Preliminary exploration of ferroptosis induced by three chemical inducers in atopic dermatitis-like mouse model
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1.Shenzhen Center for Chronic Disease Control, Shenzhen Insititute of Dermatology;2.Shenzhen Center for Chronic Disease Control, Shenzhen Insititute of Dermatology,School of Public Health.Guangdong Medical University;3.Shenzhen Center for Chronic Disease Control,Shenzhen Insititute of Dermatology

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    Abstract:

    【Abstract】 Objective?To establish atopic dermatitis (AD)-like models in BALB/c mice using three chemical inducers, calcipotriol (MC903), 2,4-dinitrochlorobenzene (DNCB)and oxazolone (OXA). Preliminarily explore the ferroptosis in different mice models.?Methods?Healthy 7-week-old female BALB/c mice were randomly divided into 8 groups (n=8 per group) based on induction sites (ears/dorsal skin): Control ear/dorsal groups, MC903 ear/dorsal groups, DNCB ear/dorsal groups, and OXA ear/dorsal groups. Model establishment involved topical application of respective agents at specified concentrations. MC903 ear/dorsal groups underwent continuous induction for 14 days. DNCB and OXA ear/dorsal groups sensitized for 3 consecutive days, and on day8, these mice were challenged 12 times every other day for up to 30 days. The skin lesions of mice were observed, the thickness of the skin was measured, the levels of ROS, IL-4, IFN-γ and MDA in the plasma were detected, the histopathological staining and ultrastructural observation of the skin were carried out, and the expression of ferroptosis-related proteins(GPX4, FTH1, ACSL4, TfR1) was detected by Western blot.Results Compared with controls, all models exhibited obvious redness and swelling, scratching and desquamation, and rough thickening of the skin,and skin thickness was significantly increased(P<0.01).ROS, IFN-γ,IL-4 and MDA levels were also elevated to varying extents (P<0.05).Histopathological features including epidermal hyperplasia, keratinocyte degeneration, dermal vascular congestion, and immune cell infiltration .TEM evidence showed mitochondrial membrane rupture, increased density, cristae reduction.Dysregulated ferroptosis markers: Significantly decreased GPX4/FTH1 and increased ACSL4/TfR1 expression(P<0.05). Conclusions All three chemicals successfully induced AD-like phenotypes in BALB/c mice through site-specific applications. Ferroptosis is involved in AD pathological process, but heterogeneity exists across different inducer induction methods and modeling sites.

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History
  • Received:March 27,2025
  • Revised:September 01,2025
  • Adopted:September 05,2025
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