Alcohol as a risk factor for drug-induced diseases

Administration of a rational and safe drug therapy is one of the most challenging issues for healthcare professionals. The frequency of hospitalizations due to the adverse drug reactions in the years 2000 — 2015 was estimated at 6.3 (3.3—11.0 %) for developed countries and 5.5 % (1.1—16.9 %) for developing countries. It is known that alcohol intake is a risk factor for many socially significant diseases, including arterial hypertension, coronary heart disease, chronic heart failure, etc., however, many doctors pay insufficient attention to the fact that many drugs, for example, beta-blockers, antidepressants, bezodisepines, calcium antagonists, can interact with alcohol when consumed simultaneously and, thus, increase the risks of adverse drug reactions. There are 2 main types of interactions between alcohol and drugs: pharmacokinetic (at the stage of absorption, distribution, metabolism and elimination) and pharmacodynamic (at the stage of effects and receptors). For example: the simultaneous intake of alcohol and paracetamol leads to the formation of toxic metabolites due to the induction of cytochrome P450 isoenzymes by alcohol. Another example is decrease in presystemic elimination and stimulation of the metabolism of tricyclic antidepressants; an increase in the elimination of imipramine and desipramine in patients with chronic alcoholism after detoxification therapy, and so on. In this article, the authors analyzed and systematized data from open literature sources in order to inform health care professionals about the possible risks associated with the interaction of alcohol and drugs and various pharmacological groups.

Identification and localization of soluble sulfotransferases in the human gastrointestinal tract

Soluble SULTs (sulfotransferases) are important in the regulation of messenger molecules and the elimination of xenobiotics. However, sulfo-conjugation of various substrates can also lead to the formation of reactive metabolites that may induce cancer and cause other damage. The aim of the present study was to identify the SULT forms expressed in the human gastrointestinal tract, especially the colon and rectum (common sites for cancer), and to determine their cellular localization. Normal colonic or rectal tissue, resected with tumours, was obtained from 39 subjects. For comparison, we additionally studied one to four samples from stomach, jejunum, ileum, cecum and liver. SULTs were detected by immunoblotting, immunohistochemistry and measurement of enzyme activities. SULT1A1, 1A3 and 1B1 were found in all parts of the gastrointestinal tract, often exceeding levels in liver (where these forms were present at high, undetectable and low levels respectively). They were predominantly localized in differentiated enterocytes. SULT1E1 and 2A1 were only detected in liver, jejunum, ileum and cecum. SULT1C1 was readily found in stomach, but was negligible elsewhere. SULT1A2 was present at low levels in individual samples. The remaining forms were not detected with the limitation that only high levels could be recognized with the antisera used. In conclusion, SULTs are abundant in the gastrointestinal tract of man. We suspect that they are involved in the presystemic elimination of bioactive food-borne components, including aglycones released by gut microbiota, as well as the bioactivation of some procarcinogens.