Do the Effects of Pentoxifylline on the Inflammatory Process and Pancreatic Infection Justify Its Use in Acute Pancreatitis?

Matheus, André Siqueira; Coelho, Ana Maria M.; Sampietre, Sandra N.; Jukemura, José; Patzina, Rosely Antunes; Cunha, José Eduardo Monteiro da; Machado, Marcel Cerqueira César

doi:10.1159/000199438

Cited by 15 publications

(17 citation statements)

References 37 publications

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“…Our group has also demonstrated the beneficial effect o PTX administration at the time of AP induction 16 . In the present study we observed that PTX administered after the onset of AP effectively inhibited the production of TNF-α and IL-6, which are AP markers and whose levels correlate with the severity of the disease.…”

Section: Ptx Effect On Mortality Studymentioning

confidence: 66%

“…In previous experimental studies we have demonstrated that in this rat model of AP using sodium taurocholate the highest levels of inflammatory cytokines occurs between 2 and 4 h after AP induction therefore 1 hour is an appropriate length of time to start the treatment 16 .…”

Section: Pentoxifylline and Saline Administrationmentioning

confidence: 79%

“…Studies from our group have demonstrated that administration of PTX in rats with taurocholic acid-induced AP reduced local and systemic inflammatory responses and decreased pancreatic infection and mortality rate 16 . However, administration of this drug in these studies was done at the time of AP induction, which is unrealistic in a clinical setting where patients already have developed systemic inflammation.…”

Section: Introductionmentioning

confidence: 92%

“…Treatment of AP with PTX has shown to be beneficial in the experimental management of this disease, however administration of this drug in these studies was done at the time of AP induction [13][14][15][16] . In an experimental model of severe AP, evaluating the effect of administration of PTX after the onset of AP, no changes of the hemodynamic parameters and mortality rate were observed however, in this study inflammatory parameters…”

Section: Ptx Effect On Mortality Studymentioning

confidence: 99%

“…Treatment of AP with PTX has shown to be beneficial in the experimental management of this disease [13][14][15][16] . Studies from our group have demonstrated that administration of PTX in rats with taurocholic acid-induced AP reduced local and systemic inflammatory responses and decreased pancreatic infection and mortality rate 16 .…”

Section: Introductionmentioning

confidence: 99%

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Is there a therapeutic window for pentoxifylline after the onset of acute pancreatitis?

Coelho¹,

Kunitake

Machado³

et al. 2012

Acta Cir. Bras.

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PURPOSE:To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP. Key words: Acute Pancreatitis; Pentoxifylline; Inflammation; Cytokines; Systemic Inflammatory Response RESUMO OBJETIVO: Investigar os efeitos da pentoxifilina (PTX) na pancreatite aguda (PA) experimental administrando a droga após a indução da doença. MÉTODOS: Cem ratos machos Wistar foram submetidos à indução da PA através da infusão de taurocolato de sódio e divididos em três grupos: Grupo Sham: sham-operated ratos, Grupo Salina: AP e solução salina, e Grupo PTX: AP e PTX. Solução salina e PTX foram administradas 1 hora após a indução da PA. Três horas após indução da PA os níveis de fator de necrose tumoral (TNF)-α no líquido peritoneal e os níveis séricos de interleucina (IL)-6 e IL-10 foram analisados pelo método de Enzima Imunoensaio (ELISA). A atividade da mieloperoxidase (MPO) foi analisada no pulmão e foram realizadas análises histológicas do pulmão e pâncreas, além do estudo da mortalidade. RESULTADOS: A administração de PTX 1 hora após a indução da PA reduziu significativamente os níveis de TNF-α peritoneal e os níveis séricos de IL-6 e IL-10 quando comparado ao grupo salina. Redução na mortalidade foi observado após o tratamento com PTX comparado ao grupo salina. CONCLUSÃO: A administração de PTX após a indução da PA diminuiu os níveis sistêmicos de citocinas pró-inflamatórias, sugerindo a possibilidade de que existe uma janela terapêutica para PTX após o início do PA.

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Section: Ptx Effect On Mortality Studymentioning

confidence: 66%

Section: Pentoxifylline and Saline Administrationmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 92%