The Relative Importance of the Small Intestine and the Liver in Phase II Metabolic Transformations and Elimination of p-Nitrophenol Administered in Different Doses in the Rat

Abstract

Intestinal and hepatic function have been investigated in phase II metabolic reactions and elimination of p-nitrophenol (PNP) in the rat. A jejunal loop was cannulated and recirculated with isotonic solutions containing PNP in different concentrations (0, 20, 100, 500, 1000 µM). Samples were obtained from the perfusate at given intervals. To investigate the metabolic and excretory functions of the liver, the bile duct was cannulated, and the bile was collected. Metabolites of PNP were determined by validated HPLC (high pressure liquid chromatography) methods. The results demonstrated the relative importance of the small intestine and the liver in phase II metabolic transformations and elimination of PNP. There were significant differences between the luminal and biliary appearances of p-nitrophenol-glucuronide (PNP-G) and p-nitrophenol–sulfate (PNP-S). The PNP-G appeared in the intestinal lumen at the lower PNP concentrations (20 µM and 100 µM) at higher rate than in the bile. No significant difference was found between the intestinal and the biliary excretion of PNP-G when PNP was administered at a concentration of 500 µM. However, a reverse ratio of these parameters was observed at the administration of 1000 µM PNP. The results indicated that both the small intestine and the liver might play an important role in phase II metabolic reactions and elimination of PNP. However, the relative importance of the small intestine and the liver can be dependent on the dose of drugs.

Investigation of the factors responsible for the low oral bioavailability of alizarin using a sensitive LC‐MS/MS method: In vitro, in situ, and in vivo evaluations

“…Furthermore, the results depicted in Figure 6 show that the intestine and liver have significant metabolic activity for alizarin. This result is supported by the fact that several UDPglucuronosyltransferase and sulfotransferase isoforms are expressed in the rat and human gut tracts (Almási et al, 2020;Mizuma, 2009).…”

“…Furthermore, the results depicted in Figure 6 show that the intestine and liver have significant metabolic activity for alizarin. This result is supported by the fact that several UDP‐glucuronosyltransferase and sulfotransferase isoforms are expressed in the rat and human gut tracts (Almási et al, 2020; Mizuma, 2009). Notably, the hepatic CL int,S9 was significantly higher than the intestinal CL int,S9 in rat S9 fractions, while they were comparable to each other in human S9 fractions; the intestinal CL int,S9 was approximately 10‐fold higher in HIS9 than that in RIS9.…”

Effect of experimental hyperglycemia on intestinal elimination and biliary excretion of ibuprofen enantiomers in hyperglycemic rats

“…The experiments were performed according to the protocol before [8][9][10]. The animals fasted for 18-20 h before the experiments; and then were anesthetized with an intraperitoneal injection of urethane (1.2 g/kg bw, i.p.).…”

Electrochemical Detection of 4‐Nitrophenol Using A Screen‐Printed Carbon Electrode Modified by Rod‐Shaped Nickel Oxide Nanoparticles

“…In recent years, researchers have used many analytical methods to detect 4‐NP, including spectrophotometric determination, [6] high‐performance liquid chromatography (HPLC), [7] fluorescent detection, [8] capillary electrophoresis microchips, [9] flow immunoassay with fluorescence, [10] gas chromatography with mass spectrum, [11] and electrochemical method [1] . However, these conventional techniques require costly reagents, trained personnel, and expensive equipment, and they are susceptible to interference from related chemicals.…”