Prevention of Acute Pancreatitis by Broccoli Components
Araya Roldan, Marcela Maria
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Permalink
https://hdl.handle.net/2142/84954
Description
Title
Prevention of Acute Pancreatitis by Broccoli Components
Author(s)
Araya Roldan, Marcela Maria
Issue Date
2008
Doctoral Committee Chair(s)
Sharon Donovan
Department of Study
Nutritional Sciences
Discipline
Nutritional Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Nutrition
Language
eng
Abstract
Acute pancreatitis is a common and refractory inflammatory disease affecting pancreatic acinar cells. Annually 300,000 patients are hospitalized. Attempts to halt the progression of the disease with anti-inflammatory drugs once pancreatitis has developed have been inconsistent. One promising area of research is preventive intervention by early inhibition of nuclear factor-kappaB (NF-kappaB). Cholecystokinin (CCK)-induced acute pancreatitis is the most widely used in vivo experimental model, with a similar inflammation profile to acute pancreatitis in humans. Administration of crambene (1-cyano-2S-hydroxy-3-butene, CHB) to male F344 rats upregulates both glutathione synthesis and apoptosis in pancreas. Furthermore, studies conducted in CD-1 mice suggest that induction of apoptosis by acute iv CHB may reduce the severity of experimental acute pancreatitis. Therefore, we hypothesized that dietary pretreatment of male F344 rats with crambene will ameliorate acute pancreatitis by inhibiting inflammatory mediators. Cholecystokinin (100 mg/kg s-c x 2, one h apart) caused significantly elevated serum amylase (3-fold) and lipase (8-fold) 2 and 4 h after the last injection, confirming pancreatitis. Administration of crambene (300 and 600 mumol/kg) 12 h prior to CCK, significantly reversed the elevation in the serum amylase and lipase activities to 1.5-fold and 1.1-fold, respectively (p<0.05). Crambene at 1000 mumol/kg was slightly less effective possibly suggesting toxicity of the CHB. Crambene also decreased the CCK-induced elevation in the pancreatic pro-inflammatory cytokines IL-6 and TNF-alpha. To evaluate whether the biological effects of CHB on amelioration of pancreatitis can be obtained through consumption of cruciferous vegetables, a 10% broccoli diet was given to rats. Because CHB has some of the same actions as sulforaphane, this was also compared to CHB to determine if it would ameliorate pancreatitis. Administrations of broccoli and sulforaphane have similar effects as CHB. Although none of the treatments given prevented the degradation of IkappaBalpha, CHB, sulforaphane and a 10% Broccoli diet all ameliorated CCK-induced acute pancreatitis by inhibiting NF-kappaB activity. Overall, these data suggest that there is preliminary evidence that consumption of broccoli could be used as a preventive treatment to reduce the severity of acute pancreatitis.
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