Retinoid metabolism in the small intestine during development of liver cirrhosis.
OBJECTIVE
Retinoids are important mediators of cellular differentiation and proliferation in various epithelia of the body including the small intestine. Though alterations in intestinal epithelial cell proliferation have been noted in liver cirrhosis, mechanisms involved in the process are not well understood. This study examined the levels of various retinoids and retinoid-metabolizing enzymes in the small intestine during development of liver cirrhosis.


METHODS
Four groups of animals were used (control, phenobarbitone control, thioacetamide and carbon tetrachloride treatment). Twice-weekly intragastric or i.p. administration of carbon tetrachloride or thioacetamide, respectively, produced liver cirrhosis after 3 months, which was confirmed through histology and serum markers. Retinoid levels were measured by high-performance liquid chromatography.


RESULTS
A decrease in the levels of retinal, retinoic acid and retinol was evident in the intestine by 3 months, when cirrhosis was evident histologically, and these remained low until 6 months. A decrease in the activities of retinaldehyde oxidase, retinaldehyde reductase and retinol dehydrogenase was also seen in intestine from cirrhotic rats.


CONCLUSIONS
These results suggest that altered retinoid metabolism in the intestine of cirrhotic rats might have an influence on changes in intestinal epithelial cell differentiation, seen in liver cirrhosis.
Natarajan
Sathish Kumar
SK
The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Amirtharaj
G Jayakumar
GJ
Ramachandran
Anup
A
Pulimood
Anna B
AB
Balasubramanian
Kunissery A
KA
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D015536:Down-Regulation; D020895:Enterocytes / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D012172:Retinaldehyde / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D013853:Thioacetamide; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
D015415:Biomarkers; D012176:Retinoids; D013853:Thioacetamide; D014801:Vitamin A; D014212:Tretinoin; D002251:Carbon Tetrachloride; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase; D012172:Retinaldehyde