Intestinal mucosal alterations in rats with carbon tetrachloride-induced cirrhosis: changes in glycosylation and luminal bacteria.
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. CCl4-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.
The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Sathish Kumar
SK
Natarajan
Prabhu
P
Ramamoorthy
Simmy
S
Thomas
Jayasree
J
Basivireddy
Gagandeep
G
Kang
Anup
A
Ramachandran
Anna B
AB
Pulimood
K A
KA
Balasubramanian
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001419:Bacteria / Q000302:isolation & purification*; D001422:Bacterial Adhesion; D050260:Carbohydrate Metabolism; D002251:Carbon Tetrachloride; D005260:Female; D006031:Glycosylation; D057927:Hydrophobic and Hydrophilic Interactions; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D017973:Tungsten Compounds / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000975:Antioxidants; D017973:Tungsten Compounds; D014810:Vitamin E; C025399:sodium tungstate(VI); D002251:Carbon Tetrachloride; D014969:Xanthine Oxidase