Effect of Antioxidant Treatment on Fibrogenesis in Rats with Carbon Tetrachloride-Induced Cirrhosis

Abstract

Aim. This study aimed to assess the antioxidant activity of quercetin (Q) in an experimental model of cirrhosis induced by CCl4 inhalation. Materials and Methods. We used 25 male Wistar rats (250 g) that were divided into 3 groups: control (CO), CCl4, and CCl4 + Q. The rats were subjected to CCl4 inhalation (2x/week) for 16 weeks, and they received phenobarbital in their drinking water at a dose of 0.3 g/dL as a P450 enzyme inducer. Q (50 mg/Kg) was initiated intraperitoneally at 10 weeks of inhalation and lasted until the end of the experiment. Statistical analysis was by ANOVA Student Newman-Keuls (mean ± SEM), and differences were considered statistically significant when P < 0.05. Results. After treatment with quercetin, we observed an improvement in liver complications, decreased fibrosis, as analyzed by picrosirius for the quantification of collagen, and decreased levels of matrix metalloproteinase 2 (MMP-2) compared with the CCl4 group. It also reduced oxidative stress, as confirmed by the decrease of substances reacting to thiobarbituric acid (TBARS), the increased activity of antioxidant enzymes, and the reduced glutathione ratio and glutathione disulfide (GSH/GSSG). Conclusion. We suggest that the use of quercetin might be promising as an antioxidant therapy in liver fibrosis.

Lung and Liver Changes Due to the Induction of Cirrhosis in Two Experimental Models

“…The presence of necrotic foci, fibrotic nodules, the infiltration of lymphocytes, and the fatty changes in liver cells are typical characteristic after the induction of cirrhosis (5,33) . The two experimental models used in this study reinforce and confirm the onset of liver damage and cirrhosis of the liver with consequent changes in gas exchange.…”

Hepatoprotective Effect of Quercetin Pretreatment Against Paracetamol-Induced Liver Damage and Partial Hepatectomy in Rats

“…The superoxide anion and the hydroxyl radical are involved in liver damage resulting from lipid peroxidation and interstitial matrix degradation 8 . Bona et al 9 report that a significant increase in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after inhalation of chloroform in rats was reversed with quercetin administration, supporting the notion that quercetin has antioxidant and hepatoprotective effects. Also, it has been shown that the use of quercetin significantly reduces the biochemical alterations caused by cirrhosis, increasing survival in animals with secondary biliary cirrhosis.…”

“…The duration of treatment and the administration route may interfere with the hepatoprotective effect of quercetin. Miltersteiner 3 , Bona et al 9 and David et al 23 found positive results with intraperitoneal administration of quercetin. Behling et al 6 and Bona et al 9 used periods of 28 days and six weeks respectively.…”

“…Miltersteiner 3 , Bona et al 9 and David et al 23 found positive results with intraperitoneal administration of quercetin. Behling et al 6 and Bona et al 9 used periods of 28 days and six weeks respectively. It is likely that treatment duration impacts the effect of quercetin, and that periods longer than seven days may be be more effective to produce observable results.…”

“…In addition, since the development of fibrosis in liver is progressive and dependent on the activation of hepatic stellate cells, intervals of 24h and 72h are too short to allow observation of significant production of collagen fibers. Other studies with different models of carbon tetrachloride-induced toxic hepatitis 9,18 or a model of methionine-choline deficient diet 19 or studies of arsenite-induced lesions 15 describe attenuation of fibrosis by quercetin. Kawada et al 20 showed that quercetin and other natural phenolics inhibit stellate cell activation by disturbing signal transduction pathways and cell protein expression, thus interrupting the differentiation of stellate cells into myofibroblasts, and the consequent production of collagen type I and II.…”