scholarly journals The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Datis Kharrazian
Keyword(s):  
Autoimmune Disease ◽  
Bisphenol A ◽  
Molecular Mimicry ◽  
Signal Transduction Pathway ◽  
Immune Reactivity ◽  
Cytochrome P450 Enzyme ◽  
Disease Development ◽  
Aryl Hydrocarbon ◽  
P450 Enzyme ◽  
The Impact

Bisphenol A (BPA) is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA’s impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity.

scholarly journals Quantifying the Impact of Phenoconversion on Medications With Actionable Pharmacogenomic Guideline Recommendations in an Acute Aged Persons Mental Health Setting

2021 ◽  
Vol 12 ◽  
Author(s):  
Sam Mostafa ◽  
Thomas M. Polasek ◽  
Leslie J. Sheffield ◽  
David Huppert ◽  
Carl M. J. Kirkpatrick
Keyword(s):  
Mental Health ◽  
Genetic Variants ◽  
Cytochrome P450 Enzyme ◽  
Mental Health Setting ◽  
Care Model ◽  
Collaborative Care Model ◽  
Mental Health Patients ◽  
P450 Enzyme ◽  
Potential Benefits ◽  
The Impact

Introduction: Polypharmacy and genetic variants that strongly influence medication response (pharmacogenomics, PGx) are two well-described risk factors for adverse drug reactions. Complexities arise in interpreting PGx results in the presence of co-administered medications that can cause cytochrome P450 enzyme phenoconversion.Aim: To quantify phenoconversion in a cohort of acute aged persons mental health patients and evaluate its impact on the reporting of medications with actionable PGx guideline recommendations (APRs).Methods: Acute aged persons mental health patients (N = 137) with PGx and medication data at admission and discharge were selected to describe phenoconversion frequencies for CYP2D6, CYP2C19 and CYP2C9 enzymes. The expected impact of phenoconversion was then assessed on the reporting of medications with APRs.Results: Post-phenoconversion, the predicted frequency at admission and discharge increased for CYP2D6 intermediate metabolisers (IMs) by 11.7 and 16.1%, respectively. Similarly, for CYP2C19 IMs, the predicted frequency at admission and discharge increased by 13.1 and 11.7%, respectively. Nineteen medications with APRs were prescribed 120 times at admission, of which 50 (42%) had APRs pre-phenoconversion, increasing to 60 prescriptions (50%) post-phenoconversion. At discharge, 18 medications with APRs were prescribed 122 times, of which 48 (39%) had APRs pre-phenoconversion, increasing to 57 prescriptions (47%) post-phenoconversion.Discussion: Aged persons mental health patients are commonly prescribed medications with APRs, but interpretation of these recommendations must consider the effects of phenoconversion. Adopting a collaborative care model between prescribers and clinical pharmacists should be considered to address phenoconversion and ensure the potential benefits of PGx are maximised.

scholarly journals Effects of Deoxynivalenol and Fumonisins on Broiler Gut Cytoprotective Capacity

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 729
Author(s):  
Vasileios Paraskeuas ◽  
Eirini Griela ◽  
Dimitrios Bouziotis ◽  
Konstantinos Fegeros ◽  
Gunther Antonissen ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Antioxidant Response ◽  
Cytochrome P450 Enzyme ◽  
Poultry Production ◽  
Gut Health ◽  
Bioactive Components ◽  
Site Specific ◽  
Aryl Hydrocarbon ◽  
Crucial Problem ◽  
P450 Enzyme

Mycotoxins are a crucial problem for poultry production worldwide. Two of the most frequently found mycotoxins in feedstuffs are deoxynivalenol (DON) and fumonisins (FUM) which adversely affect gut health and poultry performance. The current knowledge on DON and FUM effects on broiler responses relevant for gut detoxification, antioxidant capacity, and health is still unclear. The aim of this study was to assess a range of selected molecular intestinal biomarkers for their responsiveness to the maximum allowable European Union dietary levels for DON (5 mg/kg) and FUM (20 mg/kg) in broilers. For the experimental purpose, a challenge diet was formulated, and biomarkers relevant for detoxification, antioxidant response, stress, inflammation, and integrity were profiled across the broiler intestine. The results reveal that DON significantly (p < 0.05) induced aryl hydrocarbon receptor (AhR) and cytochrome P450 enzyme (CYP) expression mainly at the duodenum. Moreover, DON and FUM had specific significant (p < 0.05) effects on the antioxidant response, stress, inflammation, and integrity depending on the intestinal segment. Consequently, broiler molecular responses to DON and FUM assessed via a powerful palette of biomarkers were shown to be mycotoxin and intestinal site specific. The study findings could be highly relevant for assessing various dietary bioactive components for protection against mycotoxins.

scholarly journals Targeting AhR as a Novel Therapeutic Modality against Inflammatory Diseases

2021 ◽  
Vol 23 (1) ◽  
pp. 288
Author(s):  
Alkeiver S. Cannon ◽  
Prakash S. Nagarkatti ◽  
Mitzi Nagarkatti
Keyword(s):  
Inflammatory Diseases ◽  
The Body ◽  
Environmental Toxins ◽  
Therapeutic Modality ◽  
Cytochrome P450 Enzyme ◽  
Epigenetic Mechanisms ◽  
Aryl Hydrocarbon ◽  
P450 Enzyme ◽  
Environmental Sensor ◽  
Diverse Groups

For decades, activation of Aryl Hydrocarbon Receptor (AhR) was excluded from consideration as a therapeutic approach due to the potential toxic effects of AhR ligands and the induction of the cytochrome P450 enzyme, Cyp1a1, following AhR activation. However, it is now understood that AhR activation not only serves as an environmental sensor that regulates the effects of environmental toxins, but also as a key immunomodulator where ligands induce a variety of cellular and epigenetic mechanisms to attenuate inflammation. Thus, the emergence of further in-depth research into diverse groups of compounds capable of activating this receptor has prompted reconsideration of its use therapeutically. The aim of this review is to summarize the body of research surrounding AhR and its role in regulating inflammation. Specifically, evidence supporting the potential of targeting this receptor to modulate the immune response in inflammatory and autoimmune diseases will be highlighted. Additionally, the opportunities and challenges of developing AhR-based therapies to suppress inflammation will be discussed.

The impact of intrauterine growth restriction on cytochrome P450 enzyme expression and activity

Placenta ◽  
2020 ◽  
Vol 99 ◽  
pp. 50-62
Author(s):  
Grace M. McBride ◽  
Michael D. Wiese ◽  
Jia Yin Soo ◽  
Jack R.T. Darby ◽  
Mary J. Berry ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Cytochrome P450 Enzyme ◽  
Enzyme Expression ◽  
Intrauterine Growth ◽  
P450 Enzyme ◽  
The Impact ◽  
Expression And Activity

Parasitic infection and autoimmunity

Lupus ◽  
2009 ◽  
Vol 18 (13) ◽  
pp. 1144-1148 ◽  
Author(s):  
G. Zandman-Goddard ◽  
Y. Shoenfeld
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Response ◽  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Molecular Mimicry ◽  
Uv Light ◽  
Parasitic Infection ◽  
Systemic Lupus ◽  
Parasitic Load ◽  
The Impact

Systemic lupus erythematosus is the prototypic multi-system autoimmune disease characterized by the production of multiple autoantibodies. The development of disease depends on a genetic predisposition and exposure to environmental factors including UV light, drugs, and infections. The association of parasitic infection and the development of autoimmune disease in general and lupus in particular remains elusive. In this paper, we review the recent evidence for protection from autoimmunity by parasites, models of parasite-related autoimmunity, molecular mimicry, the impact of parasitic molecules on the immune response and the association between parasitic load and the degree of autoimmunity.

scholarly journals Hyposialylation Must Be Considered to Develop Future Therapies in Autoimmune Diseases

2021 ◽  
Vol 22 (7) ◽  
pp. 3402
Author(s):  
Anne Bordron ◽  
Marie Morel ◽  
Cristina Bagacean ◽  
Maryvonne Dueymes ◽  
Pierre Pochard ◽  
...  
Keyword(s):  
Immune System ◽  
Sialic Acid ◽  
Autoimmune Disease ◽  
Disease Development ◽  
Detailed Characterization ◽  
Multiple Factors ◽  
Innovative Therapies ◽  
Future Treatments ◽  
The Impact

Autoimmune disease development depends on multiple factors, including genetic and environmental. Abnormalities such as sialylation levels and/or quality have been recently highlighted. The adjunction of sialic acid at the terminal end of glycoproteins and glycolipids is essential for distinguishing between self and non-self-antigens and the control of pro- or anti-inflammatory immune reactions. In autoimmunity, hyposialylation is responsible for chronic inflammation, the anarchic activation of the immune system and organ lesions. A detailed characterization of this mechanism is a key element for improving the understanding of these diseases and the development of innovative therapies. This review focuses on the impact of sialylation in autoimmunity in order to determine future treatments based on the regulation of hyposialylation.

Polymorphisms in alcohol metabolizing genes ADH2 and ADH3 and susceptibility to pancreatitis in alcoholics

2017 ◽  
Vol 6 (03) ◽  
pp. 5297
Author(s):  
Vedangi Aaren* ◽  
Godi Sudhakar ◽  
Girinadh L.R.S.
Keyword(s):  
Frequency Distribution ◽  
Ethanol Metabolism ◽  
Alcoholic Pancreatitis ◽  
Cytochrome P450 Enzyme ◽  
Increased Risk ◽  
Significant Difference ◽  
Pcr Rflp ◽  
P450 Enzyme ◽  
Acute Alcoholic Pancreatitis ◽  
Acute And Chronic Pancreatitis

In both developed and developing countries, overuse of alcohol is a considered as the major cause of acute and chronic pancreatitis. Prolonged overconsumption of alcohol for 5–10 years typically precedes the initial attack of acute alcoholic pancreatitis. It is observed that only a minority (around 5%) of alcoholics develop pancreatitis. It is now established that the pancreas has the capacity to metabolize ethanol. Previous studies have shown that there are two major pathways of ethanol metabolism, oxidative and non-oxidative. Oxidative ethanol metabolism involves the conversion of ethanol to acetaldehyde, a reaction that is catalysed by aldehyde dehydrogenase (ADH) with contributions from cytochrome P450 enzyme (CYP2E1) and possibly also catalase. Genetic factors regulating alcohol metabolism could predispose in developing alcoholic pancreatitis (AP). We investigated the association of polymorphisms in ADH enzymes with the alcoholic pancreatitis in North coastal Andhra Pradesh. Patients with alcoholic pancreatitis (AP; n = 100), alcoholic controls (AC; n = 100), and healthy controls (HC; n = 100) were included in the study. Blood samples were collected from the subjects in EDTA coated vials. DNA was extracted and genotyping for ADH2 and ADH3 was done by PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism). The products were analysed by gel electrophoresis. The frequency distribution of ADH3*1/*1 genotype was significantly higher in AP group (54%) compared with AC (35%), and HC (42%), and was found to be associated with increased risk of alcoholic pancreatitis. There was no statistically significant difference between the frequency distribution of ADH3*1/*1, ADH3*1/*2, and ADH3*2/*2 genotypes between AC and HC. There was no statistically significant difference between the frequency distribution of ADH2*1/*1, ADH2*1/*2, and ADH2*2/*2 genotypes in AP compared with AC and HC. This study shows that carriers of ADH3*1/*1 individuals consuming alcohol are at higher risk for alcoholic pancreatitis than those with other genotypes such as ADH3*1/*2 and ADH3*2/*2. 

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