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.

Copper nanoparticles as modulator of active bacterial population and their physiology in ecosphere

The widespread use of nanoparticles (NPs) in industrial and consumer products has resulted in their emergence as significant environmental contaminants that can potentially modulate the role of bacteria in environment. This study examines the impact of different sizes of Copper nanoparticles (CuNPs) on the population and physiology of environmentally relevant gram positive (Bacillus) and gam negative (Alcaligenes, and Pseudomonas) bacteria. In general, exposure to CuNPs resulted in 4 to >6 log inactivation in bacterial population. More specifically, after 2hr exposure of Alcaligenes and Pseudomonas to 50 CuNPs, 5.75 and 6.64 log reduction noted, respectively; and their exposure to 100 CuNPs resulted in 5.97 and 6.58 log reduction, respectively. A similar exposure of laboratory and environmental isolates of Bacillus to 50 and 100 CuNPs resulted in 4.84, 4.16 and 4.35, 3.61 log reduction, correspondingly. The exposure induced elicitation of different toxicity pathways in the test bacteria. Bacterial exposure to 50 CuNPs resulted in elevated levels of LDH in Pseudomonas, in contrast these levels decreased in Alcaligenes and Bacillus. Our toxicity studies showed that exposure to CuNP can have various levels of metabolic and cellular modulation in bacterial species, suggesting that the presence of CuNPs in environment can potentially impact the pollutants-attenuation-role of bacteria in environments such as wastewater biological treatment processes.

Dependence of Graphene Oxide (GO) Toxicity on Oxidation Level, Elemental Composition, and Size

The mass production of graphene oxide (GO) unavoidably elevates the chance of human exposure, as well as the possibility of release into the environment with high stability, raising public concern as to its potential toxicological risks and the implications for humans and ecosystems. Therefore, a thorough assessment of GO toxicity, including its potential reliance on key physicochemical factors, which is lacking in the literature, is of high significance and importance. In this study, GO toxicity, and its dependence on oxidation level, elemental composition, and size, were comprehensively assessed. A newly established quantitative toxicogenomic-based toxicity testing approach, combined with conventional phenotypic bioassays, were employed. The toxicogenomic assay utilized a GFP-fused yeast reporter library covering key cellular toxicity pathways. The results reveal that, indeed, the elemental composition and size do exert impacts on GO toxicity, while the oxidation level exhibits no significant effects. The UV-treated GO, with significantly higher carbon-carbon groups and carboxyl groups, showed a higher toxicity level, especially in the protein and chemical stress categories. With the decrease in size, the toxicity level of the sonicated GOs tended to increase. It is proposed that the covering and subsequent internalization of GO sheets might be the main mode of action in yeast cells.