The effect of acetaminophen on the structural and functional state of the large intestine and intestinal microflora

Objective. To assess the condition of the microbial-tissue complex of the large intestine when hepatotoxic concentrations of acetaminophen are administrated to the body of animals.Materials and methods. The experiments were performed on 24 white outbred rats weighing 180–220 g, which were divided into three groups. The control group received 2% starch solution enterally, the first experimental group was enterally administered with acetaminophen in starch solution at a dose of 1500 mg per kilogram of body weight, five times a day with one day interval; and the second experimental group was administered with acetaminophen at a dose of 2500 mg per kilogram of body weight the same way. Free amino acids and their nitrogen-containing metabolites were determined by high-performance liquid chromatography in samples of the microbial-tissue complex (MTC) of the large intestine previously frozen at -70 °C. For microbiological study, the aseptically isolated MTC was immediately sent to a microbiological laboratory for identification of the content of the main representatives of the intestinal microflora. Samples of the wall of the ascending colon were subjected to histological and electron microscopic examination. The hepatotoxic effect of acetaminophen was evaluated by registering the activity of enzymes and the content of total bilirubin in blood plasma.Results. Enteral administration of hepatotoxic amounts of acetaminophen to rats increases the concentrations of free amino acids and their nitrogen-containing derivatives in the microbial-tissue complex of the large intestine. At the same time, the concentrations of essential amino acids are significantly increased. Morphological changes in the cells of the epithelium of the large intestine and the structure of mitochondria have been shown.Conclusions. Toxic doses of acetaminophen have a significant impact on the indicators of the microbial-tissue complex of the large intestine. There are changes in biochemical parameters of amino acid metabolism: increased levels of substitutable amino acids and changes in the colonocytes (size and shape of mitochondria, the height of the brush border, the volume of the goblet cells), indicating decreased ability of the cells to use amino acids to support the functioning of the Krebs cycle. This is also confirmed by significantly increased concentrations of essential amino acids, which are mainly used for protein synthesis. The dysbiosis caused by acetaminophen further contributes to the damage to the large intestine. The negative effect of acetaminophen is confirmed by the dose-dependent changes we found in the microbial-tissue complex.