Effects of Quercetin on Liver Damage in Rats with Carbon Tetrachloride-Induced Cirrhosis

ULBRA-Cachoeira do Sul e Canoas, Brasil.
Digestive Diseases and Sciences (Impact Factor: 2.61). 05/2003; 48(4):824-9. DOI: 10.1023/A:1022869716643
Source: PubMed


Flavonoids are reported to exhibit a wide variety of biological effects, including antioxidant and free radical-scavenging activities. Evidence of oxidative reactions is often associated with various chronic disease processes characterized by accumulation of connective tissue. This study was aimed to investigate the protective effects of chronic administration of the flavonoid quercetin (150 micromol/kg body wt/day intraperitoneally) in rats with carbon tetrachloride-induced fibrosis. In animals rendered cirrhotic by administration of carbon tetrachloride for 16 weeks, cell necrosis, fibrosis, and inflammatory infiltration were found. Histological abnormalities were accompanied by a higher hepatic content of collagen and thiobarbituric acid-reactive substances. Expression of inducible nitric oxide synthase (iNOS) was significantly increased in the liver. Treatment with quercetin during 3 weeks improved liver histology and reduced collagen content, iNOS expression, and lipid peroxidation. Those effects were associated with an increased total peroxyl radical-trapping antioxidant capacity of liver. We conclude that quercetin is effective in this model of liver damage.

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    • "The most abundant flavonols in onions are derivatives of quercetin, mainly quercetin 4′-O-glucoside and quercetin 3,4′-O-diglucoside (González-Peña et al., 2013). Quercetin has been associated to reduction of lipids in hepatic tissue and hyperlipidaemia in obese mice induced by an atherogenic diet (Park, Ahn, Kim, & Ha, 2008) through oxidation of fatty acids (Czeczot, 2000) and also showing hepatoprotective effects (Cipak, Novotny, Cipakova, & Rauko, 2003; Le Marchand, Murphy, Hankin, Wilkens, & Kolonel, 2000; Pavanato et al., 2003; Peres et al., 2000). Despite these positive effects on lipid metabolism, very little information is available on the role of Allium spices in fatty acid composition and lipid metabolism. "
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    ABSTRACT: The complex biochemical composition of onions has been studied as a source of biological components with health-related properties. The evolution of hypercholesterolemia is associated with a large range of alterations considered as strong risk factors for many cardiovascular events. The objective of this study was to investigate the effects of onion as functional ingredient on plasma, erythrocyte, liver and adipose tissue fatty acid composition in hypercholesterolemic male Wistar rats. Rats (n=24) were randomly divided into three groups: control (C), high-cholesterol (HC), and high-cholesterol enriched with onion (HCO) groups. At the end of 7weeks, animals were anesthetized and euthanized by extracting blood by cardiac puncture. Plasma, erythrocytes, liver and adipose tissue were collected and immediately stored at −80°C. Fatty acid methyl esters were identified and quantified by GC/MS. Total fatty acid concentration decreased in liver and adipose tissue both in HC and HCO groups. SFA content was significantly higher in plasma, erythrocytes and liver in the C group compared to HC and HCO groups. In contrast, SFAs increased in adipose tissue both in HC and HCO groups compared to the C group. A significant increase in MUFA content in plasma was found in HC and HCO groups compared to the C group; in erythrocytes and liver the increase was lower. In plasma, PUFA content was significantly lower in HC and HCO groups compared to the C group. Interestingly, in liver and adipose tissue, PUFAs increased in HC and HCO groups compared to the C group. Results showed noticeable effects on individual fatty acid composition when assaying high-cholesterol diets in rats, in some cases enhanced by onion enrichment. Further research is needed to deeper understand the involved mechanisms and pathways.
    Full-text · Article · Oct 2014
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    • "Moreover, our previous study reported that quercetin could inhibit pulmonary fibrosis (10). The effects of quercetin on liver damage induced by carbon tetrachloride, hepatotoxins, or bile duct obstruction have been previously studied (11-14). However, the effect of quercetin on liver damage based on immunological mechanisms is not yet known. "
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    ABSTRACT: Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.
    Preview · Article · Aug 2014 · Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.]
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    • "The protective effects of quercetin against chemically induced tissue pathologies are widely known. For example, quercetin protects carbon tetrachloride-induced hepatotoxicity, 2,4-D-induced oxidative damage in spermatogonial cells, ethanol-induced oxidative stress, cyclosporin-induced nephrotoxicity, cisplatin-induced cytotoxicity in cultured tubular epithelial cells, atrazine (ATZ)-induced cytotoxicity in cultured Sertoli-germ cells and Leydig cells.[2345678] Many of these beneficial effects of quercetin are considered to be related to the experimental situation, antioxidant properties of quercetin, and the dose of quercetin used.[9] "
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    ABSTRACT: Background:The conflicting roles of quercetin against tissue pathologies associated with oxidative stress are known.Objective:To evaluate the effect of quercetin at doses of 5 mg/kg (Q5) or 10 mg/kg (Q10) against atrazine (120 mg/kg, ATZ)-induced oxidative stress in various tissues of rats.Materials and Methods:Adult male albino Wistar rats were administered ATZ, Q5, and Q10 alone or in combination for 16 days. At the end of the 16th day, the animals were sacrificed by cervical dislocation; and the blood, heart, brain, kidney and liver were collected and used for biochemical determinations and histopathological examination.Results:Q10 but not Q5 attenuated ATZ-induced increase in the levels of serum enzyme markers sorbitol dehydrogenase (SDH), acid phosphatase (ACP), alkaline phosphatase (ALP), and aspartate aminotransferase (AST). The heart was less susceptible to ATZ-induced oxidative stress than the liver, kidney, and brain of treated animals, and there were tendencies for synergistic effects in the heart and liver of Q5 + ATZ-treated rats. Oxidative stress-induced by ATZ in terms of increased lipid peroxidation level and superoxide dismutase (SOD) activity was decreased in the brain of the Q5 + ATZ-treated rats but not that of the Q10 + ATZ-treated rats. Conversely, histopathological changes and oxidative stress-induced by ATZ in terms of elevated lipid peroxidation level, decreased SOD, and catalase (CAT) activities were prevented in the kidney and liver of the Q10 + ATZ-treated rats but not that of the Q5 + ATZ-treated rats.Conclusion:Quercetin at the investigated doses and especially the low dose may not protect against ATZ-induced oxidative stress in rat tissues in an overall sense.
    Full-text · Article · May 2014 · Toxicology International
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