کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485457 | 1114355 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effect of Rat Serum Lipoproteins on mRNA Levels and Amiodarone Metabolism by Cultured Primary Rat Hepatocytes
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Hyperlipidemia can significantly increase amiodarone (AM) in vivo liver uptake and decrease its velocity of microsomal metabolism. Here, hepatocytes isolated from normolipidemic (NL) and hyperlipidemic rats were incubated with AM in the presence or absence of diluted NL or hyperlipidemic serum. The serum was added either as preincubation before drug, or concurrently with drug; incubations without rat serum were used as controls. The hepatocyte levels of mRNA for several proteins and enzymes were also measured. Disappearance of AM was seen up to 72Â h. There was little difference between hepatocytes from NL or hyperlipidemic animals in intrinsic clearance (CLint) of AM. The effect of hyperlipidemic rat serum, either before or with AM, was profound, causing a significant reduction in the CLint. Reductions were seen in mRNA for cytochrome P450 1A1, 3A2, and 2D1, some transporters, and lowâdensity lipoprotein receptors after exposure of hepatocytes to lipoproteinârich sera. In conclusion, exposure of isolated hepatocytes to hyperlipidemic serum caused decreases in AM CLint and lower mRNA levels for some proteins involved in the uptake and metabolism of AM. When coincubated with serum, an additional effect of increased binding to lipoproteins seemed to further contribute to a reduced CL of AM.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 1, January 2013, Pages 262-270
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 1, January 2013, Pages 262-270
نویسندگان
Dion R. Brocks, Dalia A. Hamdy, Mohamed BenâEltriki, Jigar P. Patel, Ayman O. ElâKadi,