What is the mechanism of liver toxicity by acetaminophen?

What is the mechanism of liver toxicity by acetaminophen?

APAP hepatotoxicity is initiated by its conversion to the reactive intermediate NAPQI, which results in glutathione depletion and formation of APAP protein adducts. Adduct formation on mitochondrial proteins modulates respiratory chain function, producing elevated levels of free radicals such as superoxide.

What is the mechanism of acetaminophen toxicity?

Patients at Increased Risk. Because the mechanism of acetaminophen toxicity occurs via the formation of NAPQI, any factors that influence the availability of metabolic enzymes will therefore affect toxicity.

Which is the correct pathogenesis of acetaminophen induced liver injury?

Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury.

Is ibuprofen safe for liver?

Nonprescription pain relievers such as acetaminophen (Tylenol, others), aspirin, ibuprofen (Advil, Motrin IB, others) and naproxen (Aleve, others) can damage your liver, especially if taken frequently or combined with alcohol.

What is APAP level?

The acetaminophen drug level is a blood test used to screen for the presence of the common pain reliever acetaminophen. This over-the-counter (OTC) medicine is used to treat pain and reduce fever.

What is the toxic metabolite of acetaminophen?

Acetaminophen is a widely used over-the-counter drug that causes severe hepatic damage upon overdose. Cytochrome P450-dependent oxidation of acetaminophen results in the formation of the toxic N-acetyl-p-benzoquinone-imine (NAPQI).

Is paracetamol same as acetaminophen?

Acetaminophen is the United States adopted name,4 and in the United States the substance is always and only called acetaminophen. Paracetamol is the recommended international non-proprietary name,4 the British approved name,4 and the name used for the substance throughout the world outside the United States.

Is paracetamol safe in liver disease?

Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage.

How is APAP metabolized in the human body?

The remaining APAP, approximately 5–9% is metabolized by the cytochrome P450 enzymes (CYPs), mainly CYP 2E1 into the highly reactive intermediate metabolite N-acetyl-p-benzoquinone imine (NAPQI) [66]. Generally, NAPQI is rapidly detoxified by conjugating with glutathione (GSH).

How are lipid peroxides elevated by Apap?

Using mass spectrometry, we found that lipid peroxides derived from n-6 fatty acids, mainly arachidonic acid, were elevated by APAP, and that auto-oxidation is the predominant mechanism of APAP-derived lipid oxidation.

Which is the best antioxidant for APAP overdose?

As such, the United States Food and Drug Administration recommends N-acetyl cysteine (NAC), a known antioxidant, as the only therapeutic option for APAP-overdosed patients; however, this medication has its limitations including adverse effects and narrow therapeutic window [31].

Which is the best stage of APAP detoxification?

In another word, the regulation of APAP detoxification at the phase II level is beneficial in alleviating APAP hepatotoxicity.