Evaluation of hepatic damage by reactive metabolites – administration with consideration of circadian variation of murine hepatic glutathione levels – was written by Mori, Koji;Kumano, Atsushi;Kodama, Toshihisa;Takiguchi, Shigeyuki;Takano, Naomi;Kumada, Kohei;Hatao, Kana;Kimura, Takashi. And the article was included in Journal of Toxicological Sciences in 2014.Electric Literature of C6H6N4 This article mentions the following:
Generally, reactive metabolites are detoxified by conjugation with glutathione (GSH). A GSH-depleted model was prepared by administering L-buthionine-(S,R)-sulfoximine (BSO), which can be used to detect hepatic damage by reactive metabolites. However, BSO may cause adverse effects on other organs, such as renal damage by reactive metabolites because it depletes GSH in the whole body. The present study was designed to examine whether it was possible to specifically detect hepatic damage by reactive metabolites without reducing renal GSH levels by administering BSO in a time course when hepatic GSH levels are naturally reduced. Male BALB/c mice were administered reverse osmosis (RO) water or 20 mmol/l BSO in drinking water for 4 days. Subsequently, animals in the RO water group were orally administered 500 mg/kg acetaminophen (APAP) at 9:00 or 15:00 and in the BSO group at 9:00 for 4 days. As a result, severe hepatic damage and necrosis of the renal proximal tubules were observed in the BSO/APAP administration at 9:00 group, and all animals died on 1 or 2 days after APAP administration. Hepatic damage was clearly increased in the RO water/APAP administration at 15:00 group compared with the RO water/APAP administration at 9:00 group. However, renal damage and deaths were not observed This BSO administration model may detect renal damage induced by reactive metabolites. Using an administration time course, whereby hepatic GSH levels were naturally reduced, hepatic damage by reactive metabolites can be detected without secondary renal effects. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Electric Literature of C6H6N4).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles are important five-member nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. 1,2,3-Triazoles are usually prepared following (3+2) cycloaddition protocols. A common technique for unsubstituted triazoles is the Huisgen azide-alkyne 1,3-dipolar cycloaddition: a azide and an alkyne react at high temperature to form a ring. However, the Huisgen strategy produces a mixture of isomers (typically 1,4- and 1,5-disubstituted) when used to produce substituted triazoles.Electric Literature of C6H6N4
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics