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Aldosterone antagonist inhibits fibrosis-induced NOX4 protein expression in hepatic cells and tissues of rats / 中华肝脏病杂志
Chinese Journal of Hepatology ; (12): 519-523, 2013.
Article in Chinese | WPRIM | ID: wpr-278044
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory potential of aldosterone antagonist on NOX4 protein expression in hepatic fibrosis by using a rat model of carbon tetrachloride (CCl4)-induced hepatotoxicity.</p><p><b>METHODS</b>Twenty-four male Wistar rats were randomly divided into three equal groups fibrosis model group (receiving three subcutaneous injections per week of 2.5 ml/kg 40% CCl4); spironolactone (Sp)-treated fibrosis model group (receiving CCl4 regimen plus three injections per day of 20 mg/kg Sp in olive oil); negative-treatment fibrosis model group (receiving CCl4 regimen plus three injections per day of olive oil alone). Unmanipulated rats (receiving no CCl4 and no supplemental treatments) served as normal controls. After 4 weeks, liver histology was carried out to assess cytotoxicity (by hematoxylin-eosin staining), fibrosis (by Masson staining and METAVIR scoring), and NOX4 protein expression (by immunohistochemistry). In addition, in vitro analyses of immortalized rat hepatic stellate cells, HSC-T6, were performed to evaluate dose-response (10-9, 10-7 and 10-5 mol/L) and time-response (6, 12 and 24 h) of aldosterone agonist (Ald) and an aldosterone antagonist, eplerenone (EPLE). Effects on NOX4 protein expression were evaluated by western blotting.</p><p><b>RESULTS</b>The fibrosis model group showed significantly more fibrosis than the normal control group (16.060 +/- 0.300 vs. 2.471 +/- 0.160, P = 0.000]; however, the Sp-treated fibrosis model group showed significantly less CCl4-induced fibrosis (5.761 +/- 0.152 vs. model 16.060 +/- 0.300, P = 0.000). The fibrosis model group also showed significantly higher NOX4 protein expression in liver tissues than the normal control group (7.231 +/- 0.211 vs. 1.350 +/- 0.252, P = 0.000), and the Sp-treated fibrosis model tissues showed significantly less CCl4-induced up-regulated NOX4 protein expression (4.270 +/- 0.242 vs. model 7.231 +/- 0.211, P = 0.000]. Ald induced up-regulated NOX4 protein expression in HSC-T6 cells in dose- and concentration-dependent manners, with the peak expression being induced by the 10-5 mol/L concentration and 24 h exposure. The Ald-treated cells expressed significantly more NOX4 protein than the untreated control cells (0.710 +/- 0.011 vs. 0.316 +/- 0.015, P = 0.000]. and the EPLE-treated cells showed significantly less Ald-induced up-regulated NOX4 expression (0.615 +/- 0.014 vs. 0.710 +/- 0.011, P = 0.000].</p><p><b>CONCLUSION</b>Aldosterone antagonists inhibit the fibrosis-induced NOX4 protein expression in rat hepatic cells.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Cell Line / Rats, Wistar / NADPH Oxidases / Mineralocorticoid Receptor Antagonists / NADPH Oxidase 4 / Liver Cirrhosis, Experimental / Metabolism Type of study: Prognostic study Limits: Animals Language: Chinese Journal: Chinese Journal of Hepatology Year: 2013 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Cell Line / Rats, Wistar / NADPH Oxidases / Mineralocorticoid Receptor Antagonists / NADPH Oxidase 4 / Liver Cirrhosis, Experimental / Metabolism Type of study: Prognostic study Limits: Animals Language: Chinese Journal: Chinese Journal of Hepatology Year: 2013 Type: Article