Intestinal Absorption and Transformation of the Increased Dose of Paracetamol in Streptozotocin-Induced Diabetic Rats

Background: Luminal disappearance of the paracetamol and the appearance of its metabolites (paracetamol-beta-D-glucuronide (PG), paracetamol sulfate (PS), paracetamol cysteine (PC) and paracetamol mercapturate (PM)) were investigated in control and in experimental diabetic rats of the perfused paracetamol substrate. Methods: Experimental diabetes was induced by the administration of streptozotocin (STZ) (65 mg/kg, intravenous (IV)). The paracetamol solution was luminally perfused through the small intestine of anesthetized rats, and the parent compound and its metabolites were determined from the perfusion solution with an isocratic reverse phased high performance liquid chromatography (RP-HPLC) method. Results: The excreted amount of paracetamol metabolites increased after the STZ pretreatment, and the concentration of the glutathione (GSH) in the small intestine tissue homogenate showed a decreasing tendency, although the perfused paracetamol does not accelerate the observed changing tendency. The oxidative stress caused by the STZ contributed to the formation of the oxidized glutathione (GSSG), and its level was elevated by the effect of the paracetamol administration. The paracetamol administration alone did not provoke the detectable appearance of the GSSG. Conclusions: The elevated paracetamol concentration and the experimental diabetes negatively influenced the absorption of the paracetamol. The protective GSH level showed a decreasing tendency, while the level of the oxidative stress indicator GSSG was higher.