{
  "abstract": "Introduction Sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly empagliflozin (EMPA), have demonstrated anti-inflammatory and antifibrotic effects through inhibition of TGF- β signaling pathways. This pilot study aimed to investigate the effects of EMPA on bleomycin-induced skin fibrosis and to compare two different administration routes—oral gavage and drinking water.Material and Methods Eight female Wistar albino rats (6–8 weeks, 200–250 g) were randomly assigned into two groups: healthy controls (n=2) and bleomycin-induced disease model (n=6).The disease group was divided into three subgroups: placebo (n=2), EMPA by oral gavage (n=2), and EMPA by drinking water (n=2).Skin fibrosis was induced by subcutaneous bleomycin injections (10 mg/kg, 1 mg/ml) on alternate weekdays for four weeks; controls received NaCl using the same schedule. EMPA treatment was initiated at week 3 (10 mg/kg/day, 5 days per week). Weekly ultrasound imaging (4–20 MHz) was performed bilaterally on the dorsal region.Radiological skin thickness (epidermis+dermis) was measured at three points and then averaged.Skin biopsies were collected at week 4. Hematoxylin–eosin was used for general evaluation, Masson trichrome for collagen deposition, α-SMA for myofibroblasts, and CD3 for T-lymphocyte and CD20 for B-lymphocyte infiltration.Inflammation and collagen scores were semiquantitatively graded (0–3).Skin thickness was measured at three sites on each pathology slide, spanning the epidermis and dermis.Results Pathological skin thickness was 0.93 ± 0.10 mm in healthy controls, 1.50 ± 0.25 mm in disease controls, and 1.32 ± 0.30 mm in EMPA-treated rats (p1<0.001). T-lymphocyte count was significantly lower in the treatment group (3.69 ± 1.08) compared with disease controls (5.38 ± 1.06) and healthy controls (3.13 ± 0.84; p1 =0.002).B-lymphocyte and eosinophil counts were also significantly reduced in EMPA-treated animals versus disease controls (p1 =0.004 and p1 =0.001, respectively). The inflammatory response score was 0.13 ± 0.35 in healthy controls, 1.00 in disease controls, and 0.31 ± 0.48 in the EMPA group (p1 <0.001). Collagen homogenization scores were 0.38 ± 0.52, 2.00, and 1.69 ± 0.48, respectively (p1 <0.001). Myofibroblast counts were highest in the EMPA group (p1 <0.001). Radiological skin thickness decreased significantly by week 3 in EMPA-treated rats compared with both disease and healthy controls (p1 <0.001).While pathological assessments showed comparable outcomes between the two EMPA administration routes, radiological findings favored the oral gavage method ( table 1, p3).Conclusions In a bleomycin-induced scleroderma model, EMPA reduced skin thickness, inflammatory infiltration, and collagen deposition regardless of administration route.These findings suggest that EMPA exerts antifibrotic and anti-inflammatory effects and may represent a potential therapeutic option for systemic sclerosis.Abstract P.275 Figure 1A-C) High-frequency ultrasound images illustrating skin thickness measurements in the dorsal region of rats. D-E) Temporal changes in radiological skin thicknessAbstract P.275 Table 1Comparison of pathological findings and radiological skin thickness measurements among groups",
  "authors": [
    {
      "affiliations": [
        "Department of Internal Medicine, Kocaeli University Faculty of Medicine, Kocaeli, Turkey"
      ],
      "name": "Seyma Yilmaz"
    },
    {
      "affiliations": [
        "Department of Pathology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey"
      ],
      "name": "Seda Duman Ozturk"
    },
    {
      "affiliations": [
        "Experimental Medicine Research Unit (DETAB), Kocaeli, Turkey"
      ],
      "name": "Cuneyt Ozer"
    },
    {
      "affiliations": [
        "Department of Radiology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey"
      ],
      "name": "Ozgur Cakir"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Internal Medicine, Kocaeli University Faculty of Medicine, Kocaeli, Turkey"
      ],
      "name": "Andac Komac"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Internal Medicine, Kocaeli University Faculty of Medicine, Kocaeli, Turkey"
      ],
      "name": "Ayten Yazici"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Internal Medicine, Kocaeli University Faculty of Medicine, Kocaeli, Turkey"
      ],
      "name": "Ayse Cefle"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Internal Medicine, Kocaeli University Faculty of Medicine, Kocaeli, Turkey"
      ],
      "name": "Duygu Temiz Karadag"
    }
  ],
  "title": "P.275 The effect of empagliflozin on skin fibrosis in a bleomycin-induced scleroderma model and comparison of different routes of administration",
  "uid": "cdd92c3b-d582-52a6-8388-025efe0bc361"
}