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1.
J Gastroenterol Hepatol ; 22(11): 1872-6, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17914962

RESUMO

BACKGROUND AND AIM: Octreotide is considered to reduce exocrine pancreatic secretion in acute hemorrhagic necrotizing pancreatitis decreasing pancreatic autodigestion. The aim of this study was to determine whether octreotide also has antioxidative effects in acute pancreatitis. Additionally time and dose of application were of interest. METHOD: Ninety male Sprague-Dawley rats were randomized into six groups (n = 15). Group 1 underwent a laparotomy, and animals in groups 2-6 received intraductal glycodeoxycholic acid followed by intravenous cerulein. Groups 3 and 4 were injected with 0.5 mg octreotide, while groups 5 and 6 received continuous intravenous infusion of 0.05 mg octreotide/h for 10 h. Treatment was initiated 6 hours after induction of pancreatitis (IP) in groups 3 and 5, and 14 h after IP in groups 4 and 6. At 24 h after IP all animals were killed and each pancreas was analyzed histopathologically. In addition, levels of pancreatic lipid peroxidation protective enzymes glutathione-peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as lipid peroxidation via thiobarbituric acid reactive substances (TBARS) were determined. RESULTS: Early bolus application of octreotide reduced severity of histopathological changes in acute pancreatitis and decreased lipid peroxidation in pancreatic tissue samples; however, late bolus application and continuous intravenous infusion did not influence pancreatitis or lipid peroxidation. CONCLUSION: Octreotide seems to have a dose- and time-dependent effect on histopathology and lipid peroxidation in a model of pancreatitis in rats.


Assuntos
Antioxidantes/farmacologia , Hemorragia/prevenção & controle , Octreotida/farmacologia , Pâncreas/efeitos dos fármacos , Pancreatite Necrosante Aguda/prevenção & controle , Animais , Antioxidantes/administração & dosagem , Ceruletídeo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Ácido Glicodesoxicólico , Hemorragia/etiologia , Hemorragia/metabolismo , Hemorragia/patologia , Infusões Intravenosas , Injeções Intravenosas , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Octreotida/administração & dosagem , Pâncreas/enzimologia , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite Necrosante Aguda/induzido quimicamente , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/metabolismo , Pancreatite Necrosante Aguda/patologia , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
2.
Invest New Drugs ; 23(2): 157-64, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15744592

RESUMO

BACKGROUND: There is controversial discussion whether metastasis initiated by laparoscopy with carbon dioxide might be prevented by instillation of taurolidin or radical scavengers like the somatostatin analogue Octreotide. Therefore we evaluated the effects of laparoscopic lavage with taurolidin and Octreotide on liver metastasis after staging laparoscopy in ductal pancreatic cancer. METHODS: In 60 Syrian hamsters pancreatic adenocarcinoma was induced by weekly subcutanous injection of 10 mg N-nitrosobis-2-oxopropylamin/kg body weight for 10 weeks. In the 16th week laparoscopic staging biopsy by use of carbon dioxide was performed. Finally animals underwent abdominal irrigation with saline (gr.1, n = 20), taurolidin (0.5%) (gr.2, n = 20) or Octreotide (gr.3, n = 20). In week 25 animals were sacrificed, pancreas and liver were analysed. RESULTS: Size of pancreatic carcinomas was decreased in the taurolidin gr. compared to the other two groups. Furthermore the number of liver metastasis per animal was reduced after lavage with taurolidin (2 +/- 2) and Octreotide (2.5 +/- 2) compared to saline irrigation (4 +/- 4) (p < 0.05). Additionally the incidence of port site metastases was significantly reduced in the taurolidin group. Activity of antioxidative enzyme superoxide dismutase (SOD) was increased while concentration of products of lipidperoxidation was decreased in non-metastatic liver after taurolidin irrigation compared to saline or Octreotide irrigation. CONCLUSIONS: Taurolidin irrigation during laparoscopy might be a new concept to reduce the number of liver metastasis and port site metastases in pancreatic cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Laparoscopia/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Hepáticas/prevenção & controle , Octreotida/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Taurina/análogos & derivados , Taurina/uso terapêutico , Tiadiazinas/uso terapêutico , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/patologia , Animais , Carcinoma Ductal Pancreático/induzido quimicamente , Carcinoma Ductal Pancreático/patologia , Cricetinae , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Mesocricetus , Metástase Neoplásica/prevenção & controle , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/patologia
3.
Pancreatology ; 2(3): 211-6, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12138726

RESUMO

BACKGROUND: The therapeutic effects of octreotide in acute hemorrhagic necrotizing pancreatitis (ANP) have always been considered to be due to the inhibition of the exocrine pancreatic secretion in order to reduce pancreatic autodigestion. In this experimental study we analyzed whether octreotide has also antioxidative effects on acute pancreatitis. METHODS: 40 male Wistar rats were randomized into four groups (n = 10). Group 1 underwent a laparotomy. Groups 2-4 received an injection of natrium taurocholate into the pancreatic duct to induce acute pancreatitis. One hour later group 2 was injected 1 ml NaCl solution intraperitoneally, while groups 3 and 4 received 0.1 or 0.2 mg octreotide, respectively. The severity of ANP was examined histologically. The lipid peroxide level as well as the activity of glutathione peroxidase and superoxide dismutase were measured in plasma and pancreatic tissue samples. RESULTS: High-dose octreotide decreased the lipid peroxide level in plasma (2.1 +/- 0.53 vs. 4.69 +/- 1.35 nmol/l; p < 0.05) and pancreatic tissue samples 4.67 +/- 1.37 vs. 13.20 +/- 2.93 nmol/ml; p < 0.05) compared to the pancreatitis control group. Low-dose octreotide, however, did not reduce lipid peroxidation. CONCLUSION: Octreotide seems to have a dose-dependent antioxidative effect in natrium taurocholate-induced pancreatitis in rats.


Assuntos
Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/sangue , Octreotida/farmacologia , Pâncreas/metabolismo , Pancreatite Necrosante Aguda/metabolismo , Animais , Antioxidantes/administração & dosagem , Relação Dose-Resposta a Droga , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Masculino , Octreotida/administração & dosagem , Concentração Osmolar , Pancreatite Necrosante Aguda/induzido quimicamente , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Ácido Taurocólico , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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