Dataset Information

Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne.

ABSTRACT: Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. This study aimed to explore the pathogenesis of acne and the therapeutic mechanism of isotretinoin from the metabolic perspective in coal tar-induced acne in rabbits. Methods: Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was used to identify skin metabolites in groups C (blank control), M (model group) and T (isotretinoin group). Multivariate statistical analysis was used to process the metabolomics data. Results: 98 differential metabolites in group C and group M were identified. The highest proportion of differential metabolites were organic acids and derivatives, lipid metabolites, organic heterocyclic compounds, and nucleoside metabolites. The most significant metabolic pathways included protein digestion and absorption, central carbon metabolism in cancer, ABC transporters, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, and sphingolipid signaling pathway. Isotretinoin treatment normalized eight of these metabolites. Conclusions: Our study will help to further elucidate the pathogenesis of acne, the mechanism of isotretinoin at the metabolite level, and identify new therapeutic targets for treating acne.

SUBMITTER: Ou-Yang XL

PROVIDER: S-EPMC9470959 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne.

Ou-Yang Xiao-Liang XL Zhang Deng D Wang Xiu-Ping XP Yu Si-Min SM Xiao Zhen Z Li Wei W Li Chun-Ming CM

Frontiers in pharmacology 20220831

<b>Background:</b> Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. This study aimed to explore the pathogenesis of acne and the therapeutic mechanism of isotretinoin from the metabolic perspective in coal tar-induced acne in rabbits. <b>Methods:</b> Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was used to identify skin metabolites in groups C (blank control), M (model group) and T (isotretin ...[more]

PMID: 36120319

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Project description:Emergence and potential transfer of antibiotic resistance in skin microorganisms is of current concern in medicine especially in dermatology contexts where long term treatment with antibiotics is common. Remarkably, non-antibiotic therapy in the form of isotretinoin - a non-antimicrobial retinoid is effective at reducing or eradicating the anaerobe Propionibacterium acnes which is causally involved in the complex pathogenesis of Acne vulgaris. This study measured the extent of colonization of P. acnes in patients with primary cystic or severe acne from three defined skin sites in 'non-lesion' areas before, during and after treatment with isotretinoin. Patients attending acne clinics were investigated using standardized skin sampling techniques and the recovery of anaerobic P. acnes from 56 patients comprising 24 females and 32 males (mean age 22 years, age range 15-46 years) who were given a standard course of isotretinoin (1 mg/kg/day) are reported. P. acnes cultured from the external cheek surface of patients following treatment showed a significant reduction (1-2 orders of magnitude) compared with their pre-treatment status. Interestingly, other distinct sites (nares and toe web) failed to show this reduction. In addition, high levels of antibiotic-resistant P. acnes were recorded in each patients' skin microbiota before, during and after treatment. In this study, microbial composition of the skin appears substantially altered by isotretinoin treatment, which clearly has differential antimicrobial effects on each anatomically distinct site. Our study confirmed that orally administered isotretinoin shows good efficacy in the resolution of moderate to severe acne that correlates with reductions in the number of P. acnes on the skin, including resistant isolates potentially acquired from previous treatments with antibiotics. Our study suggests that the role of tetracycline's and macrolides, which are currently first line treatments in dermatology, might be reserved for severe or life-threatening infections since current antibiotic stewardship guidelines from medical departments no longer prescribe these antibiotics for routine use.

Project description:ObjectivesTo identify what changes in the prescribing of isotretinoin have occurred since funded prescriber access was widened in 2009 from 'dermatologist only' prescribing to include 'general practitioners (GPs) and nurse practitioners working within their scope of practice'.DesignEvaluation of isotretinoin dispensing data from 2008 to 2023 using the national annual prescribing data obtained from the New Zealand Pharmaceutical National Collection database.SettingAll New Zealand citizens prescribed and dispensed funded isotretinoin for acne from 2008 to 2023 were included.Main outcome measuresThe prescribing data were analysed to identify the total number of prescriptions per year by prescribing clinician type, patient ethnicity and deprivation levels.ResultsIn 2008, nearly 100% (26 897) of dispensed prescriptions were written by a dermatologist, while in 2023, 79% (39 432) were written by primary care clinicians. Annual isotretinoin prescriptions increased by 87%, from 26 897 (2008) to 50 613 (2023). Prescriptions for Māori increased from 1750 in 2008 to 4374 in 2023, with similar increases for other ethnic minorities.ConclusionExpanding the prescriber cohort has resulted in a substantial increase in prescriptions, with primary care now issuing the majority of isotretinoin prescriptions. These data demonstrate that the GP workforce can absorb and manage the additional acne workload from the increasing population. Enhanced access for patients suggests an unmet need. An absolute number of prescriptions have risen faster for Māori and Asian patients than for Europeans. Pacific people were generally lower than Europeans. This suggests the longstanding ethnic disparity in access to isotretinoin is partially reduced.Many countries have restrictions on patient access to isotretinoin, similar to New Zealand in 2008. This is the first study demonstrating that, given appropriate postgraduate education and support, the isotretinoin risk-benefit profile may be enhanced to safely deliver high-quality, timely, equitable patient access to isotretinoin in primary care.

Dataset Information

Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne.

Publications

Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne.

Similar Datasets

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