Co‐administration of N‐Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity

Abstract

Preclinical Research Although acetaminophen (APAP) is an effective analgesic and anti-pyretic, APAP overdose is the most frequent cause of serious, often lethal, drug-induced hepatotoxicity. Administration of N-acetyl cysteine (NAC) within 8 hours of APAP overdose effectively mitigates APAP-induced hepatotoxicity. Thus, preventing APAP toxicity before it occurs by formulating APAP with NAC is logical and, as we show here in a mouse model, is effective in preventing APAP toxicity. Thus, toxic oral APAP doses sufficient to cause severe widespread liver damage do not cause significant damage when administered concurrently with equal amounts of NAC, that is, in the NAC-APAP treated animals, hepatic transaminases increase only marginally and liver architecture remains fully intact. Thus, we conclude that concomitant oral dosing with APAP and NAC can provide a convenient and effective way of preventing toxicity associated with large dosage of APAP. From a public health perspective, these findings support the concept that a co-formulation of APAP plus NAC is a viable over-the-counter (OTC) alternative to the current practice of providing APAP OTC and treating APAP toxicity if/when it occurs. In essence, our findings indicate that replacing the current OTC APAP with a safe and functional APAP/NAC formulation could prevent the accidental and intentional APAP toxicity that occurs today.

Hepatotoxicity due to zinc phosphide poisoning in two patients: role of N‐acetylcysteine

“…Till date, only few studies have reported this fact. However, NAC has been demonstrated as a potential antidote for the treatment of thinner and acetaminophen-intoxicated patients or as nephroprotective agent to attenuate chemical or biochemical and electrolytes imbalance [21][22][23].…”

Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats

“…On the ninth day, 24 h post last toxic APAP dose, [17,18,19] all rats were euthanized by cervical dislocation, and blood samples were withdrawn by cardiac puncture, collected in sterile plain centrifugation tubes and left at room temperature for 15 min to clot completely. After that, serum was obtained by centrifugation at 6000 rpm for 10 min at room temperature and kept at −20 °C until further testing.…”

Impact of medication on protein and amino acid metabolism in the elderly: the sulfur amino acid and paracetamol case

“…N -acetylcysteine is a drug that replenishes GSH stores in vivo ( 98 ) . Co-administration of APAP and N -acetylcysteine could prevent acute APAP toxicity, as has been shown in a preclinical study ( 99 ) .…”