Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity

Zillen, Daan; Movig, Kris L. L.; Kant, Gert; Masselink, Joost B.; Mian, Paola

doi:10.1002/ccr3.4611

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…When APAP is consumed orally, it is absorbed into the duodenum via passive diffusion [16,17] . APAP will move from the intestinal tract lumen across a mucosal membrane into the bloodstream by either direct diffusion through epithelial and endothelial cells or paracellular transport [18,19] . The primary location of absorption is the small intestine through the so-called "absorption window" of the duodenum and jejunum, although small (almost negligible) amounts of APAP are absorbed by the stomach [16] .…”

Section: Apap Absorption In the Duodenummentioning

confidence: 99%

Fructose as a novel nutraceutical for acetaminophen (APAP)-induced hepatotoxicity

Rodrigues,

Hussain,

Cooke

et al. 2023

Metab Target Organ Damage

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Acetaminophen (APAP) is the most widely used analgesic in the world. APAP overdose can cause severe hepatotoxicity and therefore is the most common cause of drug-induced liver injury. The only approved treatment for APAP overdose is N-acetyl-cysteine (NAC) supplementation. However, the narrow efficacy window of the drug severely limits its clinical use, prompting the search for other therapeutic options to counteract APAP toxicity. Recent research has pointed to fructose as a novel nutraceutical for APAP-induced liver injury. This review summarizes the current understanding of the molecular mechanisms underlying APAP-induced liver injury, introduces how fructose supplementation could prevent and treat APAP liver toxicity with a focus on the ChREBPα-FGF21 pathway, and proposes possible future directions of study.

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Section: Apap Absorption In the Duodenummentioning

confidence: 99%

Fructose as a novel nutraceutical for acetaminophen (APAP)-induced hepatotoxicity

Rodrigues,

Hussain,

Cooke

et al. 2023

Metab Target Organ Damage

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“…Acetaminophen (APAP) is one of the most popular and widely used analgesic and antipyretic drugs globally [1,2], and it is included in the WHO model list of essential medicines [3]. Although this chemical is safe for most individuals, there is a risk of developing drug-induced liver injury (DILI) in some patients with pre-existing pathological conditions such as liver damage [4], malnutrition [5,6], co-medication [7], age [8], genetics [9], or tobacco consumption [10], among others [1].…”

Section: Introductionmentioning

confidence: 99%

Exposure to Benzo(a)pyrene Enhances Acetaminophen-Induced Liver Injury in Mice at Non-Hepatotoxic Doses

Montero-Pérez,

Olivero-Verbel

2024

Sci. Pharm.

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Acetaminophen (APAP) is a widely used analgesic, especially for children. Its primary mechanism involves inhibiting cyclooxygenase enzymes and activating the endocannabinoid and TRPV1 systems. Though its toxicity is low, it can harm the liver in a dose-dependent manner. Low APAP doses can also increase pollutant-induced liver damage. Little is known about interactions between APAP and benzo[a]pyrene (B[a]P). This study aimed to assess if co-exposure to non-hepatotoxic doses of B[a]P and APAP causes liver injury in mice, exploring the underlying mechanisms. Female ICR mice received 50 mg/kg B[a]P or a vehicle for three days, followed by 200 mg/kg APAP or a vehicle. Liver injury was assessed through histopathological examination, serum transaminase activity, and gene expression analysis. In the B[a]P/APAP group, several histology changes were observed, including ballooning injury, steatosis, necrosis, inflammation, and apoptosis. Transaminase levels correlated with histopathological scores, and there was an increase in hepatic cytochrome P450 family 1 subfamily a member 1 (Cyp1a1) mRNA levels and a decrease in aryl hydrocarbon receptor (Ahr), cytochrome P450 family 2 subfamily e polypeptide 1 (Cyp2e1), superoxide dismutase 1 (Sod1), peroxisome proliferator activated receptor gamma (Ppar-γ), and caspase 3 (Casp3). This suggests that prior exposure to B[a]P makes mice more susceptible to APAP-induced liver injury, involving changes in gene expression related to metabolism, redox balance, and cell proliferation. Therefore, using therapeutic APAP doses after exposure to B[a]P could lead to liver injury.

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Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity

Cited by 2 publications

References 27 publications

Fructose as a novel nutraceutical for acetaminophen (APAP)-induced hepatotoxicity

Fructose as a novel nutraceutical for acetaminophen (APAP)-induced hepatotoxicity

Exposure to Benzo(a)pyrene Enhances Acetaminophen-Induced Liver Injury in Mice at Non-Hepatotoxic Doses

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