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.

scholarly journals Effects of Diet and Phytogenic Inclusion on the Antioxidant Capacity of the Broiler Chicken Gut

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 739
Author(s):  
Eirini Griela ◽  
Vasileios Paraskeuas ◽  
Konstantinos C. Mountzouris
Keyword(s):  
Antioxidant Capacity ◽  
Antioxidant Response ◽  
Feed Additives ◽  
Poultry Production ◽  
Gut Health ◽  
Gene Expressions ◽  
Protein Levels ◽  
Study Results ◽  
Total Antioxidant ◽  
Diet Type

The reduction in energy and protein dietary levels, whilst preserving the gut health of broilers, is warranted in modern poultry production. Phytogenic feed additives (PFAs) are purported to enhance performance and antioxidant capacity in broilers. However, few studies have assessed PFA effects on a molecular level related to antioxidant response. The aim of this study was to investigate the effects of administering two dietary types differing in energy and protein levels (L: 95% and H: 100% of hybrid optimal recommendations) supplemented with or without PFA (−, +) on gene expressions relevant for antioxidant response along the broiler gut. Interactions of diet type with PFA (i.e., treatments L−, L+, H−, H+) were determined for critical antioxidant and cyto-protective genes (i.e., nuclear factor erythroid 2-like 2 (Nrf2) pathway) and for the total antioxidant capacity (TAC) in the proximal gut. In particular, the overall antioxidant response along the broiler gut was increased upon reduced dietary energy and protein intake (diet type L) and consistently up-regulated by PFA addition. The study results provide a new mechanistic insight of diet and PFA functions with respect to the overall broiler gut antioxidant capacity.

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 Phytogenic Compounds for Enhancing Intestinal Barrier Function in Poultry–A Review

Planta Medica ◽  
2021 ◽  
Author(s):  
Urszula Latek ◽  
Magdalena Chłopecka ◽  
Wojciech Karlik ◽  
Marta Mendel
Keyword(s):  
Barrier Function ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Feed Additives ◽  
Intestinal Barrier Function ◽  
Poultry Production ◽  
Gut Health ◽  
Growth Promoters ◽  
Gut Barrier Function ◽  
Antibiotic Growth Promoters

AbstractAfter the European Union ban of antibiotic growth promoters, works on different methods of improving gut health have intensified. The poultry industry is struggling with problems that were previously controlled by antibiotic growth promoters, therefore the search for optimal solutions continues. Simultaneously, there is also increasing social pressure to minimize the use of antibiotics and replace them with alternative feed additives. A variety of available alternatives is considered safe by consumers, among which phytogenics play a significant role. However, there are still some limitations that need to be considered. The most questionable are the issues related to bioavailability, metabolism of plant derivatives in birds, and the difficulty of standardizing commercial products. There is still a need for more evidence-based recommendations for the use of phytogenics in livestock. On the other hand, a positive influence of phytogenic compounds on the health of poultry has been previously described by many researchers and practical application of these compounds has auspicious perspectives in poultry production. Supplementation with phytogenic feed additives has been shown to protect birds from various environmental threats leading to impaired intestinal barrier function. Phytogenic feed additives have the potential to improve the overall structure of intestinal mucosa as well as gut barrier function on a molecular level. Recognition of the phytogenicsʼ effect on the components of the intestinal barrier may enable the selection of the most suitable ones to alleviate negative effects of different agents. This review aims to summarize current knowledge of the influence of various phytogenic constituents on the intestinal barrier and health of poultry.

scholarly journals Reconstitution of theIn VitroActivity of the Cyclosporine-Specific P450 Hydroxylase from Sebekia benihana and Development of a Heterologous Whole-Cell Biotransformation System

2015 ◽  
Vol 81 (18) ◽  
pp. 6268-6275 ◽  
Author(s):  
Li Ma ◽  
Lei Du ◽  
Hui Chen ◽  
Yue Sun ◽  
Shan Huang ◽  
...  
Keyword(s):  
Redox System ◽  
Cytochrome P450 Enzyme ◽  
Regeneration System ◽  
Nadph Regeneration ◽  
Site Specific ◽  
Whole Cell ◽  
Content Type ◽  
P450 Enzyme

ABSTRACTThe cytochrome P450 enzyme CYP-sb21 fromSebekia benihanais capable of catalyzing the site-specific hydroxylation of the immunosuppressant cyclosporine (CsA), leading to the single product γ-hydroxy-N-methyl-l-Leu4-CsA (CsA-4-OH). Unlike authentic CsA, this hydroxylated CsA shows significantly reduced immunosuppressive activity while it retains a side effect of CsA, the hair growth stimulation effect. Although CYP-sb21 was previously identified to be responsible for CsA-specific hydroxylationin vivo, thein vitroactivity of CYP-sb21 has yet to be established for a deeper understanding of this P450 enzyme and further reaction optimization. In this study, we reconstituted thein vitroactivity of CYP-sb21 by using surrogate redox partner proteins of bacterial and cyanobacterial origins. The highest CsA site-specific hydroxylation activity by CYP-sb21 was observed when it was partnered with the cyanobacterial redox system composed ofseFdx andseFdR fromSynechococcus elongatusPCC 7942. The best bioconversion yields were obtained in the presence of 10% methanol as a cosolvent and an NADPH regeneration system. A heterologous whole-cell biocatalyst usingEscherichia coliwas also constructed, and the permeability problem was solved by usingN-cetyl-N,N,N-trimethylammonium bromide (CTAB). This work provides a useful example for reconstituting a hybrid P450 system and developing it into a promising biocatalyst for industrial application.

Pharmacogenetics of the hepatic cytochrome P450 enzyme system: its relevance for prescribing in psychiatry

1998 ◽  
Vol 15 (3) ◽  
pp. 96-99
Author(s):  
Alan O'Donohoe ◽  
Michael Gill
Keyword(s):  
Genetic Variation ◽  
Cytochrome P450 ◽  
Current Knowledge ◽  
Enzyme System ◽  
Genetic Influences ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
P450 Enzyme ◽  
Cytochrome P450 Enzyme System ◽  
Hepatic Cytochrome

AbstractThis article reviews the current knowledge regarding the hepatic cytochrome P450 system, with particular reference to its effect on psychotherapeutic medication. The metabolic processes – by which drugs are broken down in the liver by cytochrome P450 enzymes – are affected by genetic variation between individuals, inhibition and induction of these enzymes by other drugs, disease and age. Genetic influences and enzyme inhibition/induction are discussed in particular detail in this article.

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.

scholarly journals Knowledge, Attitude, and Practices on Antimicrobial Use and Antimicrobial Resistance among Poultry Drug and Feed Sellers in Bangladesh

2021 ◽  
Vol 8 (6) ◽  
pp. 111
Author(s):  
Md. Abul Kalam ◽  
Md. Abdul Alim ◽  
Shahanaj Shano ◽  
Md. Raihan Khan Nayem ◽  
Md. Rahim Badsha ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Current Knowledge ◽  
Rank Order ◽  
Antimicrobial Use ◽  
Poultry Production ◽  
Attitudes And Practices ◽  
12Th Grade ◽  
Study Results ◽  
Knowledge Attitudes And Practices ◽  
Drug Sellers

Poultry production has boomed in Bangladesh in recent years. The poultry sector has contributed significantly to meet the increased demand for animal source proteins in the country. However, increased use of antimicrobials and antibiotics appeared to be a significant threat to food safety in the poultry sector. The poultry drug and feed sellers are at the frontline position involving selecting and delivering the antimicrobials to the poultry farmers. Studies assessing the poultry drug and feed sellers’ knowledge, attitudes, and practices (KAPs) are limited. The current study aimed to assess the community poultry drug and feed sellers’ KAPs of antimicrobial use (AMU) and antimicrobial resistance (AMR) in some selected areas of Bangladesh. We determined the respondents’ (drug and the feed sellers) KAPs of AMU and AMR using a tested and paper-based questionnaire. The study demonstrated that most respondents have insufficient knowledge, less positive attitudes, and inappropriate practices regarding AMU and AMR. The factor score analysis further showed that the type of respondents and their years of experience, level of education, and training on the drug were the significant factors impacting the current knowledge, attitudes, and practices of AMU and AMR. The adjusted logistic regression analysis revealed that the drug sellers who completed their education up to 12th grade and had training on the drug had adequate knowledge of AMU and AMR. The data also showed that the drug sellers belong to the age group 31–35 and 36–40 years and who completed 12th grade had good attitudes on the same. Likewise, the analysis further determined that drug sellers belonging the age category 18–25 and 26–30 years, and interestingly, the respondents who completed education up to 12th grade, had better practices. Spearman’s rank-order correlation revealed a positive association between each pair of the KAPs scores for the respondents. The correlation was fair between knowledge–attitudes, knowledge–practices, and attitudes–practices. Based on the current study results, we recommend educational interventions and appropriate training for the poultry drug and feed sellers to raise awareness and to upgrade their current knowledge on the appropriate use of antimicrobials. This will ultimately lead to reducing the chances of developing AMR in the poultry sectors of the country.

Sign in / Sign up

Export Citation Format

Share Document