gastric output evaluation). The results were evaluated by the Student t-test. Ulcer index in the RBO-treated rats was significantly lower than among the controls (p less than 0.01), as also reflected by a significantly greater decrease in [H+] among the RBO-treated rats (p less than 0.05). However, no significant differences were observed for the remaining parameters. Continuous recording of basal gastric output showed a significant decrease in [H+] among the RBO-treated rats (p less than 0.01). Following histamine stimulation, [H+] was likewise significantly lower among the RBO-treated rats than in the controls. However, no significant differences were observed following stimulation with either betanechol or pentagastrin. RBO contains a high percentage of unsaturated fats; the latter act as precursors in the synthesis of arachidonic acid, which in turn is the essential precursor of prostaglandins--established inhibitors of gastric secretion. RBO also contains antioxidants such as alpha-tocopherol, which may likewise stimulate the synthesis of prostaglandins. RBO likely acts by increasing prostaglandin output, thus interfering with gastric HCl production.