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العنوان
Effect of NLRP3 inflammasome inhibition on experimentally induced kidney dysfunction /
المؤلف
El-Sayed, Mohammed Sameh Ibrahim.
هيئة الاعداد
باحث / محمد سامح إبراهيم السيد إبراهيم
مشرف / منار أحمد نادر
مشرف / نشوى محمد أبوالسعد
مناقش / ميمي حجازي محمود
مناقش / أحمد رمضان الشيخ
الموضوع
Acute renal failure - Prevention. Kidney - Drug effects. Kidney Diseases - Chemically induced. Kidney Function Tests - Methods. Toxicity Tests - Methods.
تاريخ النشر
2021.
عدد الصفحات
online resource (172 pages) :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
علم السموم
تاريخ الإجازة
1/1/2021
مكان الإجازة
جامعة المنصورة - كلية الصيدلة - قسم الأدوية والسموم.
الفهرس
Only 14 pages are availabe for public view

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from 172

Abstract

Aims : Chemical renal toxicity is common and has limited therapeutic interventions. The NLRP3 inhibitor dapansutrile (DAPA) undergoes clinical phase II trials and it shows promising beneficial effects in various inflammatory diseases. The current study aims at evaluating the effect of DAPA on folic acid (FA) induced acute kidney injury (AKI) and its possible transition to chronic injury. Materials and methods: Two treatment protocols were studied depending on DAPA injection timing. A prophylactic protocol involving the injection of DAPA (0.2 mg/kg) daily for seven days before FA challenge and a therapeutic protocol where DAPA was injected after FA. Each protocol included four groups of rats: control group, DAPA group, FA group and DAPA+FA group. Serum creatinine, urea and uric acid were measured. Also, kidney injury, necrosis and fibrosis percentage in addition to infiltration of CD68 positive cells were evaluated. Activation markers of inflammasome and the expression of Ki-67 and LC-3 were measured. Key findings: Results showed an improvement in renal tissue integrity and a significant decrease in kidney function biomarkers, caspase-1, IL-1β and IL-18 by DAPA injection (p < 0.05). In addition, DAPA decreased the proliferation marker Ki-67 and the autophagic marker LC-3 (p < 0.01). Significance: DAPA potentially alleviates FA induced nephrotoxicity through targeting inflammasome/caspase-1/ IL axis. Moreover, it shows a regulatory effect on renal regeneration and autophagy. Screen reader support enabled.