It is used to protect hepatic GSH during detoxification of NAPQI
In an overdose, a large amount of NAPQI
is generated causing depletion of glutathione stores which overwhelms the detoxification process and leads to liver cell damage.
AAN is caused by accumulation of a toxic metabolite, NAPQI
It has been reported that the toxic metabolite of acetaminophen bound covalently to cell macromolecules; NAPQI
, the toxic metabolite of acetaminophen was reported to be metabolised by cytochrome P-450 in liver and subsequently detoxified.
Tan pretreatment might have enhanced HO-1 expression prior to APAP exposure, contributing to the detoxification process of the reactive intermediate NAPQI
, thereby protecting against liver injury (Reisman et al.
The metabolic activation of APAP to NAPQI
is catalyzed by a variety of cytochrome P450 isoforms including CYP2E1, CYP3A4, and CYP1A2 (Hinson et al.
At therapeutic doses, about 90% of APAP is eliminated via sulfation or glucuronidation pathways [32, 33] and another 5% is metabolized by cytochrome P450 2E1 (CYP2E1) to NAPQI
Preventive antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) are involved in direct elimination of reactive oxygen species, namely, superoxide radical and hydrogen peroxide that emanated from the disruptive effect of NAPQI
En una intoxicacion con acetaminofen, su catabolismo principal por la fase II cambia a la fase I produciendo el radical NAPQI
, que ocasiona danos en la arquitectura celular; al agotar la reserva de GSH y por la propagacion de las EROS que no llegan a ser neutralizadas por los mecanismos antioxidantes, se establece una situacion de estres oxidativo y dano hepatocelular.
is an electrophilic intermediate which is oxidized by cytochrome P450 and converted to a highly reactive and toxic metabolite as in the case of paracetamol overdose (Dahlin et al.
is usually reduced to a nontoxic mercaptate conjugate by glutathione.
Paracetamol warfarin interaction: NAPQI
, the toxic metabolite of paracetamol, is an inhibitor of enzymes in the vitamin K cycle.