Retraction Note: Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model.

The article "Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model", by N.D. Suarez Uribe, M.F. Pezzini, J. Dall'Agnol, N. Marroni, S. Benitez, D. Benedetti, J. Da Silva, C.T. Cerski, E. Dallegrave, S. Macedo, S.C.W.S.E.F. de Oliveira, D. Joveleviths, published in Eur Rev Med Pharmacol Sci 2023; 27 (13): 6374-6383-DOI: 10.26355/eurrev_202307_32997-PMID: 37458654 has been retracted by the Editor in Chief for the following reasons: After publication, concerns were raised by an unidentified reader who underlined some similarities between this publication and a previous publication published in the Journal of Clinical and Experimental Gastroenterology. After being informed, the authors claimed the previous journal published the article without consent, and, therefore, the authors promptly withdrew the previous publication. The retraction published by the other journal does not contain any information regarding the reason for withdrawal. As a matter of fact, the journal does not have any evidence about the authors' claim and still considers this research a duplicate publication. For the above-mentioned reasons, the Editor in Chief decided to withdraw the manuscript. This manuscript has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32997.

Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model.

OBJECTIVE: Mancozeb is one of the most widely used Ethylenebisdithiocarbamates fungicides in Brazil. A pilot experimental model was created to evaluate its potential hepatotoxic effect. MATERIALS AND METHODS: An experimental study was performed with 27 male Wistar rats (3 groups). The Control Group received a saline solution, while Intervention Groups I and II received 250 mg/kg and 500 mg/kg of Mancozeb respectively, once a week, for 12 weeks. Anthropometric measurements were carried out, and the marker of biological exposure in urine was dosed. Biochemical tests, evaluation micronucleus count, comet and oxidative stress markers assay, and histological assessment of the liver were also performed. RESULTS: The hepatotoxic effect of Mancozeb was confirmed by anthropometric measurements, genotoxicity, and oxidative stress. Statistically significant results were found when the exposed groups were compared to the control group. CONCLUSIONS: These results were supported by inflammatory infiltration and balloonization in the treated groups. The experimental model effectively demonstrated the deleterious effect of Mancozeb on the liver.

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.

Evaluation of the genotoxic effect of rutin and quercetin by comet assay and micronucleus test.

Flavonoids are phenolic compounds, naturally found in vegetables, tea and red wines. A recent study has demonstrated that the flavonoids rutin and quercetin show a protective role against the deleterious effects of free radicals in cirrhotic rats. Considering this finding and the controversial results concerning the mutagenicity of rutin and quercetin recorded in the literature, the capacity of these flavonoids to cause damage to the DNA was evaluated using the alkaline single-cell gel electrophoresis (SCG) and micronucleus test in the bone marrow of mice. The doses for both compounds were 2 x 2500, 2 x 1250 and 2 x 625 mg/kg. Micronucleus test showed that rutin caused no damage to the DNA of the mice bone marrow cells, and the SCG assay demonstrated an increase of damage only at the dose of 2 x 1250 mg/kg. But when the mice cells of the three quercetin doses were compared with the negative control, significantly higher damage was observed by SCG assay, although not proportional to the dose. The micronucleus test also demonstrated a significant increase of damage, but only at the 2 x 1250 mg/kg dose. Considering the results obtained in this study with very high doses, it is unlikely that the consumption of rutin and quercetin produces any clastogenic effects. Our results also indicated that SCG could profitably be used in drug genotoxicity evaluation protocols.

[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.

The flavonoid quercetin ameliorates liver damage in rats with biliary obstruction.

BACKGROUND/AIMS: Our aim was to investigate whether the antioxidant quercetin might protect against liver injury in chronically biliary obstructed rats. METHODS: Secondary biliary cirrhosis was induced by 28 days of bile duct obstruction. Animals received quercetin at 75, 150 and 300 micromol x kg body wt(-1) x day(-1) i.p. through the experimental period or at 150 micromol x kg body wt(-1) x day(-1) i.p. for the last 2 weeks. RESULTS: Bile duct obstruction resulted in a decrease in the activities of antioxidant enzymes. Liver oxidised/reduced (GSSG/GSH) glutathione ratio, hepatic and mitochondrial thiobarbituric acid reactive substances (TBARS) and collagen content were significantly increased and a marked fibrosis and bile ductular proliferation was observed. Quercetin corrected the reduction in glutathione concentration and partially prevented the increase in collagen concentration, TBARS and GSSG/GSH ratio. Treatment resulted in a significant preservation of the activities of antioxidant enzymes, a less pronounced fibrosis and a marked inhibition of bile ductular proliferation. Maximal effects were reached with the intermediate quercetin dose given for 2 or 4 weeks. CONCLUSIONS: Quercetin reduces liver oxidative damage, ductular proliferation and fibrosis in biliary-obstructed rats. These effects suggest that it might be a useful agent to preserve liver function in patients with biliary obstruction.

[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.

Effects of chronic normovolemic anemia on gastric microcirculation and ethanol-induced gastric damage in rats.

The effects of chronic normovolemic anemia on gastric microcirculation and gastric mucosal susceptibility to ethanol-induced gastric damage were investigated in anesthetized rats. Blood exchange by a plasma expander during four consecutive days rendered the animals anemic with a 34% decrease in the baseline hematocrit but without affecting blood volume. Chronic anemia induced a decrease in whole blood viscosity, an increase in gastric mucosal blood flow measured by hydrogen gas clearance, a decrease in gastric vascular resistance, and a decrease in gastric hemoglobin content without changes in the gastric oxygen content, the latter two parameters being measured by reflectance spectrophotometry. Gastric mucosal blood flow was lowered by intragastric administration of 100% ethanol in both anemic and control rats, but the final blood flow was significantly higher in anemic than in control animals. Macroscopic gastric damage induced by ethanol administration was significantly lower in anemic than in control rats. We conclude that chronic normovolemic anemia increases gastric mucosal blood flow and leads a protecting mechanism against gastric mucosal damage induced by absolute ethanol.

Involvement of nitric oxide and prostaglandins in gastric mucosal hyperemia of portal-hypertensive anesthetized rats.

This study investigates the effects of inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME), the inhibition of prostaglandin synthesis with indomethacin and the combined effects on gastric mucosal hyperemia of ketamine-anesthetized rats with portal hypertension induced by partial portal vein ligation. The hydrogen gas-clearance technique was used for measurement of gastric mucosal blood flow. Blood pressure increased with L-NAME administration in a similar manner in portal-hypertensive and sham-operated rats. Low doses of L-NAME (1 and 3 mg/kg, intravenously) caused a significant and dose-dependent reduction in gastric mucosal blood flow in portal-hypertensive rats but had no effect on sham-operated animals. With a higher dose of L-NAME (13 mg/kg, intravenously), a significant decrease in gastric mucosal blood flow was observed in both portal-hypertensive and sham-operated rats. Indomethacin pretreatment (5 mg/kg, subcutaneously) caused a significant decrease in basal gastric mucosal blood flow of portal-hypertensive rats but did not modify this parameter in sham-operated animals. In sham-operated rats pretreated with indomethacin, the lower dose of L-NAME (3 mg/kg) did not significantly modify basal gastric mucosal blood flow. Likewise, pretreatment with indomethacin in sham-operated rats did not augment the significant reduction in gastric mucosal blood flow produced by the higher dose of L-NAME. In portal-hypertensive rats the significant dose-dependent reduction in gastric mucosal blood flow induced by L-NAME (3 and 13 mg/kg) was not significantly altered by pretreatment with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)