Current opinion in toxicology最新文献

Abuse of illicit drugs is a growing problem across the world, with rates of drug use and overdose increasing for most major classes of substances. In addition to the social and public health implications of drug abuse, these drugs have a multitude of toxicities affecting all major organ systems. Depending on the drug, dosage, and route of administration, different toxicity profiles are seen. Based on findings from both animal models and human studies, oxidative stress is increasingly recognized as a common underlying etiology for many of the adverse effects seen. In addition to toxicities, oxidative stress also is shown to play a role in addiction and withdrawal. A thorough understanding of the role of oxidative stress in these conditions is key for future research to design therapeutic agents to better prevent and treat toxicities.

Enzymes, nonenzymatic total antioxidant capacity and reactive oxygen species-induced modifications on lipids, DNA and proteins are usually used to evaluate oxidative stress (OS) in humans. Asymmetric dimethylarginine (ADMA) has been suggested as a new OS marker. Antioxidant status may be improved by exogenous antioxidant intake or endurance training, which increases cardiorespiratory fitness (CRF). We reviewed studies on both OS markers and CRF. All markers were affected by age, gender, health, and exercise type. Exercise training with or without antioxidant interventions improved CRF and/or OS old markers, whereas more studies are needed for ADMA. CRF has high clinical significance and its measure should be included in the health assessment and in the redox status evaluated through OS markers.

Cadmium (Cd), one of the most important environmental pollutants, can cause a number of toxic effects. These effects are the result of more than one mechanisms of toxicity, all interrelated in their complexity. Thus, it is difficult to identify a fine line between these mechanisms of Cd toxicity, making their understanding highly complicated. The most important mechanisms by which Cd manifests its toxic effects include changes in gene expression and inhibition of damaged DNA repair, interference of apoptosis and autophagy, oxidative stress, and interaction with bioelements. In this review, we will give a brief overview of the recent developments and findings on the most relevant general and specific mechanisms and molecular pathways of Cd toxicity.

The extent of human exposure to chemicals, their endocrine-disrupting mechanisms of action, and the relationship between exposure and various human diseases raise significant scientific and public health concerns. Polychlorinated biphenyls (PCBs) belong to the group of organic compounds known as persistent organic pollutants, characterized by long-range transport, persistence, bioaccumulation, and high toxicity. They have been identified as endocrine-disrupting chemicals. In vivo and in vitro studies have shown that endocrine-disrupting effects of PCBs mainly involve thyroid and reproductive function. In the review presented, these effects were placed in the context of the most recent findings on PCB-induced endocrine-disrupting mechanisms and modes of action.

Engineered nanomaterials (ENMs) are unique in our modern industrial world; however, limited information is currently available regarding exposure and hazard information, including the genotoxicity of such materials. Much work remains to be carried out for developing, validating, and harmonizing a tool chest for the genotoxicity of nanomaterials. Gaps remain in our understanding of potential mechanisms of the genotoxicity of nanomaterials. Until more appropriate tests are available for testing of ENMs, the potential impact of ENMs may continue to be underestimated without proper consideration of the genotoxicity potential of such materials. Clearly, resources need to be devoted to better approaches to the hazard identification of nanomaterials to insure safe development and application of nanotechnology and for the protection of human health and the environment.

The decline of male fertility has become a serious public health concern over the last decades, coinciding with an increase in environmental exposure to toxic pollutants. Toxic elements cadmium (Cd), arsenic (As), and lead (Pb) seem to contribute to declining fertility in men through progressive impairment of semen quality. Reproductive toxicity of these elements is mediated by multiple mechanisms. Although experimental animal studies generally support an adverse role of Cd, As, and Pb in human reproduction issues, data on the effects induced by the levels of toxic elements that represent environmental exposure are inconsistent. This review summarizes reports from experimental studies in animals and epidemiological observational findings from environmental exposure to Cd, As, and Pb, with special focus on semen quality parameters as the indicator of male fertility.

A massive-scale production of engineered nanoparticles (ENPs) becomes one of the most important environmental issues. The mechanisms of ENPs' (eco)toxic action are not fully understood, and the estimation of those mechanisms is a complicated task because even slight changes in particle characteristics could dramatically change their toxicity. As a result of continuous manufacturing of ENPs with specific functionality and different physicochemical properties, conventional methods of in vivo and in vitro testing would not be able to fill the existing knowledge gap in nanotoxicology. The objectives of this review are to overlook the current achievements based on the new approaches of ENPs' risk assessment, such as bioinformatics approaches and machine learning tools. These methods confirmed their ability to reliable prediction and evaluation of ENPs' behavior and their toxic endpoints. Databases and projects based on these methods and approaches would be highly useful in addressing the problem of ENPs’ regulation.

Metals qualitatively dominate the chemical elements found on Earth, but life has found a use for only a minority of them. Most metals are mobilized as cations, and thereby interact and are processed by living species. Animals are exposed to environmental metals at chronic low concentrations through food, air particles, and other ways, under conditions that are too rarely reproduced in laboratory settings. Actual metal detoxification systems in animals are not many and of limited efficiency which casts doubt on the existence of any safe concentration — a threshold for nonessential metals. Hence the mechanisms of action of toxic metals at very low doses still have to be adequately addressed to provide means for knowledge-based risk assessment that is increasingly requested by diverse communities.

We are continuously exposed to large numbers of nonbiological, persistent particulates through dermal, oral and inhalation routes. At sizes perfect for cell interactions, such modern particle exposures are derived from human engineering either purposefully (e.g. additives/excipients) or inadvertently (e.g. pollution). Whether oral or dermal exposure to common particles has significant adverse effects is not yet known. However, relationships between increased morbidity or mortality and airborne particle exposure are well established. Large nanoparticles and microparticles adsorb environmental molecules, including antigens and allergens, and deliver them to cells potentially with an adjuvant effect. Smaller nanoparticles may have enhanced redox activity because of increased surface areas or band gap effects. Under some circumstances, ultrasmall nanoparticles can ligate cellular receptors or interact with other cell machinery and drive distinct cell signalling. These, as well as the potential for inflammasome activation, are discussed as feasible pathways to understanding or debunking particle toxicity.

There is a growing body of evidence that various pesticides and heavy metals are carcinogenic. If not directly, there is also evidence that shows that these compounds can participate in carcinogenesis in a passive or permissive role, facilitating other compounds from inducing tumor formation. Little evidence is available to aid in understanding the toxicity of metal-pesticide mixtures. In many instances, exposure to subclinical, or subtoxic, levels would be asymptomatic under a single-chemical exposure. But, we do not know how these compounds would act together. A synergistic or potentiating response could be highly possible. By chemically interacting with the environment, as well as each other, metal pesticide mixtures may yield unpredictable toxicity. Because we are not exposed to a single xenobiotic at a time, the importance of studying the toxicity of mixtures has never been more critical.