کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2498817 1116469 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effect of alcohol on diethylnitrosamine-induced hepatic toxicity: Critical role of ROS, lipid accumulation, and mitochondrial dysfunction
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم دامی و جانورشناسی
پیش نمایش صفحه اول مقاله
Effect of alcohol on diethylnitrosamine-induced hepatic toxicity: Critical role of ROS, lipid accumulation, and mitochondrial dysfunction
چکیده انگلیسی

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh in women worldwide. Chronic heavy alcohol consumption is a major risk factor for the development of HCC. However, the mechanism underlying the direct association between alcohol consumption and HCC is far from completely understood. In the present study, we investigated the effect of chronic consumption of alcohol on diethylnitrosamine (DEN)-induced cytotoxicity, which was essential for the malignant transformation. We showed that alcohol deceased survival of mice treated by DEN and promoted DEN-induced toxicity and hepatic injury. In addition, alcohol promoted DEN-induced increase of proinflammatory factors, collagen content and fibrosis-related genes, including collagen1, 3 and 4, TMIP1, TIMP2 and TGFβ1, and compensatory proliferation. Alcohol may increase alcohol dehydrogenase (ADH) and cytochrome P4502E1 (CYP2E1) expression, enhanced reactive oxygen species (ROS) generation, and resulted in a vicious circle between ROS generation, lipid accumulation, and mitochondrial dysfunction, aggravating liver injury and toxicity in DEN-treated mice. These results demonstrated that the combination of alcohol and carcinogens could aggravate carcinogen-induced cytotoxicity in the early phase of rumourigenesis through ADH and CYP2E1-generated ROS and the resultant cytotoxic process. The present study provided direct experimental evidence for alcohol-promoted toxicity and hepatic injury in carcinogen (DEN)-treated mice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental and Toxicologic Pathology - Volume 67, Issue 10, October 2015, Pages 491–498
نویسندگان
, , , , , , , ,