Investigation of Intestinal Absorption and Excretion of Paracetamol in Streptozotocin-Induced Hyperglycemia

Abstract

The phenolic drug molecules can be metabolized, among others, by the small intestine’s enterocytes. The conjugation reactions (glucuronidation and sulfation) show great importance in these transformations, although the oxidation reactions can be significant. These processes are dependent on the substituents of the phenolic compounds or the reacting functional groups (hydroxyl or carboxyl). Pathologic conditions, e.g., permanent hyperglycemia and diabetes, can alter the activities of the conjugative and possibly the oxidative enzymes, thus forming a change in the metabolic pattern and eventually provoking oxidative stress. A rat intestinal perfusion model was used to investigate the way in which experimental hyperglycemia affects the paracetamol’s intestinal elimination and metabolism. Hyperglycemia was induced by the administration of streptozotocin. Two hundred and fifty µM paracetamol was used in the intestinal perfusion solution. For the quantitation of the paracetamol and its major metabolites in the intestinal perfusate, an isocratic high-performance liquid chromatography method with UV-Vis detection was developed. The results revealed that quantities of all of the measured metabolites (glucuronide, sulfate, cysteine, and mercapturic acid conjugates) increased as the effect of the streptozotocin-induced hyperglycemia also did. In the small intestine’s homogenate, the glutathione levels showed that there was a decrease in the hyperglycemia levels after the paracetamol administration. In contrast, the tissue levels of the cysteine were lower in the streptozotocin-induced hyperglycemia and increased after the administration of the paracetamol. The changes in the activity of the intestinal CYP 3A4, CYP 2E1, and cyclooxygenase (COX) enzymes were determined in the control and the hyperglycemic cases. Still, there was a significant observable enzyme activity elevation in the intestinal COX enzymes, but there was a decrease in the amount of activity of the intestinal CYP3A4 enzymes, and the CYP2E1 enzyme activity was practically changeless. The results on the cysteine levels in the intestinal homogenate, at least partly, can be explained by the regulation function of the cysteine during the occurrence of oxidative stress.

Valorization and Upcycling of Acid Mine Drainage and Plastic Waste via the Preparation of Magnetic Sorbents for Adsorption of Emerging Contaminants

“…This suggests that the surface of the material was positively charged for MMC and negative for MMAC-25% and MMAC-50%. The analytes had p K a values of 9.51, 14.0, and 13.9 for ACT, CAF, and CBZ, meaning that at this pH range, the analytes are in their molecular state. − This translates to the presence of the lone pairs on the analytes to be available for ionic interaction with the positively charged MMC. For the MMAC-25% and MMAC-50%, the mechanism of adsorption is suggested to include pore filling and π–π interactions …”

Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections

“…For instance, hyperglycemia strongly induces the CYP2E1 mitochondrial isoform [166]. A few other CYP isoenzymes have been found to be stimulated in diabetic patients, either altering the catabolism of CYP-substrate drugs (i.e., paracetamol [167] or the synthetic pathways of bioactive molecules needed for regulating physiological process [168,169].…”