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.

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.

Drug distribution and elimination in anaesthetic practice

2017 ◽  
Author(s):  
Eveline L. A. van Dorp ◽  
Douglas Eleveld ◽  
Erik Olofsen ◽  
Jaap Vuyk
Keyword(s):  
Blood Flow ◽  
Enzyme Activity ◽  
Protein Binding ◽  
Drug Distribution ◽  
Hepatic Clearance ◽  
Drug Clearance ◽  
The Body ◽  
Cytochrome P450 Enzyme ◽  
Anaesthetic Agents ◽  
P450 Enzyme

An understanding of pharmacokinetics is vital for the practice of anaesthesia. Drugs are, after administration, distributed throughout the body to the effect site (mostly the brain) to exert their effects. This can be influenced by differences in protein binding, systemic blood flow, and concomitant medication. Elimination of drugs from the body is through two main routes: either unchanged through the kidneys or through metabolism by the liver (and consecutive excretion through the kidneys). This process depends on the amount of hepatic blood flow and the amount of hepatic extraction. This in turn depends on the amount of protein binding and the intrinsic hepatic clearance. The cytochrome P450 enzyme family also plays an important role in drug elimination. Individual differences in enzyme activity can lead to differences in drug effect and clearances. Changes in enzyme activity by enzyme induction and inhibition can also be of influence on drug clearance. Compartmental, non-compartmental, and physiologically based models, and various statistical approaches to estimate these models, may be used to analyze the distribution and elimination of anaesthetic agents.

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.

Mechanisms and practical use of the bactericidal effects of ozone and ozonated oils

2020 ◽  
pp. 45-52
Author(s):  
S. Schetinin
Keyword(s):  
Inflammatory Diseases ◽  
Aerobic Metabolism ◽  
Active Oxygen ◽  
The Body ◽  
Bactericidal Action ◽  
Ozone Therapy ◽  
Energy Substrates ◽  
Bactericidal Effects ◽  
Viral Nature

The analysis of the clinical and immunological effectiveness of ozone therapy is carried out. The mechanism of the bactericidal action of ozone in the treatment of infectious and inflammatory diseases of a bacterial and viral nature is analyzed. Ozonation of oils leads to the formation of a complex and heterogeneous cascade of components. Ozonides provide the body with some prolonged supply of active oxygen to maintain aerobic metabolism and the required level of energy substrates.

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. 

scholarly journals Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

2021 ◽  
Author(s):  
E. Heinonen ◽  
M. Blennow ◽  
M. Blomdahl-Wetterholm ◽  
M. Hovstadius ◽  
J. Nasiell ◽  
...  
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Plasma Concentrations ◽  
Relative Difference ◽  
Interindividual Variation ◽  
Therapeutic Drug ◽  
Cytochrome P450 Enzyme ◽  
Second Trimester ◽  
P450 Enzyme ◽  
Placental Passage

Abstract Purpose Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. Method Pregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. Results Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. Conclusion Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. Trial registration The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

The role of cytochrome P450 enzyme genetic variants in cannabis hyperemesis syndrome—A case report

2021 ◽  
Author(s):  
Maxim Kuzin ◽  
Franziskos Xepapadakos ◽  
Isabel Scharrer ◽  
Marc Augsburger ◽  
Chin‐Bin Eap ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Case Report ◽  
Genetic Variants ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme ◽  
Cannabis Hyperemesis Syndrome

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

Sign in / Sign up

Export Citation Format

Share Document