Ethanol feeding aggravates morphological and biochemical parameters in experimental chronic pancreatitis.
OBJECTIVE
Instillation of trinitrobenzene sulfonic acid (TNBS) into the rat pancreatic ducts induces morphological changes resembling human chronic pancreatitis. In humans, alcoholism is commonly associated with chronic pancreatitis, but ethanol feeding fails to induce pancreatitis in experimental animals. We hypothesized that ethanol would manifest its pathogenetic effects on a duct-injured pancreas.


METHODS
Chronic pancreatitis was induced in rats by instillation of TNBS into pancreatic ducts. Thereafter, rats were fed a normal chow diet with or without ethanol supplementation. Control rats received vehicle and a normal diet. A separate group of vehicle-treated rats were also fed with ethanol. At 2 and 4 weeks pancreata were excised and processed for morphological examination or for biochemical assays. From crude homogenates, protein and hydroxyproline were quantified. After sonication, homogenates were also assayed for amylase and DNA. An oral glucose tolerance test was performed on the fourth week.


RESULTS
TNBS induced chronic fibrogenic pancreatitis that was associated with a reduction in pancreatic weight, DNA, protein and amylase as compared to control rats. Ethanol feeding to TNBS-treated animals slowed weight gain, increased fasting glucose and impaired glucose tolerance test. Larger areas of gland atrophy were observed with a striking disruption of the normal architecture of the islets. Ethanol accelerated pancreatic involution and collagen deposition as measured by total amylase, protein, DNA and hydroxyproline content.


CONCLUSIONS
In TNBS chronic pancreatitis, active fibrogenesis is associated with progressive atrophy of glandular elements. Morphological and biochemical parameters are aggravated by sustained ethanol intake.
Puig-Diví
V
V
Digestive System Research Unit, Hospital General Universitari Vall d'Hebron, Barcelona, Spain.
Molero
X
X
Vaquero
E
E
Salas
A
A
Guarner
F
F
Malagelada
J
J
D000681:Amylases / Q000032:analysis; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D002908:Chronic Disease; D004247:DNA / Q000032:analysis; D000431:Ethanol / Q000633:toxicity*; D005951:Glucose Tolerance Test; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage
D011506:Proteins; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid; D004247:DNA; D000681:Amylases; D006909:Hydroxyproline