Current Opinion in Toxicology最新文献

Perception of hormesis as a significant dose–response phenomenon is found in many sciences without predicting and/or quantifying this low-dose effect with statistical models. Only a minority of papers published on hormesis in plant biology or other sciences apply available statistical modelling of the dose–response relationships, along with significance testing for hormesis and prediction of sub-NOAEL quantities. The prediction of threshold quantities opens many further evaluation options such as risk assessment, hormesis in mixtures or in risk groups, selective hormesis in populations, or assessment of transgenerational hormesis. Therefore, the significance and value of hormesis research can benefit significantly from sound modelling of this biphasic phenomenon. This review is meant to raise awareness of scientists for the value of hormesis modelling.

Research on the biology of aging and possibilities of interventions has gained a significant push forward by incorporating the concept of mild stress-induced physiological hormesis. Mild stress induced-activation of adaptive and protective pathways in cells and organisms has numerous health-promoting, aging-modulatory and lifespan-extending effects. Moderate and repeated physical exercise is the paradigm for physiological hormesis. Molecular mechanisms for the action of hormetins comprise a cascade of primary stress response pathways, including oxidative stress response, heat shock response, unfolded protein stress response, autophagy, DNA damage response, inflammatory response and sirtuin activation response. Hormetin-based strengthening of the organismic ability of homeodynamics or dynamic homeostasis is a promising holistic approach towards health maintenance, recovery, and promotion for healthy aging and longevity.

Many studies report negative associations between exposure to large concentrations of contaminants and life-history traits of animals. As a consequence, they argue to derive linear models that can be applied to predict effects in sub-threshold or low-dose exposure scenarios. However, several recent studies found that exposure to low doses of a contaminant may induce a hormetic response, i.e. stimulatory or beneficial effects at low concentrations, but harmful effects at higher concentrations. Hormesis might be a novel fundamental pillar in the field of ecotoxicology, as it may promote the evolution of adaptive coping mechanisms in rapidly changing and challenging environments. However, because hormesis occurs in the low-dose zone of the dose–response, it has been often neglected. In this review, we have discussed how low-dose contaminant exposure may adaptively modify molecular and physiological mechanisms that may lead to organisms better capable of coping with challenging environments, how such responses may be transgenerational, and how thus this issue can no longer be ignored in ecotoxicological studies. In so doing, we have also identified some of the main limitations of ecotoxicological studies that, by masking potential hormetic responses of animals to chemicals, make the integration of hormesis complicated to achieve.

The hormetic dose–response has been frequently reported in a diverse set of microbial species. However, the role of energy source or substrate in microbial hormesis has not attracted enough attention. Here, we review recently published studies regarding the hormetic phenomena of exogenous chemicals’ effects on microbes under different energy/substrate conditions. Energy/substrate could regulate metabolic activity, population density, carbon catabolite repression pathway, or quorum sensing system to decide the survival strategies of microbes under exogenous stress, ultimately influencing the dose–response feature and even the occurrence of the hormetic phenomenon. This review highlights the key role of energy/substrate in microbial hormesis, which could not only provide a new insight into the investigation of hormetic effects in microbes but also promote the development of microbe-related fields.

There are various paths of interactions of combination of two or more chemicals with biological systems. The response of chemicals in a mixture can be predicted employing the perceptions of concentration or dose addition for chemicals with identical mode of action (MOA) and/or common target of effect. While response addition can be considered for chemicals acting on diverse biological targets. Both hypotheses are feasible only when there is no interaction between chemicals. On the contrary, if interaction occurs between chemicals in a mixture results in synergism or potentiation if induction of activating enzyme/inhibition of detoxifying enzyme happens. In contrast, competition of individual chemicals at biological target site show antagonism. Experimental models are time-consuming and costly. Diversity of mixtures and the necessity to test multiple organisms covering different ecosystems to avail the toxicity data make the experimentalist job more challenging. There comes the importance of computational approaches, proven and efficient alternatives to fill the toxicity data gaps, prioritization of chemicals, identification of the toxicity mechanism, and risk assessment and management.

Microplastic particles are global pollutants which have been measured in drinking water, dust, and some food items. Concerns about population exposures and the resulting risks to human health are increasing. Because the gut can be considered one of the primary sites for microplastic exposure in the human body, here, we explore the possible impact of ingested microplastic particles on gastrointestinal ecology, providing some evidence for their active role as a driver of dysbiotic variation in the human gut microbiome. This further stresses the urgent need to quantitatively assess both oral exposure and hazards of microplastic in the human gut, enabling prediction of the levels of microplastic risk and outcomes of dysbiotic changes in the gut microbiome to be inferred.

Plastic contamination by micro(nano)plastics represents one of the main threats that ecosystems have to currently face. The impact of micro(nano)plastics on organisms and ecosystems is not fully understood neither in the field nor the laboratory because of the lack of analytical methods that allow to accurately detect and quantify the exposure. This is particularly true for small sized microplastics and nanoplastics, whose quali-quantification is troublesome. Different analytical techniques can be used to measure micro(nano)plastics levels in different matrices, but recently the application of thermal analysis emerged as a promising approach. This review highlights the importance and the advantages of thermal analyses to assess the exposure to micro(nano)plastics in ecotoxicological and toxicological studies.

The increasing abuse of psychoactive drugs represents a global public health burden, as recurrent exposure to these substances can cause neurodegeneration, premature ageing and negatively impact normal neurodevelopment. Although the basis of such neurotoxic effects is not completely elucidated, compelling evidence has shown that dysregulation of neurotransmission, disruption of mitochondrial function and dynamics, overproduction of ROS, impairment of neuroimmunomodulation, and epigenetic alterations are caused by many psychoactive substances (e.g., alcohol, cannabinoids, opioids, amphetamines and cocaine). Understanding the neurotoxicological profiles of psychoactive substances and the underlying pathways assumes major importance towards reaching improved risk assessment and treatment of drug use disorders. As such, we herein reviewed the most recent updates on the respective drug-induced cellular and molecular mechanisms.