کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2598916 1133167 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lithocholic acid feeding results in direct hepato-toxicity independent of neutrophil function in mice
ترجمه فارسی عنوان
تغذیه اسید لیتوکوکول باعث کاهش مستقیم هپاتوسیت سیتیکی از عملکرد نوتروفیل در موش می شود
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


• Lithocholic acid (LCA) feeding results in significant hepatotoxicity and neutrophil recruitment.
• Ablation of neutrophil function and activity does not protect against LCA induced injury.
• Tauro-LCA and tauro-chenodeoxycholic acid accumulate to toxic levels after LCA feeding.
• Direct bile acid toxicity can occur when toxic bile acid species are administered.
• Species differences in bile acid composition may determine mechanistic differences in injury.

Lithocholic acid (LCA) supplementation in the diet results in intrahepatic cholestasis and bile infarcts. Previously we showed that an innate immune response is critical for cholestatic liver injury in the bile duct ligated mice. Thus, the purpose of this study was to investigate the role of neutrophils in the mechanism of liver injury caused by feeding mice a diet containing LCA. C57BL/6 mice were given control or 1% LCA containing diet for 24–96 h and then examined for parameters of hepatotoxicity. Plasma ALT levels were significantly increased by 48 h after LCA feeding, which correlated with both neutrophil recruitment to the liver and upregulation of numerous pro-inflammatory genes. The injury was confirmed by histology. Deficiency in intercellular adhesion molecule-1 (ICAM-1) expression or inhibition of neutrophil function failed to protect against the injury. Bile acid levels were quantified in plasma and bile of LCA-fed mice after 48 and 96 h. Only the observed biliary levels of taurochenodeoxycholic acid and potentially tauro-LCA caused direct cytotoxicity in mouse hepatocytes. These data support the conclusion that neutrophil recruitment occurs after the onset of bile acid-induced necrosis in LCA-fed animals, and is not a primary mechanism of cell death when cholestasis occurs through accumulation of hydrophobic bile acids.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 228, Issue 1, 3 July 2014, Pages 56–66
نویسندگان
, , , , , , ,