A cytochrome P450-independent mechanism of acetaminophen-induced injury in cultured mouse hepatocytes was written by Miyakawa, Kazuhisa;Albee, Ryan;Letzig, Lynda G.;Lehner, Andreas F.;Scott, Michael A.;Buchweitz, John P.;James, Laura P.;Ganey, Patricia E.;Roth, Robert A.. And the article was included in Journal of Pharmacology and Experimental Therapeutics in 2015.Recommanded Product: 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:
Mouse hepatic parenchymal cells (HPCs) have become the most frequently used in vitro model to study mechanisms of acetaminophen (APAP)-induced hepatotoxicity. It is universally accepted that APAP hepatocellular injury requires bioactivation by cytochromes P 450 (P450s), but this remains unproven in primary mouse HPCs in vitro, especially over the wide range of concentrations that have been employed in published reports. The aim of this work was to test the hypothesis that APAP-induced hepatocellular death in vitro depends solely on P450s. We evaluated APAP cytotoxicity and APAP-protein adducts (a biomarker of metabolic bioactivation by P 450) using primary mouse HPCs in the presence and absence of a broad-spectrum inhibitor of P450s, 1-aminobenzotriazole (1-ABT). 1-ABT abolished formation of APAP-protein adducts at all concentrations of APAP (0-14 mM), but eliminated cytotoxicity only at small concentrations (≤5 mM), indicating the presence of a P 450-independent mechanism at larger APAP concentrations P 450-independent cell death was delayed in onset relative to toxicity observed at smaller concentrations p-Aminophenol was detected in primary mouse HPCs exposed to large concentrations of APAP, and a deacetylase inhibitor [bis (4-nitrophenyl) phosphate (BNPP)] significantly reduced cytotoxicity. In conclusion, APAP hepatocellular injury in vitro occurs by at least two mechanisms, a P 450-dependent mechanism that operates at concentrations of APAP ≤ 5 mM and a P 450-independent mechanism that predominates at larger concentrations and is slower in onset. P-Aminophenol most likely contributes to the latter mechanism. These findings should be considered in interpreting results from APAP cytotoxicity studies in vitro and in selecting APAP concentrations for use in such studies. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Recommanded Product: 1H-Benzo[d][1,2,3]triazol-1-amine).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The many free lone pairs in triazoles make them useful as coordination compounds, although not typically as haptic ligands. Triazole growth retardants such as uniconazole and paclobutrazol have been known to inhibit the biosynthesis of gibberellins by blocking kaurene oxidase, an P450 enzymeRecommanded Product: 1H-Benzo[d][1,2,3]triazol-1-amine
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics