Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury

Table 1 Factors influencing N-acetyl-p-benzoquinone imine production

Factor	Description	Ref.
CYP enzyme activity	CYP2E1, CYP1A2, and CYP3A4 are responsible for metabolizing APAP to NAPQI. Among these, CYP2E1 plays a predominant role and can be upregulated	[12]
Chronic alcohol consumption	Alcohol use results in induction of CYP2E1 and depletion of GSH, thereby raising NAPQI formation and diminishing detoxification capacity	[11]
Concomitant drug use	Drugs that induce CYP enzymes (e.g., phenobarbital) can increase the production of NAPQI	[13]
Genetic polymorphisms	Genetic polymorphisms in CYP genes can alter enzyme activity, influencing NAPQI formation	[14]
GSH levels	GSH conjugates NAPQI to facilitate detoxification. Insufficient GSH leads to the accumulation of NAPQI and subsequent toxicity	[10]
Fasting/malnutrition	Fasting depletes GSH reserves, thereby increasing susceptibility to NAPQI toxicity	[15]
Pre-existing liver disease	Pre-existing liver disease may modify CYP enzyme function and decrease GSH synthesis, resulting in impaired NAPQI elimination	[16]

CYP: Cytochrome P450; APAP: N-acetyl-p-aminophenol (Acetaminophen); NAPQI: N-acetyl-p-benzoquinone imine; GSH: Glutathione.