Evaluation of the protective effects of quercetin in the hepatopulmonary syndrome.
The hepatopulmonary syndrome (HPS) occurs when intrapulmonary dilatation causes hypoxemia in cirrhosis. The free radicals may play a significant contributory role in the progression of HPS, and flavonoid agents could protect against deleterious effects of free radicals. The flavonoid quercetin was evaluated in an experimental model of biliary cirrhosis induced by bile duct ligation (BDL) in rats. Quercetin was administered at 50mg/kg for 14 days to cirrhotic and non-cirrhotic rats. Bone marrow was extracted from animals to analyze micronuclei. Lung, liver and blood were extracted to detect DNA damage using the comet assay. The results showed that the micronuclei and DNA damages to lung and liver were increased in BDL rats. Quercetin caused no damage to the DNA while decreasing the occurrence of micronucleated cells in bone marrow as well as DNA damage to lung and liver in cirrhotic rats. Quercetin showed antimutagenic activity against hydroperoxides as evaluated by the oxidative stress sensitive bacterial strains TA102 Salmonella typhimurium and IC203 Escherichia coli, suggesting protection by free radical scavenging. In Saccharomyces cerevisie yeast strains lacking mitochondrial or cytosolic superoxide dismutase, these results indicate that quercetin protects cells by induction of antioxidant enzymes. The present study is the first report of genotoxic/antigenotoxic effects of quercetin in a model of animal cirrhosis. In this model, quercetin was not able to induce genotoxicity and, conversely, it increased the genomic stability in the cirrhotic rats, suggesting beneficial effects, probably by its antioxidant properties.
Tieppo
J
J
Hospital de Clínicas de Porto Alegre, HCPA/Universidade Federal do Rio Grande do Sul, UFRGS, 90035-903, Laboratório de Hepatologia Experimental, Fisiologia, Ramiro Barcelos, 2350 Porto Alegre, RS, Brazil.
Vercelino
R
R
Dias
A S
AS
Silva Vaz
M F
MF
Silveira
T R
TR
Marroni
C A
CA
Marroni
N P
NP
Henriques
J A P
JA
Picada
J N
JN
D000818:Animals; D016587:Antimutagenic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001652:Bile Ducts / Q000601:surgery; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D020552:Comet Assay; D004249:DNA Damage; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D020065:Hepatopulmonary Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism
D016587:Antimutagenic Agents; D000975:Antioxidants; D011794:Quercetin