title: Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats.
abstract: Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1ml/kg 10% CCL4in olive oil three times/week (every other day) for 12weeks to induce hepatic cirrhosis. Carvedilol (10mg/kg/day suspended in 0.5% CMC orally), silymarin (50mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL4induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries.
authors.affiliation: Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta, Egypt. Electronic address: Mohamed.Balaha@Med.Tanta.Edu.Eg.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Balaha
authors.affiliation: Histology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta, Egypt.
authors.forename: Samah
authors.initials: S
authors.lastname: Kandeel
authors.affiliation: Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta, Egypt.
authors.forename: Waleed
authors.initials: W
authors.lastname: Barakat
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D063646:Carcinogenesis; D000077261:Carvedilol; D002908:Chronic Disease; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests; D008114:Liver Neoplasms, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D015850:Interleukin-6; D011412:Propanolamines; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D000077261:Carvedilol
keywords: CCL(4); Carvedilol; E & N-cadherin; Hepatic cirrhosis; Hepatocellular cancer; IL-6