RESUMO
The effect of the acute-phase response on the clearance rate of plasma kallikrein by the exsanguinated liver was studied in three groups of rats: a control group and two other groups that received either turpentine or an endogenous pyrogen preparation. The plasma kallikrein clearance rates were significantly higher in both inflamed groups.
Assuntos
Reação de Fase Aguda/metabolismo , Calicreínas/metabolismo , Fígado/metabolismo , Reação de Fase Aguda/induzido quimicamente , Animais , Camundongos , Pirogênios , Coelhos , Ratos , Ratos Wistar , TerebintinaRESUMO
The participation of corticosteroids and alpha 2-macroglobulin (alpha 2-M) in counter-irritation (CI) induced by carrageenin was studied. We observed that CI could be produced when the second stimulus was done after 24 h, at which time glucocorticoids had already returned to their basal levels but alpha 2-M levels were maximum. When the level of alpha 2-M decreased (48 h) the counter-irritatory effect was not observed. As the synthesis of this protein is corticosteroid-dependent, we did not observe CI in adrenalectomized rats. However, when adrenalectomy was done 20 h after the first stimulus, allowing the synthesis of large amounts of alpha 2-M, the carrageenin stimulus again produced CI. Furthermore, adrenalectomized rats treated with aprotinin, a kallikrein inhibitor, after the first carrageenin stimulus, showed a reduction of the response to the second carrageenin stimulus. These observations demonstrated that corticosterone was not directly responsible for this inhibitory effect. Nevertheless, the anti-inflammatory factors involved in CI were, in fact, corticosteroid-dependent and alpha 2-M was probably one of the main factors.
Assuntos
Irritantes/farmacologia , alfa-Macroglobulinas/fisiologia , Adrenalectomia , Animais , Aprotinina/farmacologia , Carragenina , Corticosterona/sangue , Edema/induzido quimicamente , Edema/fisiopatologia , Masculino , Ratos , Ratos EndogâmicosRESUMO
Rat plasma kallikrein (RPK) is a serine protease that circulates as an inactive precursor, prokallikrein, and once activated is efficiently cleared by the liver by a carbohydrate-dependent, Ca2+ - independent mecanism. Seven hepatic lectin systems have been described for mammals but not all of these animal lectins are expressed in the avian liver. Using a liver perfusion system we compared the plasmakallikrein clearance of rats (N=10) and pigeons (N+4). Our results show that the lectin responsible for the hepatic clearance of plasma kallikrein is also present in pigeon liver and that this organ clears the enzyme with an efficiency (11.4 ñ 1.3 pmol/g,20 min) similar to that of the rat liver (10.0 ñ 0.7 pmolg, 20 min)_
Assuntos
Ratos , Animais , Fígado/metabolismo , Calicreínas/sangue , Columbidae , Calicreínas/metabolismo , Taxa de Depuração Metabólica , Receptores Mitogênicos/farmacologiaRESUMO
In view of the known interactions between pineal and adrenal glands and the importance of glucocorticoids on the acute phase of inflammatory process, we investigated the effect of the pineal gland on the paw edema response induced by carrageenin in female Wistar rats, weighing 170-220 g, measured by the pletysmographic method. Adrenalectomy increased the rate of the inflammatory response (149.02 +/- 2.93%, N = 7 vs 113.48 +/- 2.99%, N = 7) whereas pinealectomy and sham-pinealectomy under white light had an inhibitory effect (81.73 +/- 2.16%, N = 15 and 80.21 +/- 1.85%, N = 14 vs 113.48 +/- 2.99%, N = 7). Sham-pinealectomy under red light did not modify the rate of the inflammatory response. These results indicate that the pineal gland can be affected by light during sham-pinealectomy. In view of the unaltered adrenal gland weight and corticosterone levels among the different groups, we propose an antagonism between melatonin (pineal hormone) and glucocorticoids at the peripheral level. The predominant effect of glucocorticoids over melatonin may explain the inhibition of the inflammatory response caused by pinealectomy.
Assuntos
Reação de Fase Aguda/etiologia , Adrenalectomia , Luz , Glândula Pineal/cirurgia , Animais , Carragenina , Corticosterona/sangue , Feminino , Melatonina/biossíntese , Melatonina/farmacologia , Ratos , Ratos EndogâmicosRESUMO
Rat plasma kallikrein (RPK) is a serine protease that circulates as an inactive precursor, prokallikrein, and once activated is efficiently cleared by the liver by a carbohydrate-dependent, Ca(2+)-independent mechanism. Seven hepatic lectin systems have been described for mammals but not all of these animal lectins are expressed in the avian liver. Using a liver perfusion system we compared the plasma kallikrein clearance of rats (N = 10) and pigeons (N = 4). Our results show that the lectin responsible for the hepatic clearance of plasma kallikrein is also present in pigeon liver and that this organ clears the enzyme with an efficiency (11.4 +/- 1.3 pmol/g, 20 min) similar to that of the rat liver (10.0 +/- 0.7 pmol/g, 20 min).
Assuntos
Calicreínas/sangue , Fígado/metabolismo , Animais , Columbidae , Calicreínas/metabolismo , Taxa de Depuração Metabólica , Ratos , Receptores Mitogênicos , Especificidade da EspécieRESUMO
In view nof the known interactions between pineal and adrenal glands and the importance of glucocorticoids on the acute phase of the inflammatory process, we investigated the effect of the pineal gland on the paw edema response induced by carrageenin in female Wistar rats, weighing 170-220 g, measured by the pletysmographic method. Adrenalectomy increased the rate of the inflammatory response (149.02 ñ 2.93%, N=7 vs 113.48 ñ 2.99%, N=7) whereas pinealectomy and sham-pinealectomy under white light had an inhibitory effect (81.73 ñ 2.16%, N=15 and 80.21 ñ 1.85%, N=14 vs 113.48 ñ 2.99%, N=7). Sham-pinealectomy under red light did not modify the rate of the inflammatory response. These results indicate that the pineal gland can be affected by light during sham-pinealectomy. In view of the unaltered adrenal gland weight and corticosterone levels among the different groups, we propose an antagonism between melatonin (pineal hormone) and glucocorticoids at the peripheral level. The predominant effect of glucocorticoids over melatonin may explain the inhibition of the inflammatory response caused by pinealectomy
Assuntos
Ratos , Animais , Feminino , Reação de Fase Aguda/etiologia , Adrenalectomia , Carragenina/farmacologia , Luz , Glândula Pineal/cirurgia , Corticosterona/sangue , Melatonina/biossíntese , Melatonina/farmacologia , Ratos EndogâmicosRESUMO
During the acute phase of the inflammatory process there is a characteristic increase in some plasma proteins called collectively acute phase reactants (APR) as well as in the levels of corticosteroids. A bacterial endotoxin (LPS) that induces a strong acute phase response, indicated by high levels of fibrinogen and haptoglobin, did not show this effect when administered to rats treated previously with metopyrone, a specific inhibitor of corticosteroid hormone synthesis. These results suggest that adequate levels of these hormones are important for the production of acute phase reactants.
Assuntos
Endotoxinas/farmacologia , Fibrinogênio/biossíntese , Haptoglobinas/biossíntese , Metirapona/farmacologia , Proteínas de Fase Aguda/biossíntese , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Corticosterona/sangue , Dexametasona/farmacologia , Feminino , Masculino , RatosRESUMO
The effect of sex steroids on the plasma levels of alpha 2-macroglobulin (alpha 2-M) was investigated to explain the sexual dimorphism observed in response to the injury caused by ip administration of 5 micrograms endotoxin. Mean serum alpha 2-M concentrations were lower in female (46.82 +/- 8.10 arbitrary units) than in male injured rats (82.94 +/- 9.22 arbitrary units). A reduction of plasma alpha 2-M levels was observed after orchidectomy, and the administration of 1 mg testosterone to the same animals increased the response. The same response pattern was observed in ovariectomized rats under the same treatment. The response of androgenized rats (78.93 +/- 12.81 arbitrary units) to injury was similar to the male response. These results suggest the importance of testosterone as the major determinant of this sex-dependent response.
Assuntos
Reação de Fase Aguda/etiologia , Hormônios Esteroides Gonadais/farmacologia , Caracteres Sexuais , alfa-Macroglobulinas/metabolismo , Animais , Endotoxinas/farmacologia , Feminino , Masculino , Orquiectomia , Ovariectomia , Ratos , Ratos EndogâmicosRESUMO
Acute phase response of plasma alpha 1-major acute phase (alpha 1-MAP) was studied in normal and adrenalectomized rats. alpha 1-MAP basal levels were higher in female than in male rats. This protein, measured by radial immunodiffusion, increased significantly both in male and female rats 24 and 48 h after a turpentine stimulus, proving to be a positive acute phase protein for both sexes. In adrenalectomized male rats the increase of plasma alpha 1-MAP concentration was not different from that observed in sham-operated rats, suggesting that the acute phase response of this protein is not corticoid dependent.
Assuntos
Proteínas de Fase Aguda/análise , Adrenalectomia , Corticosterona/sangue , Terebintina/farmacologia , Animais , Feminino , Masculino , Ratos , Ratos EndogâmicosRESUMO
The effect of sex steroids on the plasma levels of alfa2-macroglobulin (alfa-2M) was investigated to explain the sexual dimorphism observed in response to the injuries caused by ip administration of 5 microng endotoxin. Mean serum alfa2-M concentrations were lower in female (46.82 ñ8.10 arbitrary units) than in male injured rats (82.94 ñ 9.22 arbitrary units). a reduction of plasma alfa2-M levels was observed after orchidectomy, and the administration of 1 mg testosterone to the same animals increased the response. The same response pattern wa observed in ovariectomized rats under the same treatment. The response of androgenized rats (78.93 ñ 12.81 arbitrary units) to injury was similar to the male response. These results suggest the importance of testosterone as the major determinant of this sex-dependent response
Assuntos
Ratos , Animais , Masculino , Feminino , Reação de Fase Aguda/etiologia , alfa-Macroglobulinas/metabolismo , Caracteres Sexuais , Hormônios Esteroides Gonadais/farmacologia , Endotoxinas/farmacologia , Orquiectomia , Ovariectomia , Ratos WistarRESUMO
Acute phase response of plasma alfa-1-major acute phase (alfa1-MAP) was studied in normal and adrenalectomized rats. Alfa1-MAP basal levels were higher in female than in male rats. This proteins, measured by radial immunodiffusion, increased significantly both in male and female rats 24 and 48 h after a turpentine stimulus, proving to be a positive acute phase protein for both sexes. In adrenalectomized male rats the increase of plasma alfa-1MAP concentration was not different from that observed in sham-operated rats, suggesting that the acute phase response of this protein is not corticoid dependent
Assuntos
Ratos , Animais , Masculino , Feminino , Adrenalectomia , alfa 1-Antitripsina/análise , Corticosterona/sangue , Terebintina/farmacologia , Ratos WistarRESUMO
Rats treated with monosodium glutamate (MSG) during the neonatal period show hypothalamic lesions and multiple neuroendocrine alterations manifested as a remarkable increase in levels of circulating corticosterone and obesity. Paw edema induced by local injection of carrageenin was significantly reduced in MSG-treated rats compared to normal rats. In contrast, both adrenalectomized rats and adrenalectomized, MSG-treated rats showed an increased response to carrageenin relative to controls. These results suggest that glucocorticoids are important modulators of inflammation in this phase of the process.
Assuntos
Carragenina/farmacologia , Edema/induzido quimicamente , Glutamatos/farmacologia , Glutamato de Sódio/farmacologia , Adrenalectomia , Animais , Edema/prevenção & controle , Feminino , Masculino , Ratos , Ratos EndogâmicosRESUMO
Rats treated with monosodium glutamate (MSG) during the neonatal period show hypothalamic lesions and multiple neuroendocrine alterations manifested as a remarkable increase in levels of circulating corticosterone and obesity. Paw edema induced by local injection of carrageenin was significantly reduced in MSG-treated rats compared to normal rats. In contrast, both adrenalectomized rats and adrenalectomized, MSG-treated rats showed an increased response to carrageenin relative to controls. These results suggest that glucocorticoids are important modulators of inflammation in this phase of the process
Assuntos
Ratos , Animais , Masculino , Feminino , Carragenina/farmacologia , Edema/induzido quimicamente , Glutamato de Sódio/administração & dosagem , AdrenalectomiaAssuntos
Ratos , Animais , Masculino , Corticosteroides/farmacologia , Fibrinogênio/metabolismo , Haptoglobinas/metabolismo , Leucotrieno B4/farmacologia , Antagonistas de Prostaglandina/farmacologia , Pirogênios/farmacologia , Adrenalectomia , Anti-Inflamatórios/farmacologia , Ibuprofeno/farmacologia , Pirazóis/farmacologiaRESUMO
Injections of endogenous pyrogen (EP) in normal rats significantly increased plasma concentration of haptoglobin and fibrinogen while in adrenalectomized animals the same treatment was ineffective. Nevertheless when cortisone was injected simultaneously with EP into adrenalectomized rats the responses of fibrinogen and haptoglobin were restored. These results suggest that biosynthesis of fibrinogen and haptoglobin is corticosteroid-dependent. Inhibition of the cyclo-oxygenase pathway with ibuprofen or the lipoxygenase pathway with BW755C had no effect on the increase of plasma fibrinogen or haptoglobin levels stimulated by either EP or endotoxin. These data indicate that neither prostaglandins nor leukotrienes are involved in the production of these acute phase reactants induced by either stimulus.