Acetaminophen pharmacokinetic and toxicological aspects: a review

Paracetamol (Tylenol®) is a widely used non-steroidal anti-inflammatory drug responsible for many cases of intoxication and liver failure. When taken orally, it is absorbed and begins to be digested in the stomach. Paracetamol is primarily metabolized by the liver via phase I and phase II enzymes (glucuronyltransferases and sulfotransferases). When present in excess in the body, it forms an active metabolite known as N-acetyl-para-benzoquinone-imine (NAPQI). This metabolite is a reactive species capable of binding to living cells and proteins causing injuries and adducts, which are largely responsible for damage, especially the liver. The study of paracetamol pharmacokinetics is important to understand its toxicity pathways and thus develop new therapies to prevent or minimize the damage caused by this drug. This review sought some of the most relevant works that address the pharmacokinetics of paracetamol to facilitate a general understanding of what has been discovered so far on the subject. This study also aims to make patients aware of the possible harm that can occur when this drug is indiscriminately used.

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Toxicodynamic aspects and new tools for assessing acetaminophen toxicity: a review

Panorama brasileiro de tungstênio (w) entre os anos de 2008 e 2014 ◽

10.32749/nucleodoconhecimento.com.br/health/assessing-acetaminophen ◽

2021 ◽

pp. 28-38

Author(s):

Fernando Wendel Franco ◽

Maíra Casali Malonn

Keyword(s):

Messenger Rna ◽

Active Metabolite ◽

Liver Toxicity ◽

Living Cells ◽

The Body ◽

Micro Rna ◽

Mechanisms Of Toxicity ◽

Acetaminophen Toxicity ◽

The Subject ◽

Toxicity Mechanisms

Acetaminophen (Tylenol®) or APAP is a widely used non-steroidal anti-inflammatory drug responsible for many cases of intoxication, suicide, and liver toxicity. Due to its toxicity mechanisms are not yet fully elucidated and this literature review aims to objectively bring some of the most recent and relevant scientific discoveries that can help in the understanding of the subject. After being ingested, paracetamol is absorbed and begins to be digested in the stomach, then being metabolized by the liver through phase I and phase II (glucuronyltransferases and sulfotransferases). When present in excess in the body, APAP forms an active metabolite known as N-acetyl-para-benzoquinone-imine (NAPQI). This metabolite is a reactive species capable of binding to living cells and proteins causing damages, which are largely responsible for injuries, especially in the liver. As a conclusion of this study, it can be inferred that the lesions caused by acetaminophen, in addition to protein adducts, also extend to mitochondria and proteins. New markers, in addition to enzymes already known from the CYP families, also include proteins and cytokines, in addition to molecular methods, messenger RNA and micro RNA have been used to study hepatotoxicity by APAP. This makes it easier to deeply understand the mechanisms of toxicity induced by acetaminophen and then to advance in studies with new therapies.

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Analysis of the ex-vivo transformation of semen, saliva and urine as they dry out using ATR-FTIR spectroscopy and chemometric approach

Scientific Reports ◽

10.1038/s41598-021-91009-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tanurup Das ◽

Abhimanyu Harshey ◽

Ankit Srivastava ◽

Kriti Nigam ◽

Vijay Kumar Yadav ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Ex Vivo ◽

Body Fluids ◽

Biochemical Changes ◽

Partial Least Square ◽

The Body ◽

Slow Phase ◽

Time Since Deposition ◽

Dry Out

AbstractThe ex-vivo biochemical changes of different body fluids also referred as aging of fluids are potential marker for the estimation of Time since deposition. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. The present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., semen, saliva, and urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to the major contribution of water and faster Phase II due to significant evaporation of water. Two spectral regions i.e., 3200–3400 cm−1 and 1600–1000 cm−1 are the major contributors to the spectra of these fluids. Several peaks in the spectral region between 1600 and 1000 cm−1 showed highly significant regression equation with a higher coefficient of determination values in Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the time since deposition of the aforesaid fluids as they dry out. Additionally, this study potentially estimates the time since deposition of an offense from the aging of the body fluids at the early stages after its occurrence as well as works as the precursor for further studies on an extended timeframe.

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