Ethanol-induced alterations of matrix network in the duodenal mucosa of chronic alcohol abusers

Abstract

Excessive consumption of alcoholic beverages may be associated with gastrointestinal symptoms, including dyspepsia and diarrhoea. It is not clear whether or not chronic alcohol ingestion damages the mucosa of the small intestine. We investigated the effect of chronic alcohol abuse on the duodenal mucosa, and particularly on its extracellular matrix (ECM) network. Duodenal biopsy specimens were obtained during upper gastrointestinal endoscopy from 50 chronic alcoholics without cirrhosis and 10 healthy subjects. Morphological studies were performed by routine histology, immunohistochemistry and electron microscopy. Morphometry of duodenal tissues was performed with a computerized image analyser. No significant duodenal epithelial changes were found in alcoholics, despite an evident reduction in the enterocyte turnover. Myofibroblast-like cells were significantly increased in the villus stroma of alcoholics in comparison to controls. These cells stained positively for desmin, alpha-smooth muscle actin and for several ECM components. In alcohol abusers the thickness of the mucosal basement membrane was greater and the staining for collagen I and III was enhanced both in the basement membrane and in the villus stroma. A higher expression of tenascin was also seen at the base of villi of alcoholics. Chronic alcohol abuse may induce fibrosis of duodenal villi which is associated with a transformation of villus juxta-parenchymal cells into active subepithelial myofibroblast-like cells able to produce different ECM components.

Repeated ethanol exposure during late gestation alters the maturation and innate immune status of the ovine fetal lung

“…Prenatal ethanol exposure increases the expression of COLIA1 in the fetal lung and the deposition of collagen fibers types I and III, which constitute ϳ90% of the collagens within the lung (10). These findings are similar to studies in adults that have shown that alcohol consumption results in increased procollagen type I expression in the liver, duodenum, and pancreas, resulting in fibrosis in these organs (11,12,46). An increase in collagen deposition in the lung is also associated with pulmonary fibrosis, which reduces lung distensibility, which in turn decreases forced expiratory volume and forced vital capacity (10).…”

Acute ethanol exposure impairs angiogenesis and the proliferative phase of wound healing

“…Hydroxyproline, used as an index for total collagen content, was significantly reduced at day 7 postwounding in wounds from ethanol-treated animals compared with saline controls (5.94 Ϯ 1.56 vs. 9.43 Ϯ 0.56 g/mg wet wt). These results are consistent with previous in vitro observations in which ethanol exposure inhibited collagen synthesis by fibroblasts and increased levels of matrix-degrading proteins (4,21,34). Although these data do not reveal the mechanism, it is evident that acute ethanol exposure significantly impairs the regeneration of the dermal extracellular matrix.…”

Acute ethanol exposure disrupts VEGF receptor cell signaling in endothelial cells

“…Ethanol is predominantly oxidized by ADH into acetaldehyde, which is further metabolized into acetate. Acetaldehyde is believed to induce numerous cellular alterations via increases in ROS, RNA and protein stability, and receptor levels (1,9,16,28,41). In vivo experiments using t-butanol, a tertiary long-chain alcohol known to increase membrane fluidity, did not induce changes in vascular density nor hydroxyproline content, suggesting that increasing membrane fluidity in and of itself would not inhibit wound angiogenesis.…”