Quercetin ameliorates polychlorinated biphenyls-induced testicular DNA damage in rats.

Polychlorinated biphenyls (PCBs) are a group of environmental contaminants widely reported to cause gonadal toxicity in both humans and animals. This study investigated the amelioratory role of quercetin in PCBs-induced DNA damage in male Wistar rats. Polychlorinated biphenyls were administered intraperitoneally at a dose of 2 mg kg(-1) alone or in combination with quercetin (orally) at 50 mg kg(-1) for 25 days. Quercetin modulation of PCBs-induced gonadal toxicity was evaluated using selected oxidative stress indices, comet assay, measurement of DNA concentration and histology of the testes. Administration of PCBs alone caused a significant (P < 0.05) depletion in the total thiol level in testes of treated rats. Conversely, the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) production were markedly elevated in testes of PCBs-treated rats compared with control. Further, PCBs exposure produced statistically significant increases in DNA tail migration, degraded double-stranded DNA (dsDNA) concentration and histological alterations of testes of the treated rats compared to control. Quercetin cotreatment significantly improved the testicular antioxidant status, decreased DNA fragmentation and restored the testicular histology, thus demonstrating the protective effect of quercetin in PCBs-treated rats.

Redox signalling and the inflammatory response in rheumatoid arthritis.

Reactive oxygen species (ROS) are produced mainly during oxidative phosphorylation and by activated phagocytic cells during oxidative burst. The excessive production of ROS can damage lipids, protein, membrane and nucleic acids. They also serve as important intracellular signalling that enhances the inflammatory response. Many studies have demonstrated a role of ROS in the pathogenesis of inflammatory chronic arthropathies, such as rheumatoid arthritis. It is known that ROS can function as a second messenger to activate nuclear factor kappa-B, which orchestrates the expression of a spectrum of genes involved in the inflammatory response. Therefore, an understanding of the complex interactions between these pathways might be useful for the development of novel therapeutic strategies for rheumatoid arthritis.

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.

[Experimental cirrhosis induced by carbon tetrachloride inhalation: adaptation of the technique and evaluation of lipid peroxidation]. / Cirrose experimental induzida pela inalação de tetracloreto de carbono: adaptação da técnica e avaliação da peroxidação lipídica.

BACKGROUND: Long-term administration of carbon tetrachloride is an accepted experimental model to produce hepatic fibrosis. Oxidative stress has been postulated as a major molecular mechanism involved in carbon tetrachloride hepatotoxicity, where the reactive oxygen species play an important role in the pathogenesis of liver fibrosis. AIMS: This study was conducted to evaluate the effectiveness of an experimental model of hepatic cirrhosis induced by carbon tetrachloride inhalation as well as the importance of lipid peroxidation and the characteristics of the ascitic fluid in this model. METHODS: At first the hepatic histologic findings were assessed using the hematoxilineosin technique in different moments of carbon tetrachloride inhalation (5th, 7th, 9th, 12th weeks). Later, at the end of 15 weeks of the study the rats were divided in three groups (control; control + phenobarbital; and carbon tetrachloride + phenobarbital) for lipid peroxidation, ascitic fluid and histologic characteristics evaluation. For the lipid peroxidation analysis, thiobarbituric acid and QL techniques were used. Cytologic and bacteriologic parameters were analysed in the ascitic fluid. RESULTS: Cirrhosis was established in 100% of carbon tetrachloride rats between the 12th and 15th weeks with an elevation in the lipid peroxidation carbon tetrachloride rats' livers. Ascitic fluid infection was observed in one of seven rats who has developed ascites. CONCLUSIONS: The carbon tetrachloride inhalation method developed in this study is effective in cirrhosis induction and ascites formation, and the carbon tetrachloride cirrhosis physiopathogenesis is probably related to the oxidative stress installation.

[Chronic anemia protects against gastric damage by alcohol and aspirin. The role of the toxic radicals and lipid peroxidation]. / La anemia crónica protege el daño gástrico por alcohol y aspirina. Papel de los radicales tóxicos y de la peroxidación lipídica.

The effects of chronic anemia on gastric damage induced by ethanol or aspirin have been investigated in rats. The role of free radicals and lipid peroxidation in that circumstance was also assessed. Chronic anemia was induced by replacement of 1.5 ml of blood by a plasma expander during 5 days. Under anesthesia, the stomach was perfused with 100% ethanol or acidified aspirin during 30 minutes. Thereafter, the rats were sacrificed, the stomachs removed and analyzed planimetrically for macroscopic damage. In addition, gastric tissue was collected and homogenized for assessment of toxic free radicals generation by chemoluminicense and lipid peroxidation by measuring reactive species of thiobarbituric acid (TBA-RS). Chronic anemia significantly protected against damage induced by ethanol or aspirin. The rate of toxic free radicals and the TBA-RS in the gastric mucosa was significantly reduced by anemia, either under ethanol or aspirin injury. It is concluded that anemia offers a general protection against gastric mucosal damage and that this protection is in part mediated by limitations on lipid peroxidation and toxic free radicals generation.