endothelin-1 and Pancreatitis--Chronic

The aim of this study is to prove the influence of tobacco smoking on the endothelin-1 (ET-1) level in the plasma and on the immunohistochemical localization in the pancreatic tissues. The blood was collected from 50 healthy individuals and 63 patients with chronic pancreatitis (CP). The ET-1 and cotinine concentrations in the plasma were estimated by ELISA. Samples of tissues of the normal pancreas and CP were verified histopathologically, and then ET-1 was localized by immunohistochemical staining using the monoclonal anti-human ET-1 antibody. The intensity of immunohistochemical reaction was calculated with the semiquantitative Digital Imaging Methodology. The study demonstrated a significant concentration of ET-1 in smoking healthy individuals and in patients with CP when compared with the nonsmoking population (P=0.003 and 0.0005, respectively). A significantly stronger immunohistochemical ET-1 reaction was observed in the tissue of smoking patients with CP than in the normal pancreatic tissue and of nonsmoking CP patients (P=0.001, 0.008, and 0.03, respectively). The presented data evidence that tobacco smoking has a direct effect on the endothelium, leading to an increased level of ET-1.

Topics: Adult; Aged; Endothelin-1; Female; Humans; Male; Middle Aged; Pancreas; Pancreatitis, Chronic; Smoking

The pathogenesis of chronic pancreatitis (CP) is a complex process of interaction between tissue injury and repair, which involves microcirculatory disturbance. Amygdalin, an effective component extracted from Semen Persicae (a kind of Chinese herbal medicine), can decrease blood viscosity and improve microcirculation. In this study, we investigated the therapeutic effects of amygdalin on pancreatic fibrosis in rats with CP.. The rat CP model was induced by injecting dibutyltin dichloride (DBTC) into the right caudal vein. Amygdalin was administrated via the penile vein at a dose of 10 mg/(kg d) from the next day, after the induction of CP, once a day for the previous 3 days, and then once every 2 days, until the end of the experiment. Body weight was observed every 7 days. Pancreatic blood flow and histopathological changes were assessed at 28 days. The activation of pancreatic stellate cells (PSCs) was estimated by the expression of α-smooth muscle actin (α-SMA). At the same time, the expression of platelet-derived growth factor-BB (PDGF-BB), transforming growth factor β-1 (TGFβ-1), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP) of pancreatic tissues were detected.. Treatment of CP rats with amygdalin improved body weight and pancreatic blood flow, as well as alleviated pancreatic fibrosis and acinar destruction, accompanied by the down-regulation of the expressions of α-SMA, PDGF-BB, TGFβ-1, and ET-1, and the up-regulation of the CGRP's expression.. Amygdalin could reduce the production of pro-fibrotic cytokines, inhibit the activation of PSCs, and attenuate pancreatic fibrosis in a rat with CP. The mechanism probably includes improving microcirculatory disturbance by regulating the production of ET-1 and CGRP.

Topics: Actins; Amygdalin; Animals; Becaplermin; Calcitonin Gene-Related Peptide; Endothelin-1; Fibrosis; Gene Expression Regulation; Male; Microcirculation; Pancreas; Pancreatic Stellate Cells; Pancreatitis, Chronic; Rats; Rats, Wistar

Pancreatic stellate cells (PSC) play a key role in pancreatic fibrosis. Activation of PSC occurs in response to pro-fibrogenic stimuli and is maintained by autocrine loops of mediators, such as endothelin (ET)-1. Here, we have evaluated effects of the dual ET receptor antagonist bosentan in models of pancreatic fibrogenesis and cancer. Cell culture studies revealed that PSC and DSL6A pancreatic cancer cells expressed both ET-1 and ET receptors. Bosentan efficiently inhibited proliferation of both cell types and collagen synthesis in PSC. Expression of the myofibroblastic marker alpha-smooth muscle actin, connective tissue growth factor, and ET-1 itself in PSC was reduced, while expression of matrix metalloproteinase-9 was enhanced. Like PSC, DSL6A cells secrete less ET-1 when cultured with bosentan. In a rat model of pancreatic fibrosis, chronic pancreatitis induced by dibutyltin dichloride, a tendency towards a diminished disease progression was observed in a subgroup of rats with less severe disease. Together, our results indicate that bosentan exerts antifibrotic and antitumor effects in vitro. Its efficiency in vivo warrants further investigation.

Topics: Animals; Bosentan; Carcinoma; Cell Line, Tumor; Coculture Techniques; Collagen; Endothelin Receptor Antagonists; Endothelin-1; Fibrosis; Organotin Compounds; Pancreas; Pancreatic Neoplasms; Pancreatitis, Chronic; Rats; Receptors, Endothelin; Sulfonamides