کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8530941 | 1559728 | 2018 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Neutrophils contribute to the pathogenesis of hemorrhagic cystitis induced by ifosfamide
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
Ifosfamide (IFO) is an antineoplastic drug that is commonly used to treat gynecological and breast cancers. Hemorrhagic cystitis (HC) is a common side effect associated with IFO injection, which courses with neutrophil accumulation and affects 6-50% of patients depending on dose intensity. Here, we investigated the role of neutrophils in this inflammatory process. Female Swiss mice (nâ¯=â¯8/group) were injected with saline, IFO (400â¯mg/kg, i.p.), fucoidan (a P- and L-selectins inhibitor, 100â¯mg/kg, i.v.) or IFOâ¯+â¯fucoidan (1-100â¯mg/kg) alone or combined with mesna (80â¯mg/kg i.p.). Another group of mice received anti-Ly6G antibody (500â¯Î¼g/mouse, once daily for 2â¯days) for neutrophil depletion before IFO injection. In another experimental setting, animals received granulocyte colony-stimulating factor (G-CSF, 400â¯Î¼g/kg), IFO (200â¯mg/kg), G-CSF (25-400â¯Î¼g/kg, for 5â¯days)â¯+â¯IFO (200â¯mg/kg, i.p.) or fucoidanâ¯+â¯G-CSFâ¯+â¯IFO. Bladder injury was evaluated 12â¯h after IFO injection. IFO 400â¯mg/kg significantly increased visceral hyperalgesia, bladder edema, hemorrhage, vascular permeability, MPO, IL-1β and IL-6 tissue levels, and COX-2 immunostaining and expression versus the saline group (Pâ¯<â¯0.05). Conversely, fucoidan (100â¯mg/kg) significantly attenuated these parameters compared to IFO-injected mice (Pâ¯<â¯0.05). Additionally, fucoidan potentiated mesna protective effect when compared with IFOâ¯+â¯mesna group (Pâ¯<â¯0.05). Accordingly, neutrophil depletion with anti-Ly6G reduced inflammatory parameters and bladder injury compared to IFO (Pâ¯<â¯0.05). In contrast, G-CSF enhanced IFO (200â¯mg/kg)-induced HC, which was significantly attenuated by treatment with fucoidan (Pâ¯<â¯0.05). Therefore, neutrophils contribute to the pathogenesis of HC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 62, September 2018, Pages 96-108
Journal: International Immunopharmacology - Volume 62, September 2018, Pages 96-108
نویسندگان
AmÃlcar Figueiredo Dornelas-Filho, Venúcia Bruna Magalhães Pereira, Deysi Viviana Tenazoa Wong, LÃvia Maria Soares Nobre, Anielle Torres Melo, Camila Meirelles Souza Silva, Carlos Wagner Souza Wanderley, Mariana Lima Nour,