Joana Darc Castania Darin

Effects of the antioxidants curcumin and vitamin C on cisplatin-induced clastogenesis in Wistar rat bone marrow cells.

The use of dietary antioxidants to prevent antitumor agent-induced chromosomal damage in nontumor cells is currently eliciting considerable interest. Curcumin (CMN) is a dietary antioxidant that has been reported to protect against clastogenesis in in vivo and in vitro assays. This study was undertaken to investigate the modulatory effects of CMN on cisplatin-induced chromosomal aberrations in Wistar rat bone marrow cells and whether there is any potentiation of these effects with the combination between CMN and vitamin C (VC), which has been reported to reduce the clastogenic effect of many antitumor agents in in vivo assays. Animals treated with CMN plus a single dose of cisplatin, at 18, 24 or 72 h following treatment, presented a statistically significant reduction in the total amount of chromosomal damage and in the number of abnormal metaphases. The results also indicate that the combination between antioxidants would not be effective in protecting against cisplatin-induced chromosomal damage in animals sacrificed 24 h after cisplatin treatment. Under the present experimental conditions, CMN could prevent cisplatin-induced clastogenesis by acting as a free radical scavenger.

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.

Anticlastogenic effect of vitamin C on cisplatin in vivo

Neste estudo foi avaliado o efeito protetor da vitamina C (VC) sobre a acao clastogenica da cisplatina (DDP) em celulas da medula ossea de ratos. A DDP, um agente quimioterapico, foi injetada em ratos Wistar sozinha ou apos o tratamento com a VC. Os animais foram tratados com VC (50, 100 or 200 mg/kg de peso corporal) por gavagem 10 min antes da administracao intraperitoneal de DDP (5 mg/kg de peso corporal). Os resultados obtidos mostraram que a VC foi efetiva na reducao estatisticamente significativa da clastogenicidade da DDP em ratos Wistar (aproximadamente 70%). O efeito antioxidante da VC foi proposto para explicar a modulacao da acao clastogenica da DDP.

Evaluation of the antihypertensive properties of yellow passion fruit pulp (Passiflora edulis Sims f. flavicarpa Deg.) in spontaneously hypertensive rats.

Various species of the genus Passiflora have been extensively used in traditional medicine as sedatives, anxiolytics, diuretics and analgesics. In the present study, after the identification and quantification of phytochemical compounds from yellow passion fruit pulp by liquid chromatography‐photodiode array‐mass spectrometry (HPLC‐PDA‐MS/MS), its antihypertensive effect was investigated on spontaneously hypertensive rats. Additionally, the renal function, evaluated by kidney/body weight, serum creatinine, proteinuria, urinary flow, reduced glutathione (GSH) levels and thiobarbituric acid‐reactive substances (TBARS) and mutagenicity in bone marrow cells were assessed to evaluate the safety of passion fruit consumption. Yellow passion fruit pulp (5, 6 or 8 g/kg b.w.) was administered by gavage once a day for 5 consecutive days. HLPC‐PDA‐MS/MS analysis revealed that yellow passion fruit pulp contains phenolic compounds, ascorbic acid, carotenoids and flavonoids. The highest dose of passion fruit pulp significantly reduced the systolic blood pressure, increased the GSH levels and decreased TBARS. There were no changes in renal function parameters or the frequency of micronuclei in bone marrow cells. In conclusion, the antihypertensive effect of yellow passion fruit pulp, at least in part, might be due to the enhancement of the antioxidant status. The exact mechanisms responsible by this effect need further investigation. Copyright

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 β-caryophyllene. Thus, it can be assumed that the oil resin and volatile and resinous fractions from the commercial product are not genotoxic or mutagenic.

Effects of selenium pretreatment on cisplatin‐induced chromosome aberrations in Wistar rats

Selenium is an essential trace element and a potent anticancer agent. Extensive laboratory studies demonstrate that selenium is an effective chemopreventive agent in various sites in animals. The administration of selenium as a chemopreventive agent raises the question whether the antioxidant selenium, alone or in combination with other dietary antioxidants, could protect non-tumor cells from the clastogenic effect of cisplatin. Therefore, the present study was undertaken to investigate the modulatory effects of selenium, combined or not with vitamin C, on cisplatin-induced chromosomal aberrations in Wistar rat bone marrow cells. The animals were sacrificed 18, 24, or 72 h after cisplatin injection. The results obtained in Wistar rat bone marrow cells showed a slight nonsignificant reduction in the total number of chromosomal aberrations induced by cisplatin (5 mg/kg b.w.) observed in the animals that received a pretreatment with a single dose of selenium (2 mg/kg b.w.). The administration of two doses of selenium (1 mg/kg b.w.) also did not inhibit the chromosomal damage induced by cisplatin. In the present study, no protective response was obtained with either a single or double dose of selenium in rats treated with cisplatin. Furthermore, the combination between selenium+vitamin C was no more effective than vitamin C alone in the protection against damage caused by this antitumor drug. Further investigations, with other forms of selenium, are necessary to elucidate a possible protective role of selenium in clastogenicity induced by free radicals generated by antitumor drugs.

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.

Effects of maternal vitamin B6 deficiency and over-supplementation on DNA damage and oxidative stress in rat dams and their offspring

Vitamin B6 is a cofactor for more than 140 essential enzymes and plays an important role in maternal health and fetal development. The goal of this study was to investigate the effects of maternal vitamin B6 on DNA damage and oxidative stress status in rat dams and their offspring. Female Wistar rats were randomly assigned to three dietary groups fed a standard diet (control diet), a diet supplemented with 30 mg/kg of vitamin B6, or a deficient diet (0 mg/kg of vitamin B6) for 10 weeks before and during mating, pregnancy and lactation. The dams were euthanized at weaning, and their male pups were euthanized either 10 days or 100 days after birth. We found that maternal vitamin B6 deficiency increased the micronucleus frequency in peripheral blood and bone marrow cells and also increased the concentration of hepatic TBARS (thiobarbituric acid reactive substances) in newborn pups (10 days old). In conclusion, maternal 5- to 6-fold over-supplementation of vitamin B6 had no adverse effects, however its deficiency may induce chromosomal damage and hepatic lipid peroxidation in the offspring.

Genotoxicity and antigenotoxicity of Caryocar villosum in rats tissues evaluated by the comet assay and micronucleus test

f 15% was observed, whereas in June PM-2.5 was reduced by 83% uncorrected). In February (but not in June) total volatile organic ompounds (corrected for outdoor values) were reduced by 82% n weekend days and 57% on schooldays. No significant influence f the PATUs on the air concentrations of formaldehyde, NO2, O3 nd molds was observed. During teaching hours on schooldays the ATUs appeared to perform worse than on undisturbed weekend ays. Our study showed that air treatment devices should be tested n real-life settings to evaluate their influence on health-related ndicators of indoor air quality.