文章基本信息

标题：Erlotinib can halt adenine induced nephrotoxicity in mice through modulating ERK1/2, STAT3, p53 and apoptotic pathways
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作者：Ahmed M. Awad ; Mohamed A. Saleh ; Nashwa M. Abu-Elsaad 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-13
DOI：10.1038/s41598-020-68480-7
出版社：Springer Nature
摘要：Renal fibrosis is a failed regenerative process that facilitates chronic kidney disease progression. The current study was designed to study the effect of erlotinib, a receptor tyrosine kinase inhibitor, on the progression of renal fibrosis. The study included four groups of mice: control group; adenine group: received adenine (0.2% w/w) daily with food for 4 weeks; erlotinib group: received 80 mg/kg/day erlotinib orally (6 ml/kg/day, 1.3% w/v suspension in normal saline 0.9%) for 4 weeks; adenine erlotinib group: received adenine and erlotinib concurrently. Kidney function and antioxidant biomarkers were measured. Renal expression of Bcl2 and p53 and histopathological changes (tubular injury and renal fibrosis) were scored. Renal tissue levels of transforming growth factor-β1, p-ERK1/2 and p-STAT3 were measured. Results obtained showed significant decrease (P < 0.001) in serum creatinine, urea and uric acid in erlotinib adenine group. Level of malondialdehyde was decreased significantly (P < 0.001) while reduced glutathione and catalase levels were increased (P < 0.01) by erlotinib concurrent administration. Erlotinib markedly reduced fibrosis and tubular injury and decreased TGF-β1, p-ERK1/2 and p-STAT3 (P < 0.5). In addition, expression level of Bcl-2 was elevated (P < 0.001) while that of p53-was reduced compared to adenine alone. Erlotinib can attenuate renal fibrosis development and progression through anti-fibrotic, antioxidant and anti-apoptotic pathways.