Immune system - drug metabolism interactions: Toxicological insight

Yanev, S.

doi:10.14748/adipo.v6.1133

Cited by 4 publications

(3 citation statements)

References 52 publications

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“…When a foreign body is detected, the innate immune response releases AMPs and initiates the neuroin ammation process [50]. This in ammatory mechanism works in tandem with the downregulation of the main xenobiotic metabolising CYP enzyme system [51]. In an APP23 mouse AD model, the inhibition of Cyp46a1 expression was followed by an abundance of Aβ peptides, which caused a build-up of brain cholesterol and eventual neuronal death [52].…”

Section: Discussionmentioning

confidence: 99%

Behavioural Effects and RNA-seq Analysis of Aβ42-Mediated Toxicity in a Drosophila Alzheimer’s Disease Model

et al. 2023

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Alzheimer's disease (AD) is the most common neurological ailment worldwide. Its process comprises the unique aggregation of extracellular senile plaques composed of amyloid-beta (Aβ) in the brain. Aβ42 is the most neurotoxic and aggressive of the Aβ42 isomers released in the brain. Despite much research on AD, the complete pathophysiology of this disease remains unknown. Technical and ethical constraints place limits on experiments utilizing human subjects. Thus, animal models were used to replicate human diseases as a result. The Drosophila melanogaster is an excellent model for studying both physiological and behavioural aspects of human neurodegenerative illnesses. Here, the negative effects of Aβ42-expression on a Drosophila AD model were investigated through three behavioural assays followed by RNA-seq. The RNA-seq data was veri ed using qPCR. AD Drosophila expressing human Aβ42 exhibited degenerated eye structures, shortened lifespan and declined mobility function compared to the wild-type Control. RNAseq revealed 1496 genes that were differentially expressed from the Aβ42-expressing samples against the Control. Among the pathways that were identi ed from the differentially expressed genes include carbon metabolism, oxidative phosphorylation, antimicrobial peptides and longevity regulating pathways. While AD is a complicated neurological condition whose aetiology is in uenced by a number of factors, it is hoped that the current data will be su cient to give a general picture of how Aβ42 in uences the disease pathology. The discovery of molecular connections from the current Drosophila AD model offers fresh perspectives on the usage of this Drosophila which could aid in the discovery of new anti-AD medications. HighlightsAβ42 expression in the Drosophila eye resulted in severe rough eye phenotype.Drosophila melanogaster expressing Aβ42 exhibited shortened lifespan.Aβ42-expressing Drosophila melanogaster had impaired climbing abilities.From the RNA-seq analysis, AD samples showed 1496 DEGs compared to Control.

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Section: Discussionmentioning

confidence: 99%

Behavioural Effects and RNA-seq Analysis of Aβ42-Mediated Toxicity in a Drosophila Alzheimer’s Disease Model

et al. 2023

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“…The source of modulation of CYP enzymes’ activities is endogenous inflammation markers: cytokines, adipokines, lipid metabolites of nitric oxide, proteases, and reactive oxygen species [ 132 ]. Inflammation is accompanied by suppression of the CYP enzymes that metabolize xenobiotics, including medical drugs [ 393 ]. The most studied CYP subfamily in inflammation is CYP3A [ 390 ].…”

Section: Cyp3a Involvement In Pathological Processesmentioning

confidence: 99%

The Role of CYP3A in Health and Disease

2022

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CYP3A is an enzyme subfamily in the cytochrome P450 (CYP) superfamily and includes isoforms CYP3A4, CYP3A5, CYP3A7, and CYP3A43. CYP3A enzymes are indiscriminate toward substrates and are unique in that these enzymes metabolize both endogenous compounds and diverse xenobiotics (including drugs); almost the only common characteristic of these compounds is lipophilicity and a relatively large molecular weight. CYP3A enzymes are widely expressed in human organs and tissues, and consequences of these enzymes’ activities play a major role both in normal regulation of physiological levels of endogenous compounds and in various pathological conditions. This review addresses these aspects of regulation of CYP3A enzymes under physiological conditions and their involvement in the initiation and progression of diseases.

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“…Inflammation is associated with an activation of the immune system characterized by release of cytokines, adipokines, lipid metabolites nitric oxide, proteases, and reactive oxygen species. The above inflammation mechanism comes along with the downregulation of the main xenobiotic/drug metabolizing CYP enzyme system (Figure 1 ) both in the liver and in the adipose tissue ( 7 ).…”

Section: In Light Of the Inflammation Mechanismmentioning

confidence: 99%

The Role of Cytochromes P450 in Infection

2018

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Cytochromes are expressed in many different tissues of the human body. They are found mostly in intestinal and hepatic tissues. Cytochromes P450 (CYPs) are enzymes that oxidize substances using iron and are able to metabolize a large variety of xenobiotic substances. CYP enzymes are linked to a wide array of reactions including and O-dealkylation, S-oxidation, epoxidation, and hydroxylation. The activity of the typical P450 cytochrome is influenced by a variety of factors, such as genus, environment, disease state, herbicide, alcohol, and herbal medications. However, diet seems to play a major role. The mechanisms of action of dietary chemicals, macro- and micronutrients on specific CYP isoenzymes have been extensively studied. Dietary modulation has effects upon the metabolism of xenobiotics. Cytochromes harbor intra- or interindividual and intra- or interethnic genetic polymorphisms. Bacteria were shown to express CYP-like genes. The tremendous metabolic activity of the microbiota is associated to its abundant pool of CYP enzymes, which catalyze phase I and II reactions in drug metabolism. Disease states, intestinal disturbances, aging, environmental toxic effects, chemical exposures or nutrition modulate the microbial metabolism of a drug before absorption. A plethora of effects exhibited by most of CYP enzymes can resemble those of proinflammatory cytokines and IFNs. Moreover, they are involved in the initiation and persistence of pathologic pain by directly activating sensory neurons and inflammatory cytokines.

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Immune system - drug metabolism interactions: Toxicological insight

Cited by 4 publications

References 52 publications

Behavioural Effects and RNA-seq Analysis of Aβ42-Mediated Toxicity in a Drosophila Alzheimer’s Disease Model

Behavioural Effects and RNA-seq Analysis of Aβ42-Mediated Toxicity in a Drosophila Alzheimer’s Disease Model

The Role of CYP3A in Health and Disease

The Role of Cytochromes P450 in Infection

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