Effect of Diethylether on the Formation of Paracetamol Sulphate and Glucuronide in Isolated Rat Hepatocytes

Abstract

Diethylether has previously been shown to inhibit several pathways of drug metabolism, including conjugation of paracetamol in isolated rat hepatocytes. Since overall paracetamol conjugation consists of pathways of different subcellular localization (cytosolar sulphation and microsomal glucuronidation) the response of both pathways to diethylether was tested. The elimination of paracetamol (160 µmol/l, initial concentration) and the formation of paracetamol sulphate and glucuronide were measured (high-performance liquid chromatography) in suspensions of isolated rat hepatocytes from fasted and fed animals over 1 h in the absence and presence of diethylether (30 mmol/l). Approximately 90% of the paracetamol elimination was by sulphation and nearly 10% by glucuronidation both in the controls and in the presence of ether. The overall disposition of paracetamol and the formation of sulphate were both reduced by about 50% in the presence of ether compared to the controls while the formation of glucuronide was reduced by 70%. The results were not influenced by the nutritional state of the animals before sacrifice. It is concluded that the inhibitory effect of ether on total paracetamol metabolism was mainly caused by reduced sulphation. Since microsomal glucuronidation was also inhibited by ether, both cytosolar and microsomal enzyme systems were sensitive to diethylether.

The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches

“… 48 Blood was left for 10 min to clot and centrifuged at 3000 rpm (1.1750 × g ) to obtain serum. 48 The separated serum was stored at −80 °C for biochemical analysis.…”

“…At the end of the experiment, the rats were fasted overnight, subjected to anesthesia and sacrificed. 48 The whole brain of each rat was rapidly dissected, washed with isotonic saline and dried on filter paper. The brain was weighed and homogenized in ice-cold medium containing 50 mM Tris/HCl and 300 mM sucrose at pH 7.4 to give a 10% (w/v) homogenate.…”

Influence of Advanced Age on the Formation and Elimination of Acetaminophen Metabolites by Male Rats

“…Sur gery and anesthesia lasted approximately 20 min and all procedures were completed in the morning to min imize the known influence of diethyl ether on the elimination of acetaminophen [15,16). Animals were housed overnight in individual plastic metabolism cages with access to water and food.…”

In situ liver perfusion techniques: the significance of the anaesthetic procedure used

“…Diethylether does certainly influence the hepatic drug metabolism system, since it is about 10% metabolised itself (18) and is known to inhibit various oxidative routes of drug metabolism (19), including hydroxylation of phenytoin (20). It also depletes intrahepatic UDP glucuronic acid concentrations (13) and thus decreases glucuronidation of some substrates (12,21). However, such interactions are unlikely to be of relevance in the present study, because the initial hepatic concentration of ether should be very much lower than those in the studies refered to above, most of which involved the use of continuous ether anaesthesia.…”