Methionine concentration in the diet has a tissue-specific effect on chromosomal stability in female mice.

Inadequate nutrient intake can influence the genome. Since methionine is an essential amino acid that may influence DNA integrity due to its role in the one-carbon metabolism pathway, we were interested in whether methionine imbalance can lead to genotoxic events. Adult female Swiss mice were fed a control (0.3% dl-methionine), methionine-supplemented (2.0% DL-methionine) or methionine-deficient (0% DL-methionine) diet over a 10-week period. Chromosomal damage was assessed in peripheral blood using a micronucleus test, and DNA damage was assessed in the liver, heart and peripheral blood tissues using a comet assay. The mRNA expression of the mismatch repair genes Mlh1 and Msh2 was analyzed in the liver. The frequency of micronucleus in peripheral blood was increased by 122% in the methionine-supplemented group (p<0.05). The methionine-supplemented diet did not induce DNA damage in the heart and liver tissues, but it increased DNA damage in the peripheral blood. The methionine-deficient diet reduced basal DNA damage in liver tissue. This reduction was correlated with decreased mRNA expression of Msh2. Our results demonstrate that methionine has a tissue-specific effect because methionine-supplemented diet induced both chromosomal and DNA damage in peripheral blood while the methionine-deficient diet reduced basal DNA damage in the liver.

In vivo genotoxicity and oxidative stress evaluation of an ethanolic extract from piquiá (Caryocar villosum) pulp.

In this study, the ethanolic extract obtained from piquiá pulp was assessed for genotoxicity and oxidative stress by employing the micronucleus test in bone marrow and peripheral blood cells in addition to comet, thiobarbituric-acid-reactive substances (TBARS), and reduced glutathione assays in the liver, kidney, and heart. Additionally, phytochemical analyses were performed to identify and quantify the chemical constituents of the piquiá extract. Wistar rats were treated by gavage with an ethanolic extract from piquiá pulp (75 mg/kg body weight) for 14 days, and 24 h prior to euthanasia, they received an injection of saline or doxorubicin (15 mg/kg body weight, intraperoneally). The results demonstrated that piquiá extract at the tested dose was genotoxic but not mutagenic, and it increased the TBARS levels in the heart. Further studies are required to fully elucidate how the properties of ethanolic extract of piquiá pulp can affect human health.

Genotoxicity assessment of Copaiba oil and its fractions in Swiss mice.

Copaiba oil-resin, extracted from the trunk of Copaifera, and traditionally used in folk medicine in the treatment of various disorders, has been shown to be an effective antiinflamatory, antitumor, antitetanus, antiseptic and anti-blenorrhagea agent. As, there are few studies evaluating its genotoxicity, this aspect of the commercial oil-resin, and its volatile and resinous fractions, were evaluated in mice by comet assay and micronucleus (MN) test. A single dose of oil resin, volatile or resin fractions (500; 1,000 or 2,000 mg/kg b.w.) was administered by gavage. The chemical compositions of Copaiba oil resin and its fractions was analyzed by gas chromatography. According to comet assaying, treatment with either one did not increase DNA damage, and as to MN testing, there was no alteration in the incidence of micronucleated polychromatic erythrocytes. Chromatographic analysis of the oil-resin itself revealed sesquiterpenes, diterpenic carboxylic acid methyl esters and high levels of ß-caryophyllene. Thus, it can be assumed that the oil resin and volatile and resinous fractions from the commercial product are not genotoxic or mutagenic.

Antigenotoxic effects of piquiá (Caryocar villosum) in multiple rat organs.

This study investigated the in vivo genotoxicity of piquiá pulp (Caryocar villosum) and its potential antigenotoxicity on doxorubicin (DXR)-induced DNA damage by comet assay and micronucleus test. In addition, the phytochemicals present in piquiá pulp were determined. Piquiá fruit pulp (75, 150 or 300 mg/kg b.w.) was administered by gavage to Wistar rats for 14 days, and the animals received an injection of saline or DXR (15 mg/kg b.w., i.p.) 24 h before they were euthanized. The phytochemical analysis revealed the presence of carotenoids; phenolic compounds, including flavonoids; tannins and α-tocopherol in piquiá pulp. No statistically significant differences were observed in the evaluated parameters, demonstrating the absence of cytotoxic and genotoxic effects of piquiá pulp at all tested doses. In liver, kidney, cardiac and bone marrow cells, piquiá significantly reduced the DNA damage induced by DXR. Our results showed that the lowest piquiá dose caused the largest decrease in DNA damage and the highest dose caused the smallest decrease, demonstrating an inverse dose-response of piquiá pulp. Furthermore, we observed a difference in the potential antigenotoxic effects in several tissues. In conclusion, our results demonstrated that piquiá pulp was not genotoxic and inhibited the genotoxicity induced by DXR, but some of the protective effects that were observed depended on the doses and experimental conditions. Therefore, further investigations are needed to clarify how piquiá pulp positively affects human health.

Evaluation of the genotoxic and antigenotoxic effects after acute and subacute treatments with açai pulp (Euterpe oleracea Mart.) on mice using the erythrocytes micronucleus test and the comet assay.

Açai, the fruit of a palm native to the Amazonian basin, is widely distributed in northern South America, where it has considerable economic importance. Whereas individual polyphenolics compounds in açai have been extensively evaluated, studies of the intact fruit and its biological properties are lacking. Therefore, the present study was undertaken to investigate the in vivo genotoxicity of açai and its possible antigenotoxicity on doxorubicin (DXR)-induced DNA damage. The açai pulp doses selected were 3.33, 10.0 and 16.67g/kg b.w. administered by gavage alone or prior to DXR (16mg/kg b.w.) administered by intraperitoneal injection. Swiss albino mice were distributed in eight groups for acute treatment with açai pulp (24h) and eight groups for subacute treatment (daily for 14 consecutive days) before euthanasia. The negative control groups were treated in a similar way. The results of chemical analysis suggested the presence of carotenoids, anthocyanins, phenolic, and flavonoids in açai pulp. The endpoints analyzed were micronucleus induction in bone marrow and peripheral blood cells polychromatic erythrocytes, and DNA damage in peripheral blood, liver and kidney cells assessed using the alkaline (pH >13) comet assay. There were no statistically significant differences (p>0.05) between the negative control and the groups treated with the three doses of açai pulp alone in all endpoints analyzed, demonstrating the absence of genotoxic effects. The protective effects of açai pulp were observed in both acute and subacute treatments, when administered prior to DXR. In general, subacute treatment provided greater efficiency in protecting against DXR-induced DNA damage in liver and kidney cells. These protective effects can be explained as the result of the phytochemicals present in açai pulp. These results will be applied to the developmental of food with functional characteristics, as well as to explore the characteristics of açai as a health promoter.

Resveratrol attenuates cisplatin-induced nephrotoxicity in rats.

Cisplatin is an antitumor drug widely used in the treatment of many malignant tumors. However, the most common adverse effect, nephrotoxicity, limits the use of this drug in many cancer patients. Resveratrol is a phytoalexin that presents highly efficient protection in experimental nephrotoxicity models. This study evaluated the effect of resveratrol on cisplatin-induced kidney damage. Male Wistar rats were treated with resveratrol (25 mg/kg b.w., i.p.) before the administration of cisplatin (5 mg/kg b.w., i.p.) and killed 2 or 5 days later. Blood and urine samples were collected and the kidneys were removed. Rats from the cisplatin group showed acute tubular cell necrosis and increased immunostaining for ED1 (macrophages/monocytes) and T-lymphocytes in the renal cortex and outer medulla when compared with the control group. These alterations were less intense in animals pre-treated with resveratrol. Moreover, indicators of renal injury such as increased serum creatinine levels, urinary volume and urinary protein caused by the administration of cisplatin, were also significantly reduced with resveratrol. Increased lipid peroxidation and glutathione depletion in tissue were attenuated by resveratrol. In conclusion, resveratrol attenuated the cisplatin-induced structural and functional renal changes by reducing free radicals and inhibiting inflammatory cell infiltrates.