MEHP/ethanol co-exposure favors the death of steatotic hepatocytes, possibly through CYP4A and ADH involvement was written by Tete, Arnaud;Gallais, Isabelle;Imran, Muhammad;Legoff, Louis;Martin-Chouly, Corinne;Sparfel, Lydie;Bescher, Maelle;Sergent, Odile;Podechard, Normand;Lagadic-Gossmann, Dominique. And the article was included in Food and Chemical Toxicology in 2020.Electric Literature of C16H19BrN2OS The following contents are mentioned in the article:
Liver steatosis has been associated with various etiol. factors (obesity, alc., environmental contaminants). How those factors work together to induce steatosis progression is still scarcely evaluated. Here, we tested whether phthalates could potentiate death of steatotic hepatocytes when combined with ethanol. Pre-steatotic WIF-B9 hepatocytes were co-exposed to mono (2-ethylhexyl) (MEHP, 500 nM; main metabolite of di (2-ethylhexyl) phthalate or DEHP) and ethanol (5 mM) for 5 days. An increased apoptotic death was detected, involving a DNA damage response. Using 4-Methypyrazole to inhibit ethanol metabolism, and CH-223191 to antagonize the AhR receptor, we found that an AhR-dependent increase in alc. dehydrogenase (ADH) activity was essential for cell death upon MEHP/ethanol co-exposure. Toxicity was also prevented by HET0016 to inhibit the cytochrome P 450 4A (CYP4A). Using the antioxidant thiourea, a role for oxidative stress was uncovered, notably triggering DNA damage. Finally, co-exposing the in vivo steatosis model of high fat diet (HFD)-zebrafish larvae to DEHP (2.56 nM)/ethanol (43 mM), induced the pathol. progression of liver steatosis alongside an increased Cyp4t8 (human CYP4A homolog) mRNA expression. Altogether, these results further emphasized the deleterious impact of co-exposures to ethanol/environmental pollutant towards steatosis pathol. progression, and unraveled a key role for ADH and CYP4A in such effects. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Electric Literature of C16H19BrN2OS).
2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.Electric Literature of C16H19BrN2OS
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica