Abstract
BackgroundPrevious results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I). The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with advanced cirrhosis and ascites. Thus, jejunal structure and nutrient transport (D-galactose, L-leucine, L-proline, L-glutamic acid and L-cystine) were studied in rats with ascitic cirrhosis.MethodsAdvanced cirrhosis was induced by CCl4 inhalation and Phenobarbital administration for 30 weeks. Cirrhotic animals were divided into two groups which received IGF-I or saline during two weeks. Control group was studied in parallel. Jejunal microvilli were studied by electron microscopy. Nutrient transport was assessed in brush border membrane vesicles using 14C or 35S-labelled subtracts in the three experimental groups.ResultsIntestinal active Na+-dependent transport was significantly reduced in untreated cirrhotic rats. Kinetic studies showed a decreased Vmax and a reduced affinity for sugar and four amino acids transporters (expressed as an increased Kt) in the brush border membrane vesicles from untreated cirrhotic rats as compared with controls. Both parameters were normalised in the IGF-I-treated cirrhotic group. Electron microscopy showed elongation and fusion of microvilli with degenerative membrane lesions and/or notable atrophy.ConclusionsThe initial microvilli elongation reported in non ascitic cirrhosis develops into atrophy in rats with advanced cirrhosis and nutrient transports (monosaccharides and amino acids) are progressively reduced. Both morphological and functional alterations improved significantly with low doses of IGF-I.
Highlights
Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli
The transport of galactose, L-leucine, L-proline (IMINO acid), L-glutamic acid and L-cystine- were investigated in brush border membrane vesicles (BBMV) in control rats, in untreated cirrhotic rats and in cirrhotic rats treated with Insulin-Like Growth Factor-I (IGF-I)
In the presence of sodium gradient, untreated cirrhotic animals had a significant lower uptake as compared to controls, whereas BBMV from IGF-I-treated cirrhotic group presented normal values not significantly different compared to controls and significantly higher than those of BBMV from untreated cirrhotic rats
Summary
Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. Recently published results have shown that in rats with non-ascitic cirrhosis there is an alteration of sugars and amino acid transport associated with elongation of microvilli [13,15,16] Both morphological and functional alterations returned to normal with the administration of IGFI, at low doses [13,15,16]. The specific aims of this study were: 1) to investigate the structure of jejunal microvilli and intestinal function in rats with ascitic liver cirrhosis; and 2) to study whether IGF-I could influence intestinal disturbances in advanced stages of the hepatic disease For these purposes, the transport of galactose, L-leucine (neutral amino acid), L-proline (IMINO acid), L-glutamic acid (anionic or acidic amino acid) and L-cystine (sulfurate amino acid)- were investigated in brush border membrane vesicles (BBMV) in control rats, in untreated cirrhotic rats and in cirrhotic rats treated with IGF-I. Electron microscopy (EM) of jejunal mucosa was performed in the three experimental groups
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