Lopez-Garcia, M. Pilar published the artcileKinetics of tienilic acid bioactivation and functional generation of drug-protein adducts in intact rat hepatocytes, Category: benzothiophene, the main research area is tienilic acid bioactivation protein adduct hepatocyte.
Drug-induced autoimmune hepatitis is among the most severe hepatic idiosyncratic adverse drug reactions. Considered multifactorial, the disease combines immunol. and metabolic aspects, the latter being to date much better known. As for many other model drugs, studies on tienilic acid (TA)-induced hepatitis have evidenced the existence of bioactivation during the hepatic oxidation of the drug, allowing the identification of the neoantigen of anti-LKM2 autoantibodies and the pathway responsible for its formation. However, most of these results are based on the use of microsomal fractions whose relevance to the liver in vivo still needs to be established. In the more complex intact cell environment, several endogenous processes may play a significant role on triggering the reaction and should therefore be considered. In this work the authors have characterized the kinetics of TA biotransformation in metabolically competent hepatocytes, the influence of TA bioactivation on physiol. GSH levels, and the qual. and quant. profile of drug-protein conjugates generated in situ, as a function of exposure time. Results confirm that intact hepatocytes reproduce in vitro the metabolic sequence that leads to the functional generation of drug-protein adducts, in conditions that simulate clin. human exposure to TA. Metabolically competent cultured hepatocytes appear as a very promising approach to investigate the early preimmunol. events of drug-induced autoimmune hepatitis, adequate to identify the conditions that may modulate the formation and specificity of drug-protein adducts in vivo, to study the hepatic disposition of the TA-protein targets, and to define the specific role of the hepatocyte in the origin of this adverse reaction.
Biochemical Pharmacology published new progress about Autoimmune hepatitis. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Category: benzothiophene.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem