RESUMO
The aim of this study was to investigate the protective mechanisms of delayed-phase morphine preconditioning on myocardial ischemia-reperfusion injury. Thirty healthy male New Zealand white rabbits were randomly divided into three groups: a sham operation group (C), ischemia-reperfusion group (I/R), and delayed-phase morphine preconditioning group (M) (N = 10/group). Rabbits in the C group received thoracotomy for 160 min. Rabbits in the I/R group received left artery blockage for 40 min and reperfusion for 120 min. Rabbits in the M group received 1.0 mg/kg intravenous morphine 24 h prior to the identical treatment as the rabbits in the I/R group. In each group, the interleukin (IL)-10 and tumor necrosis factor (TNF)-α levels were detected at five time points: 20 min before the left coronary artery blockage (T1), 20 and 40 min after the left coronary artery blockage (T2 and T3, respectively), and 1 and 2 h after the myocardial reperfusion (T4 and T5, respectively). After reperfusion, the infarction size was measured with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Compared with the C group, serum IL-10 and TNF-α concentrations increased in the I/R and M groups; the difference was significant (P < 0.05). When compared with the I/R group, the IL-10 concentrations in the M group were significantly increased (P < 0.05), but the infarction size and TNF-α concentrations were significantly decreased (P < 0.05). These results suggested that delayed-phase morphine preconditioning might achieve myocardial protection through the regulation and balance of inflammatory cytokines.
Assuntos
Precondicionamento Isquêmico/métodos , Morfina/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Interleucina-10/sangue , Masculino , Coelhos , Distribuição Aleatória , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/sangueRESUMO
This study aimed to investigate the protective effects of delayed morphine preconditioning on myocardial ischemia-reperfusion injury. We randomly divided 30 rabbits into three groups with 10 rab-bits in each group as follows: sham operation group (C group), isch-emia-reperfusion group (I/R group), and morphine pretreatment group (M group). Rabbits in C Group received left coronary without blocking for 160 min. The left descending artery of rabbits in the I/R group was blocked for 40 min and reperfused for 120 min. Rabbits in the M group received intravenous administration of 1.0 mg/kg morphine; after 24 h, rabbits in this group received the same treatment as that administered to the I/R group. We determined tumor necrosis factor alpha (TNF-α) levels in blood samples from the internal carotid artery of rabbits in each group 20 min before occlusion of the left descending coronary artery, 20 and 40 min after occlusion of the left descending coronary artery, and 1 and 2 h after myocardial reperfusion. After 120 min of reperfusion, immunoblotting was used to measure the activity levels of myocardial p38 mitogen-activated protein kinase (MAPK); in addition, the infarct size was measured. Compared to the I/R group, the M group showed a significant decrease in TNF-α levels, p38 MAPK activity, and the myocardial infarct size (I/R group 37.8% ± 1.7% vs 21.5% ± 2.4%; P < 0.05). Thus, morphine preconditioning in the delayed phase may exert protective effects on myocardial I/R injury by inhibiting myocar-dial p38 MAPK activity and decreasing TNF-α production.
Assuntos
Estenose Coronária/tratamento farmacológico , Precondicionamento Isquêmico Miocárdico/métodos , Morfina/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Entorpecentes/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Estenose Coronária/genética , Estenose Coronária/metabolismo , Estenose Coronária/patologia , Modelos Animais de Doenças , Expressão Gênica , Injeções Intravenosas , Masculino , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Coelhos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
This study aimed to investigate the protective effects and the mechanisms underlying these effects of isoflurane preconditioning in the delayed phase of myocardial ischemia-reperfusion injury. We randomly divided 30 healthy male New Zealand white rabbits into three groups with 10 rabbits in each group as follows: sham operation group (C group), ischemia-reperfusion group (I/R group), and 2.0% isoflurane preconditioning group (S group). Rabbits in the C group received thoracotomy for 160 min. Rabbits in the I/R group underwent left coronary artery occlusion for 40 min and reperfusion for 120 min. Rabbits in the S group received inhalation of 2.0% isoflurane and 100% oxygen for 2 h; after 24 h, rabbits in this group received the same treatment as that administered to rabbits in the I/R group. We examined the tumor necrosis factor alpha (TNF-α) levels in each group 20 min before occlusion of the left coronary, 20 and 40 min after occlusion of the left coronary artery, and 1 and 2 h after myocardial reperfusion. After reperfusion, immunoblotting was used to measure the myocardial caspase-3 expression levels, and the infarct size was measured using Evans blue and tetrazolium chloride staining. The levels of TNF-α and caspase-3 were lower in the S group than in the I/R group, and the myocardial infarct size decreased in the S group. Thus, isoflurane preconditioning in the delayed phase exerted protective effects by decreasing the myocardial caspase-3 expression and TNF-α production in a rabbit model of ischemia-reperfusion injury.
Assuntos
Caspase 3/metabolismo , Precondicionamento Isquêmico/métodos , Isoflurano/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo , Animais , Caspase 3/biossíntese , Masculino , Modelos Animais , Miocárdio/metabolismo , CoelhosRESUMO
We examined the protective effects of Ginkgo biloba extract (EGb761) postconditioning on myocardial ischemia reperfusion injury in rabbits. Four groups of 8 white rabbits were allocated to: pseudo surgery group: the left coronary was lined without blocking for 160 min after thoracotomy; ischemia and reperfusion group (IR): the left anterior descending coronary artery was blocked for 40 min and reperfused for 120 min; ischemic postconditioning group: the left anterior descending artery was ligated for 40 min, reopened for 30 s and ligated for 30 s, repeated three times, and then reperfused for 120 min; EGb761 postconditioning group (E): 100 mg/kg EGb761 was injected into a vein while the left coronary artery was opened for 1 min. The reperfusion took 120 min. Internal carotid arterial blood in each group was collected for cTnI measurement at five times: 20 min before occlusion of the left coronary artery, 20 min after left coronary artery occlusion, 40 min after left coronary artery occlusion, 1 h after myocardial reperfusion, and 2 h after myocardial reperfusion. Superoxide dismutase (SOD), malondialdehyde (MDA) in the centrifuged blood and myocardial infarction area were measured at the end of reperfusion. We found that the serum cTnI concentrations in the E group during reperfusion decreased significantly compared with those in the IR group. The infarction area was significantly lower in the E group than that in the IR group. The SOD activity in the E group was increased compared with that in the IR group; the MDA content decreased significantly in the E group compared with that in the IR group. We conclude that G. biloba extract postconditioning had myocardial protection effects by reducing the generation of oxygen-free radicals and increasing the antioxidant capacity of the myocardial cells.
Assuntos
Ginkgo biloba/química , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Modelos Animais de Doenças , Humanos , Pós-Condicionamento Isquêmico/métodos , Masculino , Malondialdeído/sangue , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Extratos Vegetais/química , Coelhos , Superóxido Dismutase/sangueRESUMO
Cycloserine (Seromycin)was found to be moderately, effective in the suppression of intraperitoneally infected mouse leprosy. The smallest dosages used, 0.2 per cent in the food, showed minimal effects. Higher doses showed greater activity, of about the same order as that exhibited by streptomycin, but much less than that of isoniazid. Cycloserine has been reported to be beneficial in human tuberculosis but to have no effect in experimental tuberculosis of mice and guinea-pigs. The discovery of its suppressive action in murine leprosy suggests the desirability of the extension of screening tests to other mycobacterial infections in the search for more active antituberculosis agents.
Assuntos
Ratos , Hanseníase , Hanseníase/diagnóstico , Hanseníase/prevenção & controle , Hanseníase/tratamento farmacológicoRESUMO
The activity of isoniazid, isonicotinylhydrazone of 2-carboxymethoxy-3-methoxybenzaldehyde (compound 373), and isonicotinylhydrazone of 2-carboxymethoxybenzaldehyde (compound 377) was compared, in equimolar doses, in mice infected intraperitoneally with M. leprae murium. All three compounds were found to be highly effective in the suppression of the murine lleprosy infection in the three-months experiment. They were most effective when treatment was started immediately after inoculation and continued for three months, and proportionally less effective when treatment was delayed for one month and then continued for two months. The degree of activity of the three compounds was more or less equal. When mice were treated for three months and allowed to live, all three compounds suppressed the infection for a period; then the disease remanifested itself, killing the animals. The suppressive activity of isoniazid and Compound 373 was similar, while that of Compound 377 was the highest. When mice were treated with either isoniazid or Compound 373 continuosly for 15 months from thhe time of inoculation, the survival time was definitely longer than when they were treated for only three monmths. Eventually, however, the infection led to death regardless of the duration of treatment. Isoniazid revealed activity similar to that of Compound 373. On the other hand, the continuous administration of Compound 377 for 15 months suppressed the infection in the majority of the mice. This appears to be the first drug to hold this infection in check for as long as 15 months.
Assuntos
Hanseníase , Hanseníase/diagnóstico , Hanseníase/prevenção & controle , Hanseníase/tratamento farmacológicoRESUMO
The effects of various combinations of small doses of 4,4'-diaminodiphenyl sulfone (DDS), streptomycin and isoniazid (isonicotinic acid hydrazide) have been studied in intraperitoneally-infected mouse leprosy. The suppressive effects of various combinations of these drugs were definitely superior to those obtained with the individual drugs alone. The order of activity of the drugs and combinations used, based on the decreasing total indices of chemotherapeutic effectiveness, may be expressed as follows: (1) streptomycin, isoniazid, and DDS combined; (2) isoniazid and DDS; (3) streptomycin and isoniazid; (4) streptomycin and DDS; (5) streptomycin alone; (6) isoniazid; (7) DDS.
Assuntos
Esquema de Medicação , Hanseníase , Hanseníase/terapiaRESUMO
Studies have been made of the therapeutic effects on murine leprosy of several drugs and antibiotics, employing the intraperitoneally-infected mopuse. The following results were obtained: Amithiozone (TB1/698) seemed to cause some stimulation of the infection. PAS (p-aminosalicylic acid), B283 (a phenazine pigment), chlortetracycline (Aureomycin), oxytetracycline (Terramycin), Chloramphenicol (Chloromycetin), penicillin, erythromycin (Ilotycin), and three derivatives of diphenylthiourea, i. e., SU-1795, Su-1906 and SU-2358, revealed no significant activity.
Assuntos
Esquema de Medicação , Hanseníase , Hanseníase/classificação , Hanseníase/diagnóstico , Hanseníase/terapiaRESUMO
A brief review of the pharmacological actions of nicotinamide and allied compounds in relation to the mycobacterial infections has been presented. The activity of nicotinamide and pyrazinamide (Aldinamide) in mouse leprosy has been studied, employing the intraperitoneal route for infection. Comparative studies of the activity of these compounds with that of three known effective drugs- isoniazid, streptomycin and DDS - were made in animals treated immediately after inoculation or after delays of one or two months. The duration of the experiments was three months. Both nicotinamide and pyrazinamide were found to be highly effective in the suppression of the leprous infection. Nicotinamide was found to have a degree of activity similar to that of pyrazinamide and of isoniazid, and superior to that of streptomycin; DDS was the least active. All these five compounds were most effective when the treatment was delayed for one or two months. Only nicotinamide, pyrazinamide and isoniazid possessed any significant activity when the treatment was delayed for two months and then carried out for only one months.