Toxicological effects of nano- and micro-polystyrene plastics on red tilapia: Are larger plastic particles more harmless?

Plastic debris at the micro-, and potentially also the nano-scale, are widespread in the environment. Microplastics have accumulated in oceans and sediments worldwide in recent years, with maximum concentrations reaching 100 000 particles m(3). Due to their small size, microplastics may be ingested by low trophic fauna, with uncertain consequences for the health of the organism. This review focuses on marine invertebrates and their susceptibility to the physical impacts of microplastic uptake. Some of the main points discussed are (1) an evaluation of the factors contributing to the bioavailability of microplastics including size and density; (2) an assessment of the relative susceptibility of different feeding guilds; (3) an overview of the factors most likely to influence the physical impacts of microplastics such as accumulation and translocation; and (4) the trophic transfer of microplastics. These findings are important in guiding future marine litter research and management strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cytochromes P450 (CYP) are a major source of variability in drug pharmacokinetics and response. Of 57 putatively functional human CYPs only about a dozen enzymes, belonging to the CYP1, 2, and 3 families, are responsible for the biotransformation of most foreign substances including 70-80% of all drugs in clinical use. The highest expressed forms in liver are CYPs 3A4, 2C9, 2C8, 2E1, and 1A2, while 2A6, 2D6, 2B6, 2C19 and 3A5 are less abundant and CYPs 2J2, 1A1, and 1B1 are mainly expressed extrahepatically. Expression of each CYP is influenced by a unique combination of mechanisms and factors including genetic polymorphisms, induction by xenobiotics, regulation by cytokines, hormones and during disease states, as well as sex, age, and others. Multiallelic genetic polymorphisms, which strongly depend on ethnicity, play a major role for the function of CYPs 2D6, 2C19, 2C9, 2B6, 3A5 and 2A6, and lead to distinct pharmacogenetic phenotypes termed as poor, intermediate, extensive, and ultrarapid metabolizers. For these CYPs, the evidence for clinical significance regarding adverse drug reactions (ADRs), drug efficacy and dose requirement is rapidly growing. Polymorphisms in CYPs 1A1, 1A2, 2C8, 2E1, 2J2, and 3A4 are generally less predictive, but new data on CYP3A4 show that predictive variants exist and that additional variants in regulatory genes or in NADPH:cytochrome P450 oxidoreductase (POR) can have an influence. Here we review the recent progress on drug metabolism activity profiles, interindividual variability and regulation of expression, and the functional and clinical impact of genetic variation in drug metabolizing P450s. Copyright © 2013 Elsevier Inc. All rights reserved.