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PubMed2004

Histological picture of intestinal mucosa of rats after simultaneous administration of atorvastatin and ethyl alcohol.

The rats received atorvastatin in the therapeutical dose and 10x higher, 20% solution of ethanol and ethanol with atorvastatin for 6 weeks. The microscopic investigations (H + E staining, Masson's method, PAS method by McManus) showed no changes in histological picture of intestinal mucosa after giving atorvastatin. The rats receiving alcohol and alcohol with atorvastatin showed similar changes, but different than the first groups. Under the epithelium of intestinal villi there were observed light, vesicle-like spaces, separation of epithelium from connective tissue stroma, also lack of the epithelium of the top of villi and hyperaemia of stroma of villi. The observed changes were stronger in rats receiving simultaneously alcohol and atorvastatin in the dose 10x higher than therapeutical. Hyperaemia of connective tissue of stroma of villi was still visible after month period of administration.

Animals↗
PubMed1991

Long-term effects of an inotropic phosphodiesterase inhibitor (ICI 153,110) on the rat salivary gland, harderian gland, and intestinal mucosa.

The inotropic vasodilator, ICI 153,110, a phosphodiesterase inhibitor intended for the treatment of congestive heart failure, was administered to Alderley Park Wistar-derived rats for periods of up to 182 days. Treatment produced hypertrophy of salivary glands, hyperplasia of intestinal mucosa, and dacryoadenitis of the harderian gland. As the functions of these glandular tissues can be modified by factors which alter cyclic nucleotide metabolism, it is postulated that the glandular alterations produced by ICI 153,110 occurred as a result of phosphodiesterase inhibition.

Animals↗
PubMed1987

On the mechanism of action of bovine intestinal mucosa 5'-nucleotide phosphodiesterase. Stereochemical evidence for a nucleotidyl-enzyme intermediate.

The diastereoisomers of adenosine 5'-O-phosphorothioate O-methyl ester have been synthesised. Only the Sp diastereoisomer is a substrate for the 5'-nucleotide phosphodiesterase from bovine intestinal mucosa. The previously unidentified enantiomer of 4-nitrophenyl phenyl phosphonothioate hydrolysed by the enzyme is shown to have the Sp configuration. Digestion of the Sp diastereoisomer of adenosine 5'-O-phosphorothioate O-methyl ester by the enzyme in 18O-labelled water gave 18O-labelled adenosine 5'-O-phosphorothioate which was stereochemically analysed by methylation and subsequent 31P-NMR spectroscopy and shown to possess the Sp configuration. Thus the enzyme-catalysed cleavage proceeded with retention of configuration at phosphorus, presumably via a double-displacement mechanism. This provides strong evidence for the existence of a nucleotidyl-enzyme intermediate on the reaction pathway.

Adenosine Monophosphate↗
PubMed1988

The effects of orally administered linoleic acid and its autoxidation products on intestinal mucosa in rat.

Linoleic acid and its autoxidation products, hydroperoxides and their secondary products, were orally administered to rats (350 mg each/rat). Hemorrhage was seen in the alimentary canal at 6 h after the dose of hydroperoxides. To examine their toxicities on intestinal mucosa, the activities of mucous enzymes (sucrase, maltase, and alkaline phosphatase) were measured. Hydroperoxides and their secondary products decreased the enzyme activities in jejunum at 6 h after the doses and increased them in both jejunum and ileum at 15 h, as compared to linoleic acid or saline solution. The decrease of enzyme activity was marked in the hydroperoxide group and the increase was marked in the secondary product group. Then, in in vitro experiments, the effects of autoxidation products on these enzymes were determined. Autoxidation products inactivated only alkaline phosphatase. Thus, the results in vivo disagreed with those in vitro. It was assumed that autoxidation products orally administered attacked a membrane of intestinal microvilli whereas in vitro they directly affected the enzymes.

Administration, Oral↗