Prevention of Acute Pancreatitis by Broccoli Components

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Nutritional Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Araya Roldan, Marcela Maria

Contributors dc:contributor

• Sharon Donovan

• Health Sciences, Nutrition

Language dc:language

eng

Identifier

(MiAaPQ)AAI3314724

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84954