Current Opinion in Toxicology最新文献

Drug-induced nephrotoxicity is a major cause of kidney dysfunction with potentially fatal consequences and can hamper the research and development of new pharmaceuticals. This emphasises the need for new methods for earlier and more accurate diagnosis to avoid drug-induced kidney injury. Here, we present a systematic review of the available approaches to study drug-induced kidney injury, as one of the most common reasons for drug withdrawal, in vitro. The systematic review approach was selected to ensure that our findings are as objective and reproducible as possible. A novel study quality checklist, named validation score, was developed based on published regulatory guidance and industrial perspectives, and models returned by the search strategy were analysed as per their overall complexity and the kidney region studied. Our search strategy returned 1731 articles supplemented by 337 from secondary sources, of which 57 articles met the inclusion criteria for final analysis. Our results show that the proximal tubule dominates the field (84%), followed by the glomerulus and Bowman's capsule (7%). Of all drugs investigated, the focus was most on cisplatin (n = 29, 50.1% of final inclusions). We found that with increasing model complexity the validation score increased, reflecting the value of innovative in vitro models. Furthermore, although the highly diverse usage of cell lines and modelling approaches prevented a strong statistical verification through a meta-analysis, our findings show the downstream potential of such approaches in personalised medicine and for rare diseases where traditional trials are not feasible.

Owing to modern-day urbanization and industrial activities, heavy metal pollution and its environmental impact have drawn the attention of the scientific community towards itself. Among all the heavy metals, cadmium is known to have no biological function, and its presence harms almost all life forms. Cadmium (Cd) has natural and anthropogenic sources of entry into the ecosystem. It is nonbiodegradable and is present in different trophic levels in the food chain, raising concern over food safety. The bioavailability, bioaccessibility, and accumulation of Cd in soil-plant systems are the main drivers of its transfer to different trophic levels via diverse routes. In the human system, bioaccumulation of Cd disrupts the antioxidant defense system due to induced oxidative stress as a result of reactive oxygen species generation, which further causes different ailments. This review provides an update on the effects of Cd exposure on the soil-plant system, food safety, and human health, focusing on the various mechanisms involved in cellular or molecular alterations.

Lead (Pb) and mercury (Hg) are metals widely recognized as global pollutants, constituting public health problems. This review presents the extent of Pb and Hg human exposure in Latin America and associated health effects on different population groups. The results showed that the highest Pb levels occurred in occupational battery recycling environments. In the case of Hg, alarming levels were found in indigenous populations of the Colombian and Brazilian Amazon. The evidence gathered from this review encourages conducting collaborative research in countries with minimal or null information on the subject, and highlights the need for a strong framework to create legislation and massive educational efforts to halt, in a timely and effective manner, anthropogenic activities that expose Latin American populations.

The development of new medicines suffers from attrition, especially in the development pipeline. Eight out of nine drug candidates entering the clinical testing phase fail, mostly due to poor safety and efficacy. The low predictive value of animal models, used in earlier phases of drug development, for effects in humans poses a major problem. In particular, drug disposition can markedly differentiate in experimental animals versus humans. Meanwhile, classic in vitro methods can be used but these models lack the complexity to mimic holistic physiological processes occurring in the human body, especially organ–organ interactions. Therefore, better predictive methods to investigate drug disposition in the preclinical phase are needed, for which recent developments in multiorgan-on-chip methods are very promising. To be able to capture human physiology as good as possible, multiorgan-on-chips should feature 1) human cells endogenously expressing main transporters and metabolizing enzymes; 2) organ models relevant for exposure route; 3) individual organs-on-chip connected in a physiologically relevant manner; 4) a tight cellular barrier between the compartments; 5) organ models properly polarized in 3D; 6) allow for sampling in all major compartments; 7) constructed from materials that do not absorb or adsorb the compound of interest; 8) cells should grow in absence of fetal calf serum and Matrigel; 9) validated with a panel of compounds with known characteristics in humans; 10) an integrated computer model translating concentrations to the human situation. Here, an overview of available systems is presented and the difficult route towards a fully validated system is discussed.

The word ‘plastic’ originates from the Ancient Greek ‘plastikos’, meaning shapeable, moldable. This trait has significantly contributed to its popularity and rapid global increase in use in recent decades, while also presenting immense challenges for its detection, identification, and quantification in marine ecosystems. Here, we review the current methods in marine plastic assessment and present the main challenges in monitoring plastic pollution in marine environments. We also focus on plastic and its additives’ interactions with biological systems and the urgent need to establish standardization of the methodologies and techniques worldwide to enable accurate evaluations and comparisons of plastic pollution and further our understanding of its impact on marine organisms and ecosystems.

Plastic pollution is ubiquitous, and the presence of plastic particles available for human uptake is documented, for example, in air, foodstuffs, and drinking water. Meanwhile, researchers, organizations, and policy agencies call for large-scale analyses of plastic pollution exposure. Doing precisely this in neighboring research fields, we argue that citizen science (CS) can contribute to close knowledge gaps for human exposure. We reviewed the recent literature (2019-present) on the assessment of human exposure to plastic pollution using CS to document the state-of-the-art and only found a single study. We discuss the strength of citizen-generated evidence regarding the most prominent exposure routes, and we present an example of a future, large-scale CS project assessing plastic exposure via drinking water.

Plastics have overwhelmingly been employed in every sector of human life, ranging from the cosmetics and food industry to transportation and electronics. It resulted in emerging plastic pollution worldwide, which poses serious threats to the natural ecosystem and human health. This mini-review highlights human exposure to micro(nano)plastics in the environment and evaluates bioplastics as a health/environment safer option.

The COVID-19 pandemic led to a sudden global increase in the production, consumption, and mismanagement of personal protective equipment (PPE). As plastic-based PPE such as disposable face masks and gloves have become widely used, human exposure to PPE-derived pollutants may occur through indirect and direct pathways. This review explores the potential health impacts related to plastic-based PPE through these pathways. Face masks release microplastics, which are directly inhaled during use or transported through the environment. The latter can adsorb chemical contaminants and harbor pathogenic microbiota, and once consumed by organisms, they can translocate to multiple organs upon intake, potentially causing detrimental and cytotoxic effects. However, more research is required to have a comprehensive overview of the human health effects.

Heavy metals are ubiquitous in nature and their bioaccumulation usually remains undetected until it manifests as a chronic pathological condition. Accumulating evidence suggests that all age groups (independent of socioeconomic status, race, gender, and geographical location) and organs are susceptible to metal induced toxicity, although the impact on the central nervous system is more severe and long-lasting in both developing and adult human brain. There are no clinically proven treatments to those affected by heavy metal toxicity. We here review the most recent studies (2018–2020) on the differential impact of heavy metals on the pathogenesis of various neurodevelopmental disorders in children and neurodegenerative diseases in adults, highlighting the need for urgent intervention to this global health crisis.