Nishiya, Takayoshi published the artcileThe crucial protective role of glutathione against tienilic acid hepatotoxicity in rats, Application In Synthesis of 40180-04-9, the main research area is glutathione tienilic acid hepatotoxicity.
To investigate the hepatotoxic potential of tienilic acid in vivo, the authors administered a single oral dose of tienilic acid to Sprague-Dawley rats and performed general clinicopathol. examinations and hepatic gene expression anal. using Affymetrix microarrays. No change in the serum transaminases was noted at up to 1000 mg/kg, although slight elevation of the serum bile acid and bilirubin, and very mild hepatotoxic changes in morphol. were observed In contrast to the marginal clinicopathol. changes, marked upregulation of the genes involved in glutathione biosynthesis [glutathione synthetase and glutamate-cysteine ligase (Gcl)], oxidative stress response [heme oxygenase-1 and NAD(P)H dehydrogenase quinone 1], and phase II drug metabolism (glutathione S-transferase and UDP glycosyltransferase 1A6) were noted after 3 or 6 h postdosing. The hepatic reduced glutathione level decreased at 3-6 h, and then increased at 24 or 48 h, indicating that the upregulation of NF-E2-related factor 2 (Nrf2)-regulated gene and the late increase in hepatic glutathione are protective responses against the oxidative and(or) electrophilic stresses caused by tienilic acid. In a subsequent experiment, tienilic acid in combination with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of Gcl, caused marked elevation of serum alanine aminotransferase (ALT) with extensive centrilobular hepatocyte necrosis, whereas BSO alone showed no hepatotoxicity. The elevation of ALT by this combination was observed at the same dose levels of tienilic acid as the upregulation of the Nrf2-regulated genes by tienilic acid alone. Apparently, the impairment of glutathione biosynthesis may play a critical role in the development of tienilic acid hepatotoxicity through extensive oxidative and(or) electrophilic stresses.
Toxicology and Applied Pharmacology published new progress about Bile acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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, Application In Synthesis of 40180-04-9.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem