Intestinal mucosal alterations in rats with carbon tetrachloride-induced cirrhosis: Changes in glycosylation and luminal bacteria

Abstract

Spontaneous bacterial peritonitis is a major cause of mortality after liver cirrhosis. Altered permeability of the mucosa and deficiencies in host immune defenses through bacterial translocation from the intestine due to intestinal bacterial overgrowth have been implicated in the development of this complication. Molecular mechanisms underlying the process are not well known. In order to understand mechanisms involved in translocation of bacteria, this study explored the role of oxidative stress in mediating changes in intestinal mucosal glycosylation and luminal bacterial content during cirrhosis. CCl 4 -induced cirrhosis in rats led to prolonged oxidative stress in the intestine, accompanied by increased sugar content of both intestinal brush border and surfactant layers. This was accompanied by changes in bacterial flora in the gut, which showed increased hydrophobicity and adherence to the mucosa. Inhibition of xanthine oxidase using sodium tungstate or antioxidant supplementation using vitamin E reversed the oxidative stress, changes in brush border membrane sugar content, and bacterial adherence. In conclusion, oxidative stress in the intestine during cirrhosis alters mucosal glycosylation, accompanied by an increased hydrophobicity of luminal bacteria, enabling increased bacterial adherence onto epithelial cells. This might facilitate translocation across the mucosa, resulting in complications such as spontaneous bacterial peritonitis. (HEPATOLOGY 2006;43:837-846.)

Role of Oxygen Free Radicals, Nitric Oxide and Mitochondria in Mediating Cardiac Alterations During Liver Cirrhosis Induced by Thioacetamide

“…Liver cirrhosis can induce functional alterations in the intestine [13,14] and kidney [15] due to oxidant stress, which has also been demonstrated in mice cardiac cells after bile duct ligation [34]. Our data now show that elevations in protein carbonyl and malondialdehyde are evident in the heart before development of frank cirrhosis in the liver after TAA administration.…”

“…Oxygen free radicals have been implicated in the pathogenesis of toxic liver injury [12], and oxidative stress during liver cirrhosis is responsible for intestinal and renal damage [13][14][15]. Oxidative stress has been suggested to be involved in cardiac dysfunction in the cirrhotic heart [16], and an increase in lipid peroxidation markers has been demonstrated in the kidney, brain and heart of rats with cholestatic liver disease suggesting oxidative damage to different organs [17].…”

Potential ProbioticEscherichia coli16 Harboring theVitreoscillaHemoglobin Gene Improves Gastrointestinal Tract Colonization and Ameliorates Carbon Tetrachloride Induced Hepatotoxicity in Rats

“…Carbon tetrachloride (CCl 4 ) causes tissue injury especially in hepatocytes by the formation of reactive trichloromethyl radicals [23]. Trichloromethyl radical reacts with molecular oxygen to form trichloromethylperoxyl radical and oxidizes lipid molecules by hydrogen abstraction especially in hepatocytes.…”

Role of Translocation of Pathogen-Associated Molecular Patterns in Sepsis

“…Subsequently, bacterial translocation has been recognized as a possible major contributor to the development of systemic infection and multiple organ dysfunction after shock, mechanical trauma, or thermal injury, as well as in ICU patients. Numerous experimental studies using animal models of trauma [3], thermal injury [4,5,6], hemorrhagic shock [7, 8], intestinal obstruction [9], obstructive jaundice [10, 11], and liver cirrhosis [12, 13] have shown that bacterial translocation occurs commonly in various situations. In humans, there is also increasing evidence for bacterial translocation under specific conditions as listed in table 1.…”