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1.
Drug Metab Dispos ; 50(4): 500-507, 2022 04.
Article in English | MEDLINE | ID: mdl-34930784

ABSTRACT

Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a stress-activated transcription factor that is highly responsive to oxidative stress and electrophilic stimuli. Upon activation, Nrf2 upregulates a battery of cytoprotective genes meant to prevent cell death or damage. In many models of inflammation, Nrf2 protects against the immune response and decreases injury, including in the context of asthma and allergy. However, in some models of asthma and allergy, Nrf2 either does not play a role or can even exacerbate inflammation. In general, the reasons behind these discrepancies are not clear and the mechanisms by which Nrf2 modulates immune response are largely uncharacterized. The aim of this review is to highlight current literature assessing the role of Nrf2 in allergy and asthma to understand Nrf2 as a potential therapeutic target. SIGNIFICANCE STATEMENT: Nuclear factor erythroid-derived 2-like 2 (Nrf2) is an important immune mediator that modulates numerous immune cell types in various inflammatory diseases, including allergy and asthma. There is considerable interest in Nrf2 as a drug target in inflammation, which is complicated by the complex nature of Nrf2 in the immune system. This review focuses on the role of Nrf2 in asthma and allergy, including in regulating immune cell function and in detoxifying xenobiotics that exacerbate these diseases.


Subject(s)
Asthma , Hypersensitivity , NF-E2-Related Factor 2 , Humans , Inflammation/metabolism , NF-E2-Related Factor 2/genetics , Oxidative Stress/physiology , Signal Transduction/physiology
2.
Chemosphere ; 239: 124786, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31520975

ABSTRACT

The herbicide atrazine is heavily applied in agricultural areas in the Midwestern United States and can run-off and seep into surrounding aquatic habitats where concentrations can reach over 300 ppb. It is known that acute exposures to 80 ppb atrazine cause lasting deficiencies in the chemoreception of food and mate odors. Since atrazine impairs chemosensory responses, the goal of this study was to determine the effect of atrazine on cells, including olfactory sensory neurons, located in the lateral antennules of crayfish. In this experiment, we treated crayfish for 10 days with ecologically relevant concentrations of 0, 10, 40, 80, 100 and 300 ppb (µg L-1) of atrazine. Following treatments, the distal portion of the lateral antennules was cryosectioned. We used a TdT mediated dUTP nick-end labeling (TUNEL) assay to determine if any cells had DNA damage and may be thus undergoing apoptosis. We found that as atrazine concentrations increase above 10 ppb, the number of TUNEL-positive cells, visualized in the lateral antennules, significantly increases. Our data show that atrazine exposure causes DNA damage in cells of the lateral antennules, including olfactory sensory neurons, thus leading to impairments in chemosensory abilities. Because crayfish rely heavily on chemoreception for survival, changes in their ability to perceive odors following atrazine exposure may have detrimental effects on population size.


Subject(s)
Arthropod Antennae/drug effects , Astacoidea/drug effects , Astacoidea/genetics , Atrazine/toxicity , DNA Damage/drug effects , Water Pollutants, Chemical/toxicity , Animals , Arthropod Antennae/cytology , Astacoidea/cytology , Ecotoxicology , Environmental Exposure , Female , Herbicides/toxicity , Male
3.
Bull Environ Contam Toxicol ; 103(4): 579-584, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31273423

ABSTRACT

The herbicide atrazine is heavily applied in the U.S. Midwest to control broadleaf weeds. It enters local streams and rivers through runoff and seepage, and exposure can affect non-target aquatic organisms, like crayfish. We examined sublethal effects of atrazine on the expression and activity of the detoxification enzymes cytochrome P450 (CYP450) and glutathione-S-transferase (GST) in crayfish. Crayfish were exposed to 0, 10, 40, 80, 100 and 300 ppb atrazine for 1, 2, 4, 7 and 10 days. Their hepatopancreas was collected and CYP450 expression and GST activity was analyzed. Atrazine exposure caused differential expression and activity of CYP450 and GST. CYP450 expression varied over exposure concentrations and time. Further, GST activity significantly increased following a 2 day, 10 ppb exposure to atrazine and a 300 ppb atrazine exposure for all days tested. We found that atrazine detoxification is a dynamic process that changes with the length and intensity of atrazine exposure.


Subject(s)
Astacoidea/physiology , Atrazine/toxicity , Cytochrome P-450 Enzyme System/metabolism , Glutathione Transferase/metabolism , Herbicides/toxicity , Animals , Astacoidea/drug effects , Atrazine/metabolism , Environmental Exposure , Glutathione/metabolism , Hepatopancreas/drug effects , Herbicides/metabolism , Rivers , Seafood
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