The ubiquitous presence of microplastics in the environment has drawn the attention of ecotoxicologists on its safety and toxicity. Sources of microplastics in the environment include disintegration of larger plastic items (secondary microplastics), personal care products like liquid soap, exfoliating scrubbers, and cleaning supplies etc. Indiscriminate usage of plastics and its poor waste disposal management pose serious concern on ecosystem quality at global level. The present review focused on the ecological impact of microplastics on biota at different trophic levels, its uptake, accumulation, and excretion etc., and its plausible mechanistic toxicity with risk assessment approaches. Existing scientific evidence shows that microplastics exposure triggers a wide variety of toxic insult from feeding disruption to reproductive performance, physical ingestion, disturbances in energy metabolism, changes in liver physiology, synergistic and/ or antagonistic action of other hydrophobic organic contaminants etc. from lower to higher trophics. Thus, microplastic accumulation and its associated adverse effects make it mandatory to go in for risk assessment and legislative action. Subsequent research priorities, agenda, and key issues to be addressed are also acknowledged in the present review.
Nrf2, a redox sensitive transcription factor, plays a pivotal role in redox homeostasis during oxidative stress. Nrf2 is sequestered in cytosol by an inhibitory protein Keap1 which causes its proteasomal degradation. In response to electrophilic and oxidative stress, Nrf2 is activated, translocates to nucleus, binds to antioxidant response element (ARE), thus upregulates a battery of antioxidant and detoxifying genes. This function of Nrf2 can be significant in the treatment of diseases, such as cancer, neurodegenerative, cardiovascular and pulmonary complications, where oxidative stress causes Nrf2 derangement. Nrf2 upregulating potential of phytochemicals has been explored, in facilitating cure for various ailments while, in cancer cells, Nrf2 upregulation causes chemoresistance. Therefore, Nrf2 emerges as a key regulator in oxidative stress-mediated diseases and Nrf2 silencing can open avenues in cancer treatment. This review summarizes Nrf2-ARE stress response mechanism and its role as a control point in oxidative stress-induced cellular dysfunctions including chronic inflammatory diseases.
In their reductionist approach in unraveling phenomena inside the cell, scientists in recent times have focused attention to mitochondria. An organelle with peculiar evolutionary history and organization, it is turning out to be an important cell survival switch. Besides controlling bioenergetics of a cell it also has its own genetic machinery which codes 37 genes. It is a major source of generation of reactive oxygen species, acts as a safety device against toxic increases of cytosolic Ca2+ and its membrane permeability transition is a critical control point in cell death. Redox status of mitochondria is important in combating oxidative stress and maintaining membrane permeability. Importance of mitochondria in deciding the response of cell to multiplicity of physiological and genetic stresses, inter-organelle communication, and ultimate cell survival is constantly being unraveled and discussed in this review. Mitochondrial events involved in apoptosis and necrotic cell death, such as activation of Bcl-2 family proteins, formation of permeability transition pore, release of cytochrome c and apoptosis inducing factors, activation of caspase cascade, and ultimate cell death is the focus of attention not only for cell biologists, but also for toxicologists in unraveling stress responses. Mutations caused by ROS to mitochondrial DNA, its inability to repair it completely and creation of a vicious cycle of mutations along with role of Bcl-2 family genes and proteins has been implicated in many diseases where mitochondrial dysfunctions play a key role. New therapeutic approaches toward targeting low molecular weight compounds to mitochondria, including antioxidants is a step toward nipping the stress in the bud.
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