Higher Activity of Alcohol Dehydrogenase Is Correlated with Hepatic Fibrogenesis
| Autor: | Jie Gao, Na Gao, Bing Qi, Ming-Rui Li, Gao-Ju Wang, Jing Li, Zhao Wang, Hai-Ling Qiao |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Liver Cirrhosis Male 0301 basic medicine medicine.medical_specialty Carcinoma Hepatocellular Cirrhosis Aldehyde dehydrogenase Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Fibrosis Internal medicine medicine Carcinoma Animals Humans Risk factor Aged Alcohol dehydrogenase Pharmacology biology business.industry Liver Neoplasms Alcohol Dehydrogenase Aldehyde Dehydrogenase Middle Aged medicine.disease Aldehyde Oxidoreductases Rats Proliferating cell nuclear antigen Isoenzymes 030104 developmental biology Endocrinology Liver 030220 oncology & carcinogenesis Hepatocellular carcinoma biology.protein Molecular Medicine Female business |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 367:473-482 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Hepatofibrosis can progress to cirrhosis and hepatocellular carcinoma (HCC). Prevention, stabilization, and reversal of disease progression are vital for patients with hepatofibrosis, and identifying the risk factors for hepatofibrosis is urgently needed. In this study, we examined the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the fibrotic livers of HCC patients (n = 88) and comparied these results with activities in patients with normal livers (n = 74). A fibrosis-carcinoma rat model was used to study the activity of ADH in fibrosis and HCC and the relationship between innate ADH activity and the extent of hepatofibrosis or HCC. Substantial interindividual variations were found in the activities of ADH and ALDH in normal livers. The activity levels of total ADH, ADHI, and ADHII in fibrotic livers were significantly higher than those in normal livers (P < 0.001), whereas the activity of ALDH was slightly greater. The positive rates of ADHI and ADHII were 84.1% and 77.3%, respectively; the areas under the receiver operator characteristics (ROC) curve were 0.943 and 0.912, respectively. For the rat model compared with controls, ADH activity in liver was significantly increased at the fibrotic and HCC stages, and no significant difference was noted between ADH activity in the liver at these two stages. The innate activity of ADH in serum was well correlated with the extent of hepatofibrosis as indicated by Masson area%, Ki67+%, proliferating cell nuclear antigen +%, and GST-p average density at fibrotic stage but not at HCC stage. A higher level of activity of ADH is a risk factor for hepatofibrogenesis and might be a prevention target for hepatofibrosis. |
| Databáze: | OpenAIRE |
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