کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
8552738 1562272 2018 57 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Transporter-dependent cytotoxicity of antiviral drugs in primary cultures of human proximal tubular cells
ترجمه فارسی عنوان
سیتوتوکسیسیت وابسته به حملونقل از داروهای ضد ویروسی در کشت های اولیه سلول های لوله ای پروگزیمال
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
The role of plasma membrane transporters in the nephrotoxicity of two antiretroviral drugs, cidofovir and tenofovir, was studied in primary cultures of human proximal tubular (hPT) cells. Cells were grown on Transwell filter inserts to maintain epithelial polarity and access to either the apical or basolateral plasma membrane. The function of relevant membrane transporters, organic anion transporter 1 and 3 (OAT1/3), P-glycoprotein (multidrug resistance protein-1; P-gp or MDR1), and organic cation transporter 2 (OCT2), was validated by measurements of apical-to-basolateral and basolateral-to-apical fluxes of furosemide, digoxin, and metformin, respectively. Acute cytotoxicity of cidofovir (0, 10, 50, 150, or 300 μM) in the absence or presence of 500 μM probenecid, tenofovir disoproxil fumarate (0, 20, 90, 180, or 360 μM) in the absence or presence of 500 μM probenecid, or cisplatin (0, 20, 90, 180, or 360 μM) as a positive control in the absence or presence of 500 μM cimetidine, was assessed after 4-h incubations by determinations of release of lactate dehydrogenase (LDH), γ-glutamyltransferase (GGT), N-acetyl-β-d-glucosaminidase (NAG), or Kidney Injury Molecule-1 (KIM-1). Cell death generally agreed with each of the four biomarkers, was generally greater when cidofovir or tenofovir was added to the upper compartment, and was markedly diminished in the presence of the appropriate transport inhibitor. Additionally, the extent of cytotoxicity caused by the two antiviral drugs was similar to that caused by cisplatin. The results demonstrate the importance of plasma membrane transport of antiviral drugs to elicit cytotoxicity in the hPT cell.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volumes 404–405, 1 July 2018, Pages 10-24
نویسندگان
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