RESUMEN
BACKGROUND: Ursolic acid (UA) is found in many plants, and has been reported to have anti-protease, antioxidant, anti-inflammatory, antimicrobial, nephroprotective, hepatoprotective, and cardioprotective effects. OBJECTIVE: The purpose of this study was to investigate the effects of ursolic acid in cerulein-induced acute pancreatitis (AP). MATERIALS AND METHODS: Thirty-two Wistar albino rats were randomly assigned to 4 equal groups: Sham, acute pancreatitis, treatment, and ursolic acid group. RESULTS: Serum amylase levels in the AP and treatment groups were significantly higher than in the others (p < 0.05). In addition, serum IL-1ß, IL-6, and TNF-α levels were significantly higher in the AP group in comparison with the treatment group. Although pancreatic tissue total oxidant activity in the AP and treatment groups was similar, pancreatic tissue total antioxidant capacity was significantly higher in the treatment group than in the AP group. CONCLUSIONS: Damage to the pancreas and remote organs in AP was observed to be reduced by UA. In addition, oxidative stress was observed to be decreased by the effect of UA.
ANTECEDENTES: El ácido ursólico se encuentra en numerosas plantas y se ha informado que tiene efectos antiproteasas, antioxidantes, antiinflamatorios, antimicrobianos, nefroprotectores, hepatoprotectores y cardioprotectores. OBJETIVO: Este estudio tuvo como objetivo investigar los efectos del ácido ursólico en la pancreatitis aguda inducida por ceruleína. MATERIAL Y MÉTODOS: Treinta y dos ratas albinas Wistar fueron asignadas aleatoriamente a cuatro grupos iguales: grupo simulado, grupo de pancreatitis aguda, grupo de tratamiento y grupo de ácido ursólico. RESULTADOS: Los niveles de amilasa sérica en los grupos de pancreatitis aguda y de tratamiento fueron significativamente más altos que en los otros grupos (p < 0.05). Además, los niveles séricos de IL-1ß, IL-6 y TNF-α fueron significativamente más altos en el grupo de pancreatitis aguda en comparación con el grupo de tratamiento. Aunque la actividad oxidante total del tejido pancreático en ambos grupos fue similar, la capacidad antioxidante total del tejido pancreático en el grupo de tratamiento fue significativamente mayor. CONCLUSIÓN: Se observó que el ácido ursólico reduce el daño al páncreas y órganos remotos en la pancreatitis aguda, al igual que el estrés oxidativo.
Asunto(s)
Pancreatitis , Triterpenos , Ratas , Animales , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Ceruletida , Ratas Wistar , Enfermedad Aguda , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Triterpenos/farmacología , Triterpenos/uso terapéutico , Ácido UrsólicoRESUMEN
Agents that modulate the activity of high-voltage gated calcium channels (HVCCs) exhibit experimentally and clinically significant effect by relieving visceral pain. Among these agents, the toxins Phα1ß and ω-conotoxin MVIIA effectively reduce chronic pain in rodent models. The molecular mechanisms underlying the chronic pain associated with acute pancreatitis (AP) are poorly understood. Hypercalcemia is a risk factor; the role of cytosolic calcium is considered to be a modulator of pancreatitis. Blockade of Ca2+ signals may be useful as a prophylactic treatment of pancreatitis. We explored the pathophysiological roles of three peptide toxins: Phα1ß and its recombinant form CTK 01512-2-blockers of TRPA1 receptor and HVCCs and ω-conotoxin MVIIA, a specific blocker of N-type calcium channels in cerulein-induced AP. Cerulein injection elicits AP in rats, evidenced by an increase in hyperalgesic pain, inflammatory infiltration, amylase and lipase secretion, and reactive oxygen species, TNF-α, and p65 NF-κB levels. These effects of cerulein-induced AP were abolished by Phα1ß and its recombinant form CTK 01512-2, whereas ω-conotoxin MVIIA had no effect on the induced increase in pancreatic enzyme secretion. Our results demonstrate that Phα1ß and CTK 01512-2 toxins-antagonists of HVCCs and TRPA1 receptor presented an effective response profile, in the control of nociception and inflammatory process in the AP model in rats, without causing changes in spontaneous locomotion of the rats.
Asunto(s)
Dolor Abdominal/prevención & control , Analgésicos/farmacología , Antiinflamatorios/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/efectos de los fármacos , Hiperalgesia/prevención & control , Umbral del Dolor/efectos de los fármacos , Pancreatitis/prevención & control , Dolor Abdominal/etiología , Dolor Abdominal/metabolismo , Dolor Abdominal/fisiopatología , Animales , Conducta Animal/efectos de los fármacos , Canales de Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Ceruletida , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Mediadores de Inflamación/metabolismo , Masculino , Neuropéptidos/farmacología , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , Pancreatitis/fisiopatología , Ratas Wistar , Venenos de Araña/farmacología , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/fisiopatología , omega-Conotoxinas/farmacologíaRESUMEN
Acute pancreatitis is one of the first pathological processes where autophagy has been described in a human tissue. Autophagy, autodigestion, and cell death are early cellular events in acute pancreatitis. Recent advances in understanding autophagy highlight its importance in pathological conditions. However, methods for monitoring autophagic activity during complex diseases, involving highly differentiated secretory cells, are complicated, and the results are sometimes misinterpreted. Here, we describe methods used to identify autophagic structures and to measure autophagic flux in cultured cell models and animal models of pancreatitis. We also briefly describe the pancreas specific autophagy mouse model that was useful to understand the actual role of autophagy in pancreatitis and to identify a novel selective autophagy pathway named zymophagy. Lastly, we describe the immunomagnetic isolation of autophagosomes and the detection of autophagy in pancreatic tissue samples derived from humans.
Asunto(s)
Autofagosomas/patología , Autofagia , Precursores Enzimáticos/metabolismo , Páncreas/patología , Pancreatitis/patología , Células Acinares , Animales , Autofagosomas/ultraestructura , Técnicas de Cultivo de Célula/instrumentación , Técnicas de Cultivo de Célula/métodos , Línea Celular , Ceruletida/toxicidad , Modelos Animales de Enfermedad , Humanos , Lisosomas/metabolismo , Masculino , Ratones , Microscopía Electrónica/instrumentación , Microscopía Electrónica/métodos , Microscopía Fluorescente/instrumentación , Microscopía Fluorescente/métodos , Páncreas/citología , Pancreatectomía , Pancreatitis/inducido químicamente , Pancreatitis/cirugía , Ratas , Vesículas Secretoras/patologíaRESUMEN
Acute pancreatitis is a multifactorial disease associated with profound changes of the pancreas induced by release of digestive enzymes that lead to increase in proinflammatory cytokine production, excessive tissue necrosis, edema, and bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c-Met have been observed in different chronic and acute pancreatic diseases including experimental models of acute pancreatitis. In the present study, we investigated the protective effects induced by the recombinant human HGF in a mouse model of cerulein-induced acute pancreatitis. Pancreatitis was induced by 8 hourly administrations of supramaximal cerulein injections (50 µg/kg, ip). HGF treatment (20 µg/kg, iv), significantly attenuated lipase content and amylase activity in serum as well as the degree inflammation and edema overall leading to less severe histologic changes such as necrosis, induced by cerulein. Protective effects of HGF were associated with activation of pro-survival pathways such as Akt, Erk1/2, and Nrf2 and increase in executor survival-related proteins and decrease in pro-apoptotic proteins. In addition, ROS content and lipid peroxidation were diminished, and glutathione synthesis increased in pancreas. Systemic protection was observed by lung histology. In conclusion, our data indicate that HGF exerts an Nrf2 and glutathione-mediated protective effect on acute pancreatitis reflected by a reduction in inflammation, edema, and oxidative stress.
Asunto(s)
Factor de Crecimiento de Hepatocito/uso terapéutico , Pancreatitis/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Ceruletida , Modelos Animales de Enfermedad , Glutatión/biosíntesis , Factor de Crecimiento de Hepatocito/sangre , Factor de Crecimiento de Hepatocito/farmacología , Humanos , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Pancreatitis/patología , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-met/metabolismo , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacos , Análisis de SupervivenciaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the protective and therapeutic effects of quercetin on pancreatic injury in cerulein-induced acute pancreatitis. METHOD: Thirty-two rats were randomly divided into four groups, eight per group: (CT): untreated controls, (CER) treated with cerulein, 50 µg/kg body weight; (Q+CER) pre-treatment with quercetin, 100 mg/kg body weight, followed by cerulein, 50 µg/kg; (CER+Q) post-treatment, cerulein followed by quercetin, same doses. Cerulein was divided into four doses, given at 1-hour intervals by intraperitoneal injection. Quercetin was given either 1-hour before (in pre-treatment group) or 1-hour after (in post-treatment group) cerulein. Pancreatic malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), reduced and oxidized glutathione (GSH and GSSG, respectively) were measured. Histology of the pancreas was studied. RESULTS: (1) MDA, carbonyl, MPO, TNF-a and IL-6 levels were significantly higher in CER vs CT rats. (2) MDA, carbonyl, MPO and TNF-α decreased significantly in pre-treated rats vs. CER. (3) MDA, MPO, TNF-α, IL-6 were significantly lower in post-treated rats vs. CER. (4) The reduced vs. oxidized glutathione ratio (GSH/GSSG) of was significantly lower CER vs. CT rats. (5) Pre- and post-treatment with quercetin significantly increased this ratio. (6) Pancreatic histology showed that quercetin had no significant effect on the histological image of the pâncreas CONCLUSION: These results suggest that quercetin can attenuate the severity of cerulein-induced acute pancreatitis by acting as an antioxidant and anti-inflammatory agent and combating oxidative stress. Further studies are needed to clearly explain its utility on acute pancreatitis.
OBJETIVO: O objetivo deste estudo foi avaliar os efeitos protetores e terapêuticos da quercetina na lesão pancreática da pancreatite aguda induzida por ceruleína. MÉTODO: Trinta e dois ratos foram divididos aleatoriamente em quatro grupos, oito por grupo: (CT): controles não tratados (CER) tratados com ceruleína, 50 µg/kg de peso corporal; (Q+CER) pré-tratamento com quercetina, 100 mg / kg de peso corporal, seguido de ceruleína, 50 µg/kg; (CER+Q) pós-tratamento, ceruleína seguida de quercetina, mesmas doses. A ceruleína foi dividida em quatro doses, administradas a intervalos de 1 hora por injeção intraperitoneal. A quercetina foi administrada 1 hora antes (no grupo de pré-tratamento) ou 1 hora após (no pós-tratamento) a administração de ceruleína. Foram medidos o malondialdeído pancreático (MDA), carbonilo, mieloperoxidase (MPO), fator de necrose tumoral alfa (TNF-a), interleucina-6 (IL-6), glutationa reduzida e oxidada (GSH e GSSG, respetivamente). Foi estudada a histologia do pâncreas. RESULTADOS: Os níveis de MDA, carbonila, MPO, TNF-a e IL-6 foram significativamente maiores nos ratos CER vs. CT. MDA, carbonila, MPO e TNF-α diminuíram significativamente em ratos pré-tratados versus CER. MDA, MPO, TNF-α, IL-6 também foram significativamente menores em ratos pós-tratados versus CER. A proporção reduzida de glutationa oxidada (GSH/GSSG) foi significativamente menor ratos CER vs. CT; pré e pós-tratamento com quercetina aumentaram significativamente esta proporção. A histologia pancreática mostrou que a quercetina não teve efeito morfológico significativo. CONCLUSÃO: Estes resultados sugerem que a quercetina pode atenuar a gravidade da pancreatite aguda induzida por ceruleína, atuando como agente antioxidante e anti-inflamatório e combater o estresse oxidativo. Mais estudos são necessários para explicar claramente suas utilidades na pancreatite aguda.
Asunto(s)
Animales , Ratas , Pancreatitis/inducido químicamente , Quercetina/análisis , Ceruletida/efectos de los fármacos , Estrés Oxidativo , Distribución AleatoriaRESUMEN
BACKGROUND: The mechanisms underlying breathing exercises have not been fully elucidated. OBJECTIVES: To evaluate the impact of four on breathing exercises (diaphragmatic breathing, inspiratory sighs, sustained maximal inspiration and intercostal exercise) the on breathing pattern and thoracoabdominal motion in healthy subjects. METHOD: Fifteen subjects of both sexes, aged 23±1.5 years old and with normal pulmonary function tests, participated in the study. The subjects were evaluated using the optoelectronic plethysmography system in a supine position with a trunk inclination of 45° during quiet breathing and the breathing exercises. The order of the breathing exercises was randomized. Statistical analysis was performed by the Friedman test and an ANOVA for repeated measures with one factor (breathing exercises), followed by preplanned contrasts and Bonferroni correction. A p<0.005 value was considered significant. RESULTS: All breathing exercises significantly increased the tidal volume of the chest wall (Vcw) and reduced the respiratory rate (RR) in comparison to quiet breathing. The diaphragmatic breathing exercise was responsible for the lowest Vcw, the lowest contribution of the rib cage, and the highest contribution of the abdomen. The sustained maximal inspiration exercise promoted greater reduction in RR compared to the diaphragmatic and intercostal exercises. Inspiratory sighs and intercostal exercises were responsible for the highest values of minute ventilation. Thoracoabdominal asynchrony variables increased significantly during diaphragmatic breathing. CONCLUSIONS: The results showed that the breathing exercises investigated in this study produced modifications in the breathing pattern (e.g., increase in tidal volume and decrease in RR) as well as in thoracoabdominal motion (e.g., increase in abdominal contribution during diaphragmatic breathing), among others. .
CONTEXTUALIZAÇÃO: Os mecanismos envolvidos na execução dos exercícios respiratórios não foram completamente elucidados. OBJETIVOS: Avaliar o impacto de quatro exercícios respiratórios(diafragmático, suspiros inspiratórios, inspiração máxima sustentada e intercostal) sobre o padrão respiratório e o movimento toracoabdominal em indivíduos saudáveis. MÉTODO: Participaram do estudo15 indivíduos de ambos os sexos (23±1,5 anos com prova de função pulmonar normal). Os indivíduos foram avaliados por meio da pletismografia optoeletrônica na posição supina com inclinação de tronco de 45° durante a respiração tranquila e durante a realização dos exercícios respiratórios. A ordem dos exercícios foi randomizada. Os dados foram analisados pelo teste de Friedman e ANOVA para medidas repetidas com um fator (exercícios respiratórios) seguidos de contrastes pré-planejados e correção de Bonferroni, sendo p<0,005 considerado significativo. RESULTADOS: Todos os exercícios respiratórios promoveram aumento significativo do volume corrente da parede torácica (VCpt) e redução da frequência respiratória (f) quando comparados à respiração tranquila. O exercício diafragmático foi responsável pelo menor VCpt, menor contribuição da caixa torácica e maior contribuição do abdômen. A inspiração máxima sustentada promoveu redução significativamente maior da f comparada aos exercícios diafragmático e intercostal. Os exercícios suspiros inspiratórios e intercostal foram responsáveis pelos maiores valores de ventilação minuto. Os índices de assincronia toracoabdominal aumentaram significativamente ...
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ceruletida/uso terapéutico , Colelitiasis/terapia , Glicéridos/uso terapéutico , Solventes/uso terapéutico , Caprilatos , Colangiografía , Colelitiasis , Evaluación de MedicamentosRESUMEN
AIMS: Acute pancreatitis (AP) is an inflammatory condition wherein pro-inflammatory mediators, oxidative stress, and NF-κB signaling play a key role. Currently, no specific therapy exists and treatment is mainly supportive and targeted to prevent local pancreatic injury and systemic inflammatory complications. This study was aimed to examine whether 1,8-cineole, a plant monoterpene with antioxidant and anti-inflammatory properties could ameliorate cerulein-induced acute pancreatitis. MAIN METHODS: AP was induced in Swiss mice by six one hourly injections of cerulein (50 µg/kg, i.p.). 1,8-cineole (100, 200 and 400mg/kg, p.o.) was administered 1h prior to first cerulein injection, keeping vehicle and thalidomide treated groups as controls. Blood samples were taken 6-h later to determine serum levels of amylase and lipase, and cytokines. The pancreas was removed for morphological examination, myeloperoxidase (MPO) and malondialdehyde (MDA) assays, reduced glutathione (GSH) levels, and for nuclear factor (NF)-κB immunostaining. KEY FINDINGS: 1,8-cineole effectively reduced the cerulein-induced histological damage, pancreatic edema and NF-κB expression, levels of MPO activity and MDA, and replenished the GSH depletion. Cerulein increased serum levels of amylase and lipase, and pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were also decreased by 1,8-cineole pretreatment, similar to thalidomide, a TNF-α inhibitor. The anti-inflammatory IL-10 cytokine level was, however, enhanced by 1,8-cineole. SIGNIFICANCE: These findings indicate that 1,8-cineole can attenuate cerulein-induced AP via an anti-inflammatory mechanism and by combating oxidative stress. Further studies are needed to clearly elucidate its benefits in patients on acute pancreatitis.
Asunto(s)
Ceruletida/toxicidad , Ciclohexanoles/uso terapéutico , Citocinas/metabolismo , Monoterpenos/uso terapéutico , FN-kappa B/metabolismo , Estrés Oxidativo/fisiología , Pancreatitis/metabolismo , Pancreatitis/prevención & control , Animales , Ciclohexanoles/farmacología , Citocinas/fisiología , Eucaliptol , Masculino , Ratones , Monoterpenos/farmacología , FN-kappa B/fisiología , Estrés Oxidativo/efectos de los fármacos , Pancreatitis/inducido químicamenteRESUMEN
OBJECTIVE: To evaluate the anti-inflammatory effect of α,ß-amyrin, a pentacyclic triterpenoid from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was induced in Swiss mice by five intraperitoneal injections of cerulein (50 µg/kg), at 1 h intervals. Mice received α,ß-amyrin (10, 30 and 100 mg/kg), thalidomide (200 mg/kg), or vehicle (3% Tween 80) orally 1 h before and 12 h after the cerulein challenge. The severity of pancreatitis was evaluated 24 h after cerulein by assessing serum pro-inflammatory cytokines and amylase activity, pancreatic myeloperoxidase (MPO), and thiobarbituric acid-reactive substances (TBARS), as well as by histology. RESULTS: α,ß-Amyrin and thalidomide significantly attenuated the cerulein-induced increase in tumor necrosis factor (TNF)-α, interleukin-6, lipase, amylase, MPO, and TBARS. Moreover, α,ß-amyrin greatly suppressed the pancreatic edema, inflammatory cell infiltration, acinar cell necrosis, and expressions of TNFα and inducible nitric oxide synthase. CONCLUSIONS: α,ß-Amyrin ameliorates cerulein-induced acute pancreatitis by acting as an anti-inflammatory and antioxidant agent.
Asunto(s)
Antiinflamatorios/uso terapéutico , Burseraceae/química , Ceruletida/efectos adversos , Ácido Oleanólico/análogos & derivados , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Amilasas/sangre , Animales , Antiinflamatorios/química , Modelos Animales de Enfermedad , Inmunosupresores/uso terapéutico , Interleucina-6/sangre , Masculino , Ratones , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ácido Oleanólico/química , Ácido Oleanólico/uso terapéutico , Pancreatitis/patología , Peroxidasa/metabolismo , Distribución Aleatoria , Talidomida/uso terapéutico , Factor de Necrosis Tumoral alfa/sangreRESUMEN
AIM: To investigate chronic stress as a susceptibility factor for developing pancreatitis, as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer. METHODS: Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation. Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 µg/kg per hour) cerulein stimulation on chronically stressed rats. RESULTS: In vitro exposure of pancreatic acini to TNF-α disorganized the actin cytoskeleton. This was further increased by TNF-α/CCK treatment, which additionally reduced amylase secretion, and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner. TNF-α/CCK also enhanced caspases' activity and lactate dehydrogenase release, induced ATP loss, and augmented the ADP/ATP ratio. In vivo, rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels. Serum, pancreatic, and lung inflammatory parameters, as well as caspases'activity in pancreatic and lung tissue, were substantially enhanced in stressed/cerulein-treated rats, which also experienced tissues' ATP loss and greater ADP/ATP ratios. Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema, hemorrhage and leukocyte infiltrate, and pancreatic necrosis. Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-α-antibody, which diminished all inflammatory parameters, histopathological scores, and apoptotic/necrotic markers in stressed/cerulein-treated rats. CONCLUSION: In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation.
Asunto(s)
Páncreas Exocrino/inmunología , Pancreatitis/psicología , Estrés Psicológico/complicaciones , Factor de Necrosis Tumoral alfa/metabolismo , Actinas/metabolismo , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Amilasas/metabolismo , Animales , Anticuerpos/farmacología , Señalización del Calcio , Caspasas/metabolismo , Ceruletida , Colecistoquinina/metabolismo , Enfermedad Crónica , Citoesqueleto/metabolismo , Modelos Animales de Enfermedad , Activación Enzimática , Lesión Pulmonar/etiología , Lesión Pulmonar/inmunología , Lesión Pulmonar/psicología , Masculino , FN-kappa B/metabolismo , Necrosis , Páncreas Exocrino/efectos de los fármacos , Páncreas Exocrino/metabolismo , Páncreas Exocrino/patología , Pancreatitis/inducido químicamente , Pancreatitis/inmunología , Pancreatitis/metabolismo , Pancreatitis/patología , Pancreatitis/prevención & control , Proteína Quinasa C-delta/metabolismo , Proteína Quinasa C-epsilon/metabolismo , Transporte de Proteínas , Ratas , Ratas Wistar , Restricción Física , Índice de Severidad de la Enfermedad , Técnicas de Cultivo de Tejidos , Tripsina/metabolismo , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Many plant-derived flavonoids including quercetin exhibit antioxidant and antiinflammatory properties. Proinflammatory cytokines and oxidative stress play an important role in acute pancreatitis. This study aimed to evaluate the effect of quercetin on cerulein-induced acute pancreatitis in mice. Animal groups were pretreated with quercetin (25, 50, 100 mg/kg, per os (p.o.)), thalidomide (200 mg/kg, p.o.) or vehicle (2% dimethyl sulfoxide (DMSO)) 1 h before hourly (x5) intraperitoneal injections of cerulein. A saline (0.9%, NaCl)-treated control group was included for comparison. Cerulein significantly enhanced the serum levels of amylase and lipase, and pancreatic myeloperoxidase activities, malondialdehyde and the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6, as well as the pancreatic wet weight/body weight ratio. Cerulein significantly reduced the serum levels of IL-10. Histological assessment of the pancreas showed tissue edema, neutrophil infiltration, acinar vacuolization, and cell necrosis and a marked increase in the immunoreactivity staining for TNF-alpha. Pretreatment with quercetin or thalidomide significantly attenuated the severity of cerulein-induced acute pancreatitis as evidenced by effective reductions in the pancreatic wet weight/body weight ratio, biochemical indices, proinflammatory cytokines, myeloperoxidase activity, malondialdehyde formation, and an increase in antiinflammatory cytokine IL-10. Quercetin treatment also markedly suppressed the histological changes such as pancreatic edema, inflammatory cell infiltration, acinar cell necrosis, and the expression of TNF-alpha. Taken together, these results indicate that quercetin ameliorates the severity of cerulein-induced acute pancreatitis by acting as an antiinflammatory and antioxidant agent.
Asunto(s)
Ceruletida/toxicidad , Flavonoides/uso terapéutico , Pancreatitis/inducido químicamente , Pancreatitis/prevención & control , Quercetina/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Pancreatitis/patologíaRESUMEN
The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 microg/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 +/- 2.29, 20.89 +/- 10.13, 11.52 +/- 4.60, 18.69 +/- 8.56, and 8.58 +/- 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 +/- 0.83, 1.09 +/- 0.35, 2.05 +/- 0.91, 1.70 +/- 0.60, and 2.85 +/- 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 +/- 0.25, 0.33 +/- 0.09, 0.37 +/- 0.04, 0.34 +/- 0.07 and 0.42 +/- 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tissue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage.
Asunto(s)
Peroxidación de Lípido/efectos de los fármacos , Hepatopatías/etiología , Pancreatitis/complicaciones , Especies Reactivas de Oxígeno/metabolismo , Enfermedad Aguda , Animales , Arginina/farmacología , Ceruletida , Femenino , Depuradores de Radicales Libres/farmacología , Hepatopatías/patología , Hepatopatías/prevención & control , NG-Nitroarginina Metil Éster/farmacología , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , Pentoxifilina/farmacología , Ratas , Ratas WistarRESUMEN
The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 µg/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 ± 2.29, 20.89 ± 10.13, 11.52 ± 4.60, 18.69 ± 8.56, and 8.58 ± 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 ± 0.83, 1.09 ± 0.35, 2.05 ± 0.91, 1.70 ± 0.60, and 2.85 ± 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 ± 0.25, 0.33 ± 0.09, 0.37 ± 0.04, 0.34 ± 0.07 and 0.42 ± 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tissue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage.
Asunto(s)
Animales , Femenino , Ratas , Peroxidación de Lípido/efectos de los fármacos , Hepatopatías/etiología , Pancreatitis/complicaciones , Especies Reactivas de Oxígeno/metabolismo , Enfermedad Aguda , Arginina/farmacología , Ceruletida , Depuradores de Radicales Libres/farmacología , Hepatopatías/patología , Hepatopatías/prevención & control , NG-Nitroarginina Metil Éster/farmacología , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , Pentoxifilina/farmacología , Ratas WistarRESUMEN
CONTEXT: Some authors have found beneficial effect of statins in certain inflammatory conditions, but the effect of statins on acute pancreatitis is not yet defined. OBJECTIVE: The aim of this study was to evaluate the effect of simvastatin on an experimental model of mild and severe acute pancreatitis. ANIMALS: One hundred and one Wistar rats with cerulein or taurocholate-induced acute pancreatitis were used in this study. DESIGN: The rats were divided into two groups: Group I (n=51) received two previously i.p. injections (18+/-2 and 3+/-1 hours) of simvastatin (200 microg/kg) and Group II (n=50) received two previously i.p. injections of saline. Both groups were subdivided into two subgroups: mild pancreatitis (cerulein-induced; IA, n=10; IIA, n=10) and severe pancreatitis (taurocholate-induced; IB, n=41; IIB, n=40). MAIN OUTCOME MEASURES: The parameters evaluated were: pancreatic vascular permeability, tissue water content, histologic lesion, amylase serum levels in rats with mild pancreatitis (subgroups A); mortality rate, serum levels of IL-6, IL-10, amylase, pulmonary myeloperoxidase activity and ascitic levels of TNF-alpha in rats with severe pancreatitis (subgroups B). RESULTS: Serum levels of IL-10 were significantly lower in the simvastatin-treated group as well as the myeloperoxidase activity. There was no significant difference in any of other studied parameters. CONCLUSION: Simvastatin appears to reduce inflammatory cytokines and pulmonary neutrophilic activation in the severe acute pancreatitis model, but there is no significant effect on survival curve, in spite of a clear trend towards a better survival in the simvastatin group.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pancreatitis/tratamiento farmacológico , Simvastatina/uso terapéutico , Enfermedad Aguda , Animales , Ceruletida , Modelos Animales de Enfermedad , Interleucina-10/sangre , Interleucina-6/sangre , Pulmón/enzimología , Masculino , Pancreatitis/sangre , Pancreatitis/inducido químicamente , Peroxidasa/análisis , Ratas , Tasa de Supervivencia , Ácido Taurocólico , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Pancreatitis is a disease with high morbidity and mortality. In vitro experiments on pancreatic acini showed that supramaximal but not submaximal cholecystokinin (CCK) stimulation induces effects in the acinar cell that can be correlated with acinar morphological changes observed in the in vivo experimental model of cerulein-induced pancreatitis. The GTPase Rac1 was previously reported to be involved in CCK-evoked amylase release from pancreatic acinar cells. Here, we demonstrate that pretreatment with the Rac1 inhibitor NSC23766 (100 microM, 2 h) effectively blocked Rac1 translocation and activation in CCK-stimulated pancreatic acini, without affecting activation of its closely related GTPase, RhoA. This specific Rac1 inhibition decreased supramaximal (10 nM) CCK-stimulated acinar amylase release (27.% reduction), which seems to be connected to the reduction observed in serum amylase (46.6% reduction) and lipase levels (46.1% reduction) from cerulein-treated mice receiving NSC23766 (100 nmol h(-1)). The lack of Rac1 activation also reduced formation of reactive oxygen species (ROS; 20.8% reduction) and lactate dehydrogenase release (LDH; 24.3% reduction), but did not alter calcium signaling or trypsinogen activation in 10 nM CCK-stimulated acini. In the in vivo model, the cerulein-treated mice receiving NSC23766 also presented a decrease in both pancreatic and lung histopathological scores (reduction in oedema, 32.4 and 66.4%; haemorrhage, 48.3 and 60.2%; and leukocyte infiltrate, 53.5 and 43.6%, respectively; reduction in pancreatic necrosis, 65.6%) and inflammatory parameters [reduction in myeloperoxidase, 52.2 and 38.9%; nuclear factor kappaB (p65), 61.3 and 48.6%; and nuclear factor kappaB (p50), 46.9 and 44.9%, respectively], together with lower serum levels for inflammatory (TNF-alpha, 40.4% reduction) and cellular damage metabolites (LDH, 52.7% reduction). Collectively, these results suggest that pharmacological Rac1 inhibition ameliorates the severity of pancreatitis and pancreatitis-associated lung injury through the reduction of pancreatic acinar damage induced by pathological digestive enzyme secretion and overproduction of ROS.
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Enfermedades Pulmonares/metabolismo , Enfermedades Pulmonares/patología , Neuropéptidos/antagonistas & inhibidores , Pancreatitis/metabolismo , Pancreatitis/patología , Índice de Severidad de la Enfermedad , Proteínas de Unión al GTP rac/antagonistas & inhibidores , Aminoquinolinas/farmacología , Amilasas/metabolismo , Animales , Calcio/metabolismo , Membrana Celular/metabolismo , Ceruletida/efectos adversos , Ceruletida/farmacología , Colagogos y Coleréticos/efectos adversos , Colagogos y Coleréticos/farmacología , Colecistoquinina/efectos adversos , Colecistoquinina/análogos & derivados , Colecistoquinina/farmacología , Citosol/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Enfermedades Pulmonares/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C57BL , Neuropéptidos/efectos de los fármacos , Pancreatitis/inducido químicamente , Pirimidinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Unión al GTP rac/efectos de los fármacos , Proteína de Unión al GTP rac1RESUMEN
BACKGROUND: Hypothermia is a frequent event in severe acute pancreatitis (AP) and its real effects on the normal pancreas have not been well demonstrated. Moreover, neither have its effects on the outcome of acute pancreatitis been fully investigated. One hypothesis is that oxidative stress may be implicated in lesions caused or treated by hypothermia. AIM OF THE STUDY: To investigate the effect of hypothermia in cerulein-induced acute pancreatitis (CIAP) in rats and the role played by oxidative stress in this process. METHODS: Male Wistar rats were divided into hypothermic and normothermic groups. Hypothermia was induced with a cold mattress and rectal temperature was kept at 30 masculineC for one hour. Acute pancreatitis was induced with 2 doses of cerulein (20 ìg/kg) administered at a one-hour interval. Serum amylase, pancreas vascular permeability by Evan's blue method, pancreas wet-to-dry weight ratio and histopathology were analyzed in each group. RESULTS: When compared with normothermic rats, hypothermic animals, with cerulein-induced acute pancreatitis, showed higher levels of pancreatic vascular permeability (p < 0.05), pancreas wet-to-dry weight ratio (p = 0.03), and histologically verified edema (p < 0.05), but similar serum amylase levels. The hypothermic group showed a higher oxidized-reduced glutathione ratio than the normothermic group. CONCLUSION: Moderate hypothermia produced a greater inflammatory response in established acute pancreatitis induced by cerulein in rats. Moreover, this study suggests that oxidative stress may be one of the mechanisms responsible for the worse outcome in hypothermic rats with cerulein-induced acute pancreatitis.
Asunto(s)
Hipotermia/fisiopatología , Estrés Oxidativo/fisiología , Pancreatitis/fisiopatología , Enfermedad Aguda , Amilasas/sangre , Animales , Permeabilidad Capilar , Ceruletida , Glutatión/análisis , Masculino , Pancreatitis/inducido químicamente , Ratas , Ratas WistarRESUMEN
BACKGROUND: Hypothermia is a frequent event in severe acute pancreatitis (AP) and its real effects on the normal pancreas have not been well demonstrated. Moreover, neither have its effects on the outcome of acute pancreatitis been fully investigated. One hypothesis is that oxidative stress may be implicated in lesions caused or treated by hypothermia. AIM OF THE STUDY: To investigate the effect of hypothermia in cerulein-induced acute pancreatitis (CIAP) in rats and the role played by oxidative stress in this process. METHODS: Male Wistar rats were divided into hypothermic and normothermic groups. Hypothermia was induced with a cold mattress and rectal temperature was kept at 30°C for one hour. Acute pancreatitis was induced with 2 doses of cerulein (20 ìg/kg) administered at a one-hour interval. Serum amylase, pancreas vascular permeability by Evan's blue method, pancreas wet-to-dry weight ratio and histopathology were analyzed in each group. RESULTS: When compared with normothermic rats, hypothermic animals, with cerulein-induced acute pancreatitis, showed higher levels of pancreatic vascular permeability (p < 0.05), pancreas wet-to-dry weight ratio (p = 0.03), and histologically verified edema (p < 0.05), but similar serum amylase levels. The hypothermic group showed a higher oxidized-reduced glutathione ratio than the normothermic group. CONCLUSION: Moderate hypothermia produced a greater inflammatory response in established acute pancreatitis induced by cerulein in rats. Moreover, this study suggests that oxidative stress may be one of the mechanisms responsible for the worse outcome in hypothermic rats with cerulein-induced acute pancreatitis.
BACKGROUND: Hipotermia é um evento freqüente em episódios de pancreatite aguda, contudo seu efeito real sobre pâncreas normal ainda não esta bem demonstrado. Além do mais, o efeito da hipotermia no decorrer da pancreatite aguda também não está completamente esclarecido. Uma das hipóteses sobre as causas das lesões causadas ou tratadas por hipotermia aventa a implicação de estresse oxidativo. OBJETIVOS: Investigar o efeito da hipotermia em ratos com pancreatite aguda induzida por ceruleína e o papel do estresse oxidativo neste processo. MÉTODOS: Ratos Wistar machos foram divididos em grupos hipotérmicos e normotérmicos. Hipotermia foi induzida com uma bolsa gelada de forma que a temperatura retal permanecesse em 30°C por uma hora. Pancreatite aguda foi induzida com duas aplicações de ceruleína (20 ìg/kg) administradas com intervalo de uma hora. A amilase sérica, a permeabilidade vascular do pâncreas, a razão peso seco/peso úmido do pâncreas, a histopatologia e os níveis de glutationa foram analisados em cada grupo. RESULTADOS: Ratos hipotérmicos, com pancreatite aguda induzida por ceruleína, apresentaram maiores níveis de permeabilidade vascular no pâncreas (p < 0.05), razão peso seco/peso úmido do pâncreas (p = 0.03), e edema histológico (p < 0.05), mas os níveis de amilase sérica permaneceram iguais aos níveis apresentados pelos ratos normotérmicos. O grupo hipotérmico apresentou maior relação glutationa oxidada/glutationa reduzida em relação ao grupo normotérmico. CONCLUSÃO: Hipotermia moderada produziu uma maior resposta inflamatória em ratos com pancreatite aguda estabelecida, induzida por ceruleína, sugerindo que este efeito pode estar ligado a um maior índice de estresse oxidativo em ratos com pancreatite aguda.
Asunto(s)
Animales , Masculino , Ratas , Hipotermia/fisiopatología , Estrés Oxidativo/fisiología , Pancreatitis/fisiopatología , Enfermedad Aguda , Amilasas/sangre , Permeabilidad Capilar , Ceruletida , Glutatión/análisis , Pancreatitis/inducido químicamente , Ratas WistarRESUMEN
BACKGROUD: Recent studies indicate that hyperthermia can change inflammatory mechanisms and protect experimental animals from deleterious effects of secretagogue-induced acute pancreatitis AIM: To evaluate the effects of hyperthermia post-treatment on cerulein-induced acute pancreatitis in rats METHODS: Twenty animals were divided in two groups: group I (n = 10), rats with cerulein-induced acute pancreatitis undergone hyperthermia, and group II (n = 10), animals with cerulein-induced acute pancreatitis that were kept normothermic. In all groups, amylase serum levels, histologic damage, vascular permeability and pancreatic water content were assessed. Acute pancreatitis was induced by administration of two cerulein injections (20 mcg/kg). A single dose of Evans' blue dye was administered along with the second dose of cerulein. All animals also received a subcutaneous injection of saline solution. After this process, animals undergone hyperthermia were heated in a cage with two 100 W lamps. Body temperature was increased to 39.5°C and maintained at that level for 45 minutes. Normothermia rats were kept at room temperature in a second cage RESULTS: Control animals had typical edema, serum amylase activity and morphologic changes of this acute pancreatitis model. Hyperthermia post-treatment ameliorated the pancreatic edema, whereas the histologic damage and the serum amylase level remained unchanged CONCLUSIONS: The findings suggest a beneficial effect of the thermal stress on inflammatory edema in experimental acute pancreatitis.
RACIONAL: Estudos recentes indicam que a hipertermia pode modificar mecanismos inflamatórios e proteger animais experimentais dos efeitos deletérios da pancreatite aguda induzida por secretagogos OBJETIVO: Avaliar a eficácia da hipertermia como tratamento da pancreatite aguda induzida por ceruleína em ratos MÉTODOS: Vinte animais foram divididos em dois grupos: grupo I (n = 10), ratos com pancreatite aguda induzida por ceruleína e submetidos a hipertermia, e grupo II (n = 10), animais com pancreatite aguda induzida por ceruleína mantidos em normotermia. Em todos os grupos foram medidos níveis séricos de amilase, histologia, permeabilidade vascular e conteúdo de água do pâncreas. A pancreatite aguda foi induzida através da administração de duas injeções de ceruleína (20 mcg/ kg). Dose única do corante azul de Evans foi administrada juntamente com a segunda injeção de ceruleína. Todos os animais também receberam 5 mL de solução salina subcutânea. Após a indução, os animais do grupo hipertérmico foram aquecidos com duas lâmpadas de 100 W em gaiola parcialmente isolada. A temperatura corporal foi aumentada para 39,5°C e mantida neste nível por 45 minutos. Os animais controle foram mantidos em uma segunda gaiola em temperatura ambiente RESULTADOS: Os animais controle tiveram edema, danos histológicos e níveis de amilase típicos do modelo de pancreatite aguda leve com ceruleína. O tratamento com hipertermia melhorou o edema pancreático porém não teve efeito nos nível séricos de amilase e no dano histológico pancreático CONCLUSÕES: Os resultados sugerem efeito benéfico da hipertermia no edema inflamatório da pancreatite aguda leve experimental.
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Animales , Ratas , Edema/terapia , Hipertermia Inducida , Pancreatitis/terapia , Enfermedad Aguda , Amilasas/sangre , Temperatura Corporal/fisiología , Ceruletida , Modelos Animales de Enfermedad , Edema/prevención & control , Mediadores de Inflamación/análisis , Interleucina-1beta/análisis , /análisis , Pancreatitis/inducido químicamente , Ratas Wistar , Estadísticas no Paramétricas , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95% CI: 4.1-152 nM) and cerulein (EC50: 58; 95% CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG) reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95% CI: 2.5-18 microM) in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 microM L-NOARG from 73 +/- 5.1 to 19 +/- 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.
Asunto(s)
Ceruletida/farmacología , Colecistoquinina/farmacología , Duodeno/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fragmentos de Péptidos/farmacología , Receptores de Colecistoquinina/fisiología , Animales , Relación Dosis-Respuesta a Droga , Duodeno/fisiología , Masculino , Ratas , Ratas WistarRESUMEN
Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95 percent CI: 4.1-152 nM) and cerulein (EC50: 58; 95 percent CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG) reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95 percent CI: 2.5-18 æM) in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 æM L-NOARG from 73 ± 5.1 to 19 ± 3.5 percent in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.
Asunto(s)
Animales , Masculino , Ratas , Ceruletida/farmacología , Colecistoquinina/farmacología , Duodeno/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fragmentos de Péptidos/farmacología , Receptores de Colecistoquinina/fisiología , Relación Dosis-Respuesta a Droga , Duodeno/fisiología , Ratas WistarRESUMEN
AIMS: To study if the course of cerulein-induced pancreatitis in rats changes in a state of triglyceride-rich lipoprotein metabolism alteration. METHODS: Two groups of rats received control diet during a 90-day period (A) and sucrose-rich diet to induce endogenous hypertriglyceridemia (B). Subgroups A2 and B2 received i.p. 45 microg cerulein/kg body weight (to induce acute pancreatitis). Histological examination of pancreas tissue, serum pancreatic lipase, lipoprotein profile and VLDL chemical composition were assessed. Then, pancreatic lipase hydrolytic activity on VLDL-triglycerides was evaluated in vitro. RESULTS: Cellular vacuolization was observed in all of the cerulein-injected rats, but only in subgroup B2 fat necrosis was present. Serum triglycerides were higher in subgroup B1 than in subgroup A1 (mean +/- SEM, mg/dl 123,77 +/- 25.7 vs. 65.8 +/- 7, p < 0.01). Triglycerides from rats fed with sucrose-rich diet, decreased after cerulein-induced pancreatitis (80.38 +/- 11.3 vs. 123,77 +/- 25.7, p < 0.02). Moreover, the endogenous hypertriglyceridemic rats showed an increment of VLDL triglyceride content, which decreased when rats were injected with cerulein. A negative correlation was found between VLDL-triglyceride content and serum pancreatic lipase activity (r = 0.58, p < 0.02). The in vitro assay showed a decrease in VLDL-triglyceride content post incubation with pancreatic lipase enriched serum (mean +/- SD: 59.2 +/- 27.7%, p < 0.01). CONCLUSIONS: The endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis and it could be related to the decrease in VLDL-triglycerides as a consequence of pancreatic lipase hydrolytic activity.