Involvement of cytochrome P450 enzymes in inflammation and cancer: a review

Stipp, Maria Carolina; Acco, Alexandra

doi:10.1007/s00280-020-04181-2

Cited by 70 publications

(48 citation statements)

References 109 publications

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“…Moreover, the hypomethylation levels were higher in stable MHO. CYP2E1 belongs to the superfamily of enzymes, cytochrome P450 (CYP), whose members are involved in the biotransformation of drugs, xenobiotics and endogenous substances [ 32 ]. The increased activity of CYP2E1 may promote oxidative stress due to its ability to produce excessive reactive oxygen species [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study

Gutiérrez-Repiso

Linares-Pineda

González-Jiménez

et al. 2021

IJMS

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Background: Identifying those parameters that could potentially predict the deterioration of metabolically healthy phenotype is a matter of debate. In this field, epigenetics, in particular DNA methylation deserves special attention. Results: The aim of the present study was to analyze the long-term evolution of methylation patterns in a subset of metabolically healthy subjects in order to search for epigenetic markers that could predict the progression to an unhealthy state. Twenty-six CpG sites were significantly differentially methylated, both at baseline and 11-year follow-up. These sites were related to 19 genes or pseudogenes; a more in-depth analysis of the methylation sites of these genes showed that CYP2E1 had 50% of the collected CpG sites differently methylated between stable metabolically healthy obesity (MHO) and unstable MHO, followed by HLA-DRB1 (33%), ZBTB45 (16%), HOOK3 (14%), PLCZ1 (14%), SLC1A1 (12%), MUC2 (12%), ZFPM2 (12.5%) and HLA-DQB2 (8%). Pathway analysis of the selected 26 CpG sites showed enrichment in pathways linked to th1 and th2 activation, antigen presentation, allograft rejection signals and metabolic processes. Higher methylation levels in the cg20707527 (ZFPM2) could have a protective effect against the progression to unstable MHO (OR: 0.21, 95%CI (0.067–0.667), p < 0.0001), whilst higher methylation levels in cg11445109 (CYP2E1) would increase the progression to MUO; OR: 2.72, 95%CI (1.094–6.796), p < 0.0014; respectively). Conclusions: DNA methylation status is associated with the stability/worsening of MHO phenotype. Two potential biomarkers of the transition to an unhealthy state were identified and deserve further investigation (cg20707527 and cg11445109). Moreover, the described differences in methylation could alter immune system-related pathways, highlighting these pathways as therapeutic targets to prevent metabolic deterioration in MHO patients.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study

Gutiérrez-Repiso

Linares-Pineda

González-Jiménez

et al. 2021

IJMS

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“…A second realm of strong biomedical interest is the role of CYPs in the metabolism of antitumor agents. CYPs have been detected in tumors, as well as cancer cells and cell lines [ 19 , 20 ]. Most antitumor agents that exert antitumor efficacy in cancer cells have been observed to be metabolized by the CYP1, CYP2, and CYP3 family, such as flavonoids by CYP1b1, tamoxifen by CYP2D6, docetaxel and cyclophosphamide by CYP3A4/5, thalidomide by CYP2C9 and CYP2C19, and paclitaxel by CYP2C8 [ 21 , 22 ].…”

Section: Human Cypsmentioning

confidence: 99%

Cytochrome P450 Enzymes and Drug Metabolism in Humans

Zhao

Ma²,

et al. 2021

IJMS

352

147

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Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1–3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.

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“…Hepatotoxicity sign caused by chemical is important in human health and drug industry and this acute liver damage sign is resulting by increasing level of specific enzyme [13,14]. M showed the lowest acute liver damage probability while AI was the highest with 0.85 Table (4) and Figure (6).…”

Section: Resultsmentioning

confidence: 99%

In Silico Taste, Cytochrome and Toxicity Prediction Study of Major Chamomile Constituents

Hammud¹

2021

IJOIR

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Chamomile is an ancient herb used for various medications. It contains many bioactive constituents such as volatile oils, terpenoids, flavonoids, lactones, acid esters, glycosides and others. By reviewing many references, a confliction appeared of using Chamomile preparations to treat primary teeth eruption symptoms as a therapy administered by pediatric dentist or pediatrician. In this study, thirteen bioactive constituents (α-bisabolol (B), chamazulene (C), umbelliferone (U), apigenin (A), apigetrin (AT), apiin (AI), luteolin (L), quercetin (Q), quercimertrin (QT), rutin (R), α-cadinene (CD), α-farnesene (F), and matricarin (M) were subject to computational predication through various online websites to predicate their taste, activity towards several CYP450 enzymes and their action as Hepatotoxic, carcinogenic, immunotoxic, mutagenic, and cytotoxic compounds. Our calculations revealed several points such as high value of taste predication indicated that Chamomile constituents under study were with sour taste, did not classify as individual fatal compound Class (GHS) 1 or 2, 44.87% of them showed inhibition character toward specific cytochrome P450 enzyme while 43.59% were non- inhibition character, more than (0.5) probability predication of various cytochrome P450 enzymes gave a positive activity that may affect liver functions. Also, hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity predictions were more than (0.5), unsaturated Chamomile constituent (Farnesene, F) had highest immune – and mutagenic properties whilst the disaccharide flavonoid (Rutin, R) had the highest Carcino- immunogenic response. According to the above notes, our conclusion is to use minimum concentration of Chamomile preparation for less period of time and lowest repeating intake that ensure effective treatment of teething symptoms under supervision of pediatricians with minimum side effect.

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Involvement of cytochrome P450 enzymes in inflammation and cancer: a review

Cited by 70 publications

References 109 publications

Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study

Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study

Cytochrome P450 Enzymes and Drug Metabolism in Humans

In Silico Taste, Cytochrome and Toxicity Prediction Study of Major Chamomile Constituents

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