Quercetin reverses experimental cirrhosis by immunomodulation of the proinflammatory and profibrotic processes

• Published in: Fundamental & clinical pharmacology Vol. 31; no. 6; pp. 610 - 624
• Main Authors: Casas‐Grajales, Sael, Vázquez‐Flores, Luis F., Ramos‐Tovar, Erika, Hernández‐Aquino, Erika, Flores‐Beltrán, Rosa E., Cerda‐García‐Rojas, Carlos M., Camacho, Javier, Shibayama, Mineko, Tsutsumi, Víctor, Muriel, Pablo
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2017
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Blocking; Body weight; Carbon tetrachloride; CCl4; Cell activation; Chronic intoxication; Cirrhosis; Disease Models, Animal; Extracellular matrix; Fibrosis; Flavonoids; hepatic stellate cells; HepG2; Immunomodulation; Inflammation; Interleukin 1; Intoxication; Liver; Liver cirrhosis; Liver Cirrhosis - immunology; Liver Cirrhosis, Experimental - immunology; Liver Cirrhosis, Experimental - pathology; Male; NF-kappa B - drug effects; NF-κB protein; Petrolatum; Pharmacology; Quercetin; Quercetin - pharmacology; Rats; Rats, Wistar; Rodents; TGF‐β; thioacetamide; thioacetamide; hepatic stellate cells; CCl4; HepG2; TGF-β; quercetin; fibrosis; cirrhosis
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12315

The ability of quercetin to reverse an established cirrhosis has not yet been investigated. Therefore, the aim of this study was to examine the efficacy of this flavonoid in reversing experimental cirrhosis. Cirrhosis was induced by intraperitoneal administration of TAA (200 mg/kg of body weight) three times per week for 8 weeks or by intraperitoneal petrolatum‐CCl4 (400 mg/kg of body weight) administration three times per week for 8 weeks. To determine the capacity of quercetin to prevent liver fibrosis, the flavonoid (50 mg/kg of body weight, p.o.) was administered daily to rats during the CCl4 or TAA treatment. To evaluate the ability of quercetin to reverse the previously induced cirrhosis, we first treated rats with CCl4 for 8 weeks, as previously described and then the flavonoid was administered for four more weeks. We found that the liver anti‐inflammatory and antinecrotic effects of quercetin are associated with its antioxidant properties, to the ability of the flavonoid to block NF‐κB activation and in consequence to reduce cytokine IL‐1. The ability of quercetin to reverse fibrosis may be associated with the capacity of the flavonoid to decrease TGF‐β levels, hepatic stellate cell activation, and to promote degradation of the ECM by increasing metalloproteinases. The main conclusion is that quercetin, in addition to its liver protective activity against TAA chronic intoxication, is also capable of reversing a well‐stablished cirrhosis by blocking the prooxidant processes and by downregulating the inflammatory and profibrotic responses.