RESUMO
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.
Assuntos
Pancreatite , Triterpenos , Ratos , Animais , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ceruletídeo , Ratos Wistar , Doença Aguda , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Ácido UrsólicoAssuntos
Vacinas contra COVID-19 , COVID-19 , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Hepatite , Pancreatite , Humanos , COVID-19/prevenção & controle , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/complicações , Eosinofilia/complicações , Hepatite/complicações , Pancreatite/induzido quimicamente , Pancreatite/complicações , VacinaçãoRESUMO
Abstract Acute pancreatitis (AP) is a life-unpleasant situation with contradictory and inadequate treatments. In this regard, the present study evaluated the effect of the possible pretreatment of lipase-pancreatin on L-arginine-induced AP. Forty adult mice were selected and divided into five groups: I) control group, II and III) AP groups (i.p.) receiving L-arginine of 2×300 and 2×400 mg/100 g body weight (b.w.), IV) AP (2×300 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase), and V) AP (2×400 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase). All AP groups displayed a significant increase in serum levels of ALT, AST, TBARS, and TNF-alpha compared to the control group. Moreover, pancreatic tissue edema, inflammation, and vacuolization of acinar cells were significantly higher in the untreated L-arginine group compared to the control and pancreatin groups. Conversely, the diameter of pancreatic islets significantly declined after induction of pancreatitis compared with control and pancreatin groups. Pancreatin treatment can be used in pancreatic dysfunction, however, this medicine showed no protective effect against L-arginine-induced AP in the mouse model.
Assuntos
Animais , Masculino , Camundongos , Pancreatite/induzido quimicamente , Pancreatina/efeitos adversos , Fator de Necrose Tumoral alfa/agonistas , Células Acinares/classificaçãoRESUMO
PURPOSE: Brazil nuts (Bertholletia excelsa) are consumed world-wide and have become a new trend in weight loss supplementation. We present a unique case of severe hypertriglyceridemia-associated acute pancreatitis following daily usage of a Brazil nut supplement product. SUMMARY: A Hispanic female presented with severe hypertriglyceridemia and acute pancreatitis several months after starting a Brazil nut weight loss supplement in the setting of poorly controlled Type 2 Diabetes Mellitus. Her initial triglyceride level was undetectably high >10,000 mg/dL but improved rapidly following euglycemic insulin infusion and supplement cessation. The patient was managed with supportive care, started on oral fibrate therapy after abdominal symptoms improved, and was discharged to home in stable condition. CONCLUSION: It is essential for pharmacists to maintain a high index of suspicion for patients taking complementary and alternative medications and supplements who present with acutely altered laboratory parameters or onset of acute disease. In this instance, a patient was found to have profound hypertriglyceridemia with onset of acute pancreatitis following usage of a Brazil nut weight loss supplement.
Assuntos
Bertholletia , Diabetes Mellitus Tipo 2 , Hipertrigliceridemia , Pancreatite , Humanos , Feminino , Pancreatite/induzido quimicamente , Pancreatite/diagnóstico , Doença Aguda , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipertrigliceridemia/induzido quimicamente , Hipertrigliceridemia/complicações , Suplementos Nutricionais/efeitos adversos , Redução de PesoRESUMO
Lectins isolated from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) are promising molecules to prevent cell death. Acute pancreatitis, characterized by acinar cell necrosis and inflammation, presents significant morbidity and mortality. This study has investigated the effects of ConA and ConBr in experimental acute pancreatitis and pancreatic acinar cell death induced by bile acid. Pancreatitis was induced by retrograde pancreatic ductal injection of 3% sodium taurocholate (Na-TC) in male Swiss mice. ConA or ConBr (0.1, 1 or 10 mg/kg) were intravenously applied to mice 1 h and 12 h after induction. After 24 h, the severity of pancreatitis was evaluated by serum amylase and lipase, histopathological changes and myeloperoxidase assay. Pancreatic acinar cells were incubated with ConA (200 µg/ml) or ConBr (200 µg/ml) and taurolithocholic acid 3-sulfate (TLCS; 500 µM). Necrosis and changes in mitochondrial membrane potential (ΔÑ°m) were detected by fluorescence confocal microscopy. Treatment (post-insult) with ConA and ConBr decreased pancreatic damage caused by retrograde injection of Na-TC in mice, reducing pancreatic neutrophil infiltration, edema and necrosis. In addition, ConA and ConBr decreased pancreatic acinar cell necrosis and depolarization of ΔÑ°m caused by TLCS. The inhibition of necrosis was prevented by the lectin domain blockade. In conclusion, ConA and ConBr markedly inhibited in vitro and in vivo damage, effects partly dependent on the interaction with mannose residues on acinar cells. These data support the potential application of these proteins for treatment of acute pancreatitis.
Assuntos
Canavalia , Pancreatite , Doença Aguda , Animais , Anti-Inflamatórios , Canavalia/química , Lectinas/farmacologia , Masculino , Camundongos , Necrose/tratamento farmacológico , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Lectinas de Plantas/química , Sementes/químicaRESUMO
ABSTRACT: We report a case of acute pancreatitis that developed after four days of remdesivir therapy in a patient being treated for COVID-19. Despite improvement in patient's respiratory status, abdominal pain worsened and clinical signs and symptoms progressed to a diagnosis of acute pancreatitis 4 days after initiation of remdesivir therapy. Withdrawal of remdesivir paired with medical management of acute pancreatitis led to the resolution of pancreatitis within three days. To our knowledge, this is the first case report depicting remdesivir as a possible cause of acute pancreatitis.
Assuntos
Tratamento Farmacológico da COVID-19 , Pancreatite , Doença Aguda , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Humanos , Pancreatite/induzido quimicamente , Pancreatite/diagnósticoRESUMO
Acute pancreatitis (AP) is an inflammatory disease associated with abdominal pain and elevated serum pancreatic enzymes. The most common etiologies are gallstones and alcoholism. Drug-induced AP is quite rare, lacks a solid understanding and has been occasionally reported. The diagnosis requires a great suspicion and a careful exclusion of other causes. We present a case of a 37-year-old man, previously diagnosed with leprosy that developed acute pancreatitis after starting the multibacillary polychemotherapy (PCT/MB). After a month of treatment and the discontinuation of the PCT/MB, the therapy was restarted and a new episode of AP occurred. Three months after this last episode, the PCT/MB was reintroduced, changing one of the medications and the patient had no recurrence of AP or other reactions. Therefore, it is important to take into account that there is a risk of acute pancreatitis in patients on multidrug therapy (MDT) for leprosy.
Assuntos
Hanseníase Multibacilar , Hanseníase , Pancreatite , Doença Aguda , Adulto , Quimioterapia Combinada , Humanos , Hansenostáticos/efeitos adversos , Hanseníase/complicações , Hanseníase/tratamento farmacológico , Masculino , Pancreatite/induzido quimicamenteRESUMO
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.
Assuntos
Dor Abdominal/prevenção & controle , Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Hiperalgesia/prevenção & controle , Limiar da Dor/efeitos dos fármacos , Pancreatite/prevenção & controle , Dor Abdominal/etiologia , Dor Abdominal/metabolismo , Dor Abdominal/fisiopatologia , Animais , Comportamento Animal/efeitos dos fármacos , Canais de Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Ceruletídeo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Mediadores da Inflamação/metabolismo , Masculino , Neuropeptídeos/farmacologia , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Pancreatite/fisiopatologia , Ratos Wistar , Venenos de Aranha/farmacologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , ômega-Conotoxinas/farmacologiaRESUMO
The relationship between acute pancreatitis and the administration of glucocorticoids is unclear because most reported cases have been diagnosed with systemic vascular diseases, such as systemic lupus erythematosus, which may be responsible for pancreatitis. A 22-year-old woman with eye involvement of a newly diagnosed systemic lupus erythematosus was admitted to our hospital. Pulse intravenous methylprednisolone therapy was given at 1mg/kg day for 3 days, and oral prednisolone at 40 mg/day thereafter. During pulse steroid therapy, she had abdominal pain, back pain, distention, nausea, and vomiting. Her physical examination was compatible with acute abdomen and peritonitis. Abdomen Computerized Tomography scan revealed diffuse liquid perihepatic and perisplenic area with heterogeneity around the mesentery. Due to the symptoms of acute abdomen, explorative laparotomy was performed. There was diffuse free fluid in the abdomen and edematous changes were observed around the pancreas. Amylase and lipase from intraabdominal fluid were studied and found to be high. The postoperative prednol dose was reduced carefully. On the sixth postoperative day, the drain was removed, and the patient was discharged without any problem. Physicians should keep in mind that acute pancreatitis may also be a cause of differential diagnosis of newly developed abdominal pain in patients receiving pulse steroid therapy with a normal level of serum amylase and lipase.
Assuntos
Lúpus Eritematoso Sistêmico , Pancreatite , Doença Aguda , Corticosteroides , Feminino , Humanos , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/complicações , Metilprednisolona/efeitos adversos , Pancreatite/induzido quimicamente , Adulto JovemRESUMO
SUMMARY The relationship between acute pancreatitis and the administration of glucocorticoids is unclear because most reported cases have been diagnosed with systemic vascular diseases, such as systemic lupus erythematosus, which may be responsible for pancreatitis. A 22-year-old woman with eye involvement of a newly diagnosed systemic lupus erythematosus was admitted to our hospital. Pulse intravenous methylprednisolone therapy was given at 1mg/kg day for 3 days, and oral prednisolone at 40 mg/day thereafter. During pulse steroid therapy, she had abdominal pain, back pain, distention, nausea, and vomiting. Her physical examination was compatible with acute abdomen and peritonitis. Abdomen Computerized Tomography scan revealed diffuse liquid perihepatic and perisplenic area with heterogeneity around the mesentery. Due to the symptoms of acute abdomen, explorative laparotomy was performed. There was diffuse free fluid in the abdomen and edematous changes were observed around the pancreas. Amylase and lipase from intraabdominal fluid were studied and found to be high. The postoperative prednol dose was reduced carefully. On the sixth postoperative day, the drain was removed, and the patient was discharged without any problem. Physicians should keep in mind that acute pancreatitis may also be a cause of differential diagnosis of newly developed abdominal pain in patients receiving pulse steroid therapy with a normal level of serum amylase and lipase.
RESUMO A relação entre pancreatite aguda e a administração de glicocorticoides é incerta pois a maioria dos casos relatados foram diagnosticados com doenças vasculares sistêmicas, como lúpus eritematoso sistêmico, que pode causar pancreatite. Uma paciente de 22 anos com envolvimento ocular e lúpus eritematoso sistêmico recém-diagnosticado foi admitida em nosso hospital. Pulsoterapia intravenosa com metilprednisolona 1mg/kg foi administrada por 3 dias. Depois disso, a paciente foi tratada com prednisolona oral 40 mg/dia. Durante a pulsoterapia com corticoides, a paciente apresentava dor abdominal, dor nas costas, distensão, náusea e vômitos. O exame físico era compatível com quadro de abdome agudo e peritonite. Tomografia computadorizada do abdome revelou líquido difuso na região perihepática e periesplênica, com heterogeneidade ao redor do mesentério. Devido aos sintomas de abdome agudo, foi realizada laparotomia exploradora. Havia líquido livre difuso no abdome e alterações edematosas foram observadas em torno do pâncreas. A amilase e lipase do líquido intra-abdominal foram analisadas e consideradas elevadas. A dose pós-operatória de prednol foi reduzida com cuidado. No sexto dia de pós-operatório, o dreno foi retirado, e a paciente recebeu alta sem qualquer problema. Médicos devem lembrar que a pancreatite aguda também pode ser uma causa de diagnóstico diferencial para dor abdominal recém-desenvolvida em pacientes recebendo pulsoterapia com corticoides e com níveis normais de amilase e lipase séricas.