RESUMO
In randomized groups of Wistar rats, the effect inhibitor of selective NASAID over the COX-1, COX-2 and COX-3 the synchronizes inhibition of COX-1 and COX-2, COX-1 and COX-3, COX-2 and COX-3, and COX-1, COX-2 and COX-3 were studied. The conclusions were that the selective inhibition of COX-1, COX-2 and COX-3 no given gastrointestinal damage; the synchronizes inhibition of COX-1 and COX-2 given preferential gastric damage; in contrast the inhibition of COX-2 and COX-3 given massive necrosis preferential in small intestine.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Trato Gastrointestinal/efeitos dos fármacos , Isoenzimas/antagonistas & inibidores , Animais , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/enzimologia , Trato Gastrointestinal/enzimologia , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases , RatosRESUMO
In randomized groups of Wistar rats, the effect inhibitor of selective NASAID over the COX-1, COX-2 and COX-3 the synchronizes inhibition of COX-1 and COX-2, COX-1 and COX-3, COX-2 and COX-3, and COX-1, COX-2 and COX-3 were studied. The conclusions were that the selective inhibition of COX-1, COX-2 and COX-3 no given gastrointestinal damage; the synchronizes inhibition of COX-1 and COX-2 given preferential gastric damage; in contrast the inhibition of COX-2 and COX-3 given massive necrosis preferential in small intestine.
RESUMO
In randomized groups of Wistar rats, the effect inhibitor of selective NASAID over the COX-1, COX-2 and COX-3 the synchronizes inhibition of COX-1 and COX-2, COX-1 and COX-3, COX-2 and COX-3, and COX-1, COX-2 and COX-3 were studied. The conclusions were that the selective inhibition of COX-1, COX-2 and COX-3 no given gastrointestinal damage; the synchronizes inhibition of COX-1 and COX-2 given preferential gastric damage; in contrast the inhibition of COX-2 and COX-3 given massive necrosis preferential in small intestine.(AU)
Assuntos
Animais , Feminino , Ratos , /efeitos adversos , Inibidores de Ciclo-Oxigenase , Trato Gastrointestinal/efeitos dos fármacos , Isoenzimas/antagonistas & inibidores , Prostaglandina-Endoperóxido Sintases , Trato Gastrointestinal/enzimologia , Trato Gastrointestinal/patologia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/enzimologiaRESUMO
In randomized groups of Wistar rats, the effect inhibitor of selective NASAID over the COX-1, COX-2 and COX-3 the synchronizes inhibition of COX-1 and COX-2, COX-1 and COX-3, COX-2 and COX-3, and COX-1, COX-2 and COX-3 were studied. The conclusions were that the selective inhibition of COX-1, COX-2 and COX-3 no given gastrointestinal damage; the synchronizes inhibition of COX-1 and COX-2 given preferential gastric damage; in contrast the inhibition of COX-2 and COX-3 given massive necrosis preferential in small intestine.
Assuntos
Animais , Feminino , Ratos , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase , Trato Gastrointestinal/efeitos dos fármacos , Isoenzimas/antagonistas & inibidores , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/enzimologia , Trato Gastrointestinal/enzimologia , Trato Gastrointestinal/patologia , Prostaglandina-Endoperóxido SintasesRESUMO
In 5 random groups of Wistar rats (n = 15 for each group), ulcerogenic doses of NSAIDs COX-1-COX-2 inhibitors such as indomethacin were compared with Celecoxib (COX-2 inhibitor); the production of antrum gastric ulcers and bowel and colon necrotic areas was studied. Celecoxib was given each 12 hs orally and subcutaneously during 5 days and gastrointestinal lesions were not found; in contrast, Celecoxib given after indomethacin aggravated antrum gastric ulcers (p < 0.001); intestinal massive necrosis and death were observed in all the rats. We conclude that Celecoxib does not induce gastrointestinal lesions in healthy mucosa; in contrast, Celecoxib amplifies the gastrointestinal lesions induced by indomethacin.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/toxicidade , Sistema Digestório/efeitos dos fármacos , Indometacina/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Sulfonamidas/toxicidade , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Celecoxib , Inibidores de Ciclo-Oxigenase/administração & dosagem , Feminino , Indometacina/administração & dosagem , Masculino , Necrose , Antro Pilórico/lesões , Pirazóis , Ratos , Ratos Wistar , Úlcera Gástrica/patologia , Sulfonamidas/administração & dosagemRESUMO
UNLABELLED: Five experimental models were carried out in different groups of Wistar rats (n = 15) in order to study selective (cyclo-oxygenase) COX-2 non-steroid antiinflammatory inhibitors, such as celecoxib and rofecoxib, as follows: 1) Dose-dependent oral celecoxib and rofecoxib for 5 days, and 24 hours after oral indomethacin. 2) Same as 1, but subcutaneously. 3) Gastric ulcer induced by means of glacial acetic acid. 4) Duodenal ulcer induced by means of cysteamine. 5) Stress due to being kept under restraint and immersion in water at 15 degrees C for 6 hours. Celecoxib and rofecoxib, either orally or subcutaneously, did not produce necrotic injuries in healthy gastrointestinal mucosa (0%), showing normal histology. On the other hand, the injuries previously induced by indomethacin worsened (90%, p < 0.001). Total necrosis of small intestine as well as increased ulcer and perforation of gastric and duodenal ulcers induced by acetic acid and cysteamine were observed. There was also worsening of gastric necrotic area with stress (60-90%, p < 0.05). Celecoxib and rofecoxib showed neutrophilia (5,000/mm3) similar to that presented by indomethacin, but there was no leukocyte infiltration in the gastric mucosa; thus we can consider it a COX-2 selective NSAID (non-steroidal anti-inflammatory drug). CONCLUSION: Dose-dependent administration of celecoxib and rofecoxib as COX-2 inhibitors and non-COX-1 inhibitors, respectively, did not produce toxic injuries on healthy gastrointestinal mucosa, thus providing a broad therapeutic spectre. On the other hand, when administered in presence of altered gastrointestinal mucosa, they worsened and complicated gastric ulcers, and also induced necrosis in the small intestine, thereby restricting their clinical use.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Lactonas/efeitos adversos , Sulfonamidas/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Celecoxib , Inibidores de Ciclo-Oxigenase/administração & dosagem , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Lactonas/administração & dosagem , Masculino , Úlcera Péptica Perfurada/induzido quimicamente , Pirazóis , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Sulfonamidas/administração & dosagem , SulfonasRESUMO
En diferentes grupos de ratas Wistar (n=15), se estudiaron AINEs inhibidores selectivos de la COX-2, como delecoxib y refecoxib, en cinco modelos experimentales: 1) Celecoxib y rofecoxib por vía oral y dosis dependiente durante 5 días y 24 hs. Después de indometacina oral. 2) Similar a 1, pero subcutáneo. 3) Ulcera gástrica inducida por ácido acético glacial. 4) Ulcera duodenal por cisteamina. 5) Estrés por inmovilización e inmersión en agua a 15 grados Celsius durante 6 horas. Celecoxib y rofecoxib por vía oral o SC en mucosa gastrointestinal sana no provaron lesiones necróticas en una superficie del 0 grados Celsius, presentanto histología normal; en cambio, agravaron y complicaron lesiones inducidas en forma previa por indometacina en más del 90 por ciento (p<0,001), con necrosis masiva del intestino delgado, así como ampliaron y causaron perforaciones en las úlceras gástricas y duodenales inducidas por ácido acético y cisteamina. Se produjo asimismo agravación de la zona necrótica gástrica por estrés en un 60-90 por ciento (p<0,05). Celecoxib y rofecoxib condujeron a una neutrofilia de 5000/mm3, similar a la inducida por la indometacina; en cambio, no produjeron infiltración leucocitaria en mucosa gástrica (MPO), siendo un marcador de AINE selectivo COX-2. Se concluyó que celecoxib y rofecoxib, administrados en dosis dependiente como inhibidores de COX-2 y no COX-1, no provocaron en mucosa gastrointestinal sana ninguna lesión por toxicidad, observándose un amplio margen terapéutico. En cambio, suministrados en mucosa gastrointestinal dañada agravaron y complicaron las lesiones ulcerosas gástricas y necróticas intestinales, limitando su uso en clínica.
Assuntos
Animais , Masculino , Feminino , Ratos , Inibidores de Ciclo-Oxigenase/toxicidade , Inibidores Enzimáticos/toxicidade , Indometacina/toxicidade , Lactonas/toxicidade , Úlcera Péptica Perfurada/induzido quimicamente , Prostaglandina-Endoperóxido Sintases , Úlcera Gástrica/induzido quimicamente , Estresse Fisiológico , Sulfonamidas/toxicidade , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Indometacina , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Lactonas/administração & dosagem , Infiltração de Neutrófilos , Ratos Wistar , Sulfonamidas/administração & dosagemRESUMO
En diferentes grupos de ratas Wistar (n=15), se estudiaron AINEs inhibidores selectivos de la COX-2, como delecoxib y refecoxib, en cinco modelos experimentales: 1) Celecoxib y rofecoxib por vía oral y dosis dependiente durante 5 días y 24 hs. Después de indometacina oral. 2) Similar a 1, pero subcutáneo. 3) Ulcera gástrica inducida por ácido acético glacial. 4) Ulcera duodenal por cisteamina. 5) Estrés por inmovilización e inmersión en agua a 15 grados Celsius durante 6 horas. Celecoxib y rofecoxib por vía oral o SC en mucosa gastrointestinal sana no provaron lesiones necróticas en una superficie del 0 grados Celsius, presentanto histología normal; en cambio, agravaron y complicaron lesiones inducidas en forma previa por indometacina en más del 90 por ciento (p<0,001), con necrosis masiva del intestino delgado, así como ampliaron y causaron perforaciones en las úlceras gástricas y duodenales inducidas por ácido acético y cisteamina. Se produjo asimismo agravación de la zona necrótica gástrica por estrés en un 60-90 por ciento (p<0,05). Celecoxib y rofecoxib condujeron a una neutrofilia de 5000/mm3, similar a la inducida por la indometacina; en cambio, no produjeron infiltración leucocitaria en mucosa gástrica (MPO), siendo un marcador de AINE selectivo COX-2. Se concluyó que celecoxib y rofecoxib, administrados en dosis dependiente como inhibidores de COX-2 y no COX-1, no provocaron en mucosa gastrointestinal sana ninguna lesión por toxicidad, observándose un amplio margen terapéutico. En cambio, suministrados en mucosa gastrointestinal dañada agravaron y complicaron las lesiones ulcerosas gástricas y necróticas intestinales, limitando su uso en clínica. (AU)
Assuntos
Animais , Masculino , Feminino , Ratos , Sulfonamidas/toxicidade , Prostaglandina-Endoperóxido Sintases , Inibidores de Ciclo-Oxigenase/toxicidade , Lactonas/toxicidade , Inibidores Enzimáticos/toxicidade , Úlcera Péptica Perfurada/induzido quimicamente , Úlcera Gástrica/induzido quimicamente , Estresse Fisiológico , Indometacina/toxicidade , Ratos Wistar , Modelos Animais de Doenças , Indometacina , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Infiltração de Neutrófilos , Sulfonamidas/administração & dosagem , Lactonas/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologiaRESUMO
Five experimental models were carried out in different groups of Wistar rats (n = 15) in order to study selective (cyclo-oxygenase) COX-2 non-steroid antiinflammatory inhibitors, such as celecoxib and rofecoxib, as follows: 1) Dose-dependent oral celecoxib and rofecoxib for 5 days, and 24 hours after oral indomethacin. 2) Same as 1, but subcutaneously. 3) Gastric ulcer induced by means of glacial acetic acid. 4) Duodenal ulcer induced by means of cysteamine. 5) Stress due to being kept under restraint and immersion in water at 15 degrees C for 6 hours. Celecoxib and rofecoxib, either orally or subcutaneously, did not produce necrotic injuries in healthy gastrointestinal mucosa (0
), showing normal histology. On the other hand, the injuries previously induced by indomethacin worsened (90
, p < 0.001). Total necrosis of small intestine as well as increased ulcer and perforation of gastric and duodenal ulcers induced by acetic acid and cysteamine were observed. There was also worsening of gastric necrotic area with stress (60-90
, p < 0.05). Celecoxib and rofecoxib showed neutrophilia (5,000/mm3) similar to that presented by indomethacin, but there was no leukocyte infiltration in the gastric mucosa; thus we can consider it a COX-2 selective NSAID (non-steroidal anti-inflammatory drug). CONCLUSION: Dose-dependent administration of celecoxib and rofecoxib as COX-2 inhibitors and non-COX-1 inhibitors, respectively, did not produce toxic injuries on healthy gastrointestinal mucosa, thus providing a broad therapeutic spectre. On the other hand, when administered in presence of altered gastrointestinal mucosa, they worsened and complicated gastric ulcers, and also induced necrosis in the small intestine, thereby restricting their clinical use.
RESUMO
In 5 random groups of Wistar rats (n = 15 for each group), ulcerogenic doses of NSAIDs COX-1-COX-2 inhibitors such as indomethacin were compared with Celecoxib (COX-2 inhibitor); the production of antrum gastric ulcers and bowel and colon necrotic areas was studied. Celecoxib was given each 12 hs orally and subcutaneously during 5 days and gastrointestinal lesions were not found; in contrast, Celecoxib given after indomethacin aggravated antrum gastric ulcers (p < 0.001); intestinal massive necrosis and death were observed in all the rats. We conclude that Celecoxib does not induce gastrointestinal lesions in healthy mucosa; in contrast, Celecoxib amplifies the gastrointestinal lesions induced by indomethacin.