Ethanol Feeding Aggravates Morphological and Biochemical Parameters in Experimental Chronic Pancreatitis

Abstract

Background and Aims: 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.

Assessment of the protective effects of oral tocotrienols in arginine chronic-like pancreatitis

“…Some other experimental models induce the development of chronic-like pancreatitis after surgical manipulations (35), after administration of toxic compounds that also affect other organs (43), or under specific genetic backgrounds (29). We chose to test tocotrienols on the rat model of pancreatic damage induced by repeated arginine pancreatitis on the basis of previously published work and on our own observations (Figs.…”

“…Of notice, hydroxyproline levels did not correlate with fibrosis area fraction, pancreatic weight, lacunarity, or fractal dimension, parameters that give good estimates of chronic pancreatic damage. This apparent contradiction can be explained by the fact that hydroxyproline measurements are high when fibrosis is present but also when collagenase activity is increased, as in tissue remodeling evolving in normal wound healing (35,53). Therefore, hydroxyproline may not always accurately reflect the fibrotic burden of the tissue.…”

“…Biochemical determination of hydroxyproline in tissue samples is widely used as a surrogate for total collagen. However, hydroxyproline may also be the result of increased collagenase activity, as it occurs in tissue remodeling (35,53). An indirect approach to estimate chronic pancreatic damage is the determination of elements actively involved in fibrogenesis, such as cytokines and growth factors (TGF-␤, PDFG, and monocyte chemoattractant protein) and cytofilaments overexpressed by activated PSCs (␣-SMA).…”

Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis

“…The severity of CP was assessed by a previously described histological grading system that uses a semiquantitative score on a scale of 0 -3 for glandular atrophy, fibrosis, and inflammatory infiltrate (7,16).…”

Animal Models in Alcoholic Pancreatitis — What Can We Learn?

“…Chronic alcohol feeding has been investigated in combination with pancreatic duct obstruction [59,60], with instillation of trinitrobenzene sulfonic acid (TNBS) [61], with administration of a single dose of dibutyltin dichloride (DBTC) [62], with additional feeding of acetylsalicylic acid (ASA) [49], with application of a single dose of endotoxin [63], and with infusion of a low dose of cholecystokinine [64].…”