Lusânia Maria Greggi Antunes

Radicais livres e os principais antioxidantes da dieta

During the reduction of molecular oxygen, reactive oxygen species are formed and there is a continuous requirement for inactivation of these free radicals. Damage induced by free radicals can affect many biological molecules, including lipids, proteins, carbohydrates and vitamins present in the food. Reactive oxygen species are also thought to be implicated in the pathogenesis of various human diseases. In fact, evidence has been accumulated indicating that a diet rich in antioxidants reduce the risks of the major human diseases. This review discusses the importance of dietary antioxidants in the defense strategies of organisms against free radicals.

The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats

The antioxidant activity of the amino acid glutamine was investigated to obtain protection against peroxidative damage in rat kidney and nephrotoxicity induced by the treatment with a single dose of the antitumoral cisplatin (5mgkg(-1) body weight). The animals were divided into four treatment and control groups of six rats each (n=6). Cisplatin was injected i.p. and glutamine (300mgkg(-1) body weight) was given by gavage 24h before the cisplatin injection. After 24h and 7 days of cisplatin administration, the rats were sacrificed. A single dose of cisplatin resulted in significant reduction in body weight and creatinine clearance, and higher urinary volumes were observed in all groups treated with this antitumor drug (P<0.05). Renal tissue from cisplatin-treated rats showed an increase in malondialdehyde production and increase in glutathione contents 24h and 7 days after cisplatin administration. Pretreatment of rats with glutamine substantially inhibited the increase in the levels of renal glutathione induced by cisplatin 24h after the i.p. injection. The malondialdehyde in the renal tissues was significantly reduced 7 days after cisplatin treatment. However, the reduction in the peroxidative damage did not reach the value of the control group. The protective effects obtained by glutamine pretreatment in peroxidative alterations were not observed in the other parameters studied. These results suggest that glutamine partially protect against cisplatin-induced lipid peroxidation damage, but it was not enough to inhibit cisplatin-induced nephrotoxicity in rats.

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.

Effects of high doses of vitamins C and E against doxorubicin-induced chromosomal damage in Wistar rat bone marrow cells

Doxorubicin (DXR) is one of the major antitumoral agents available for clinical use. In addition to intercalating into the DNA molecule, this drug generates free radicals. Vitamins C (VC) and E (VE) can protect normal cells from the damage caused by radicals without interfering with the cytotoxicity of DXR against tumors. The objective of the present study was to investigate the possible protective effect of VC and/or VE on mammalian cells treated with DXR in vivo. Animals treated with the lowest doses of VC and/or VE, alone or in combination, plus a single dose of DXR presented a statistically significant reduction in total number of chromosome aberrations and in number of abnormal metaphases. The highest vitamin doses tested caused no changes in the parameters analyzed when compared with control. Under the present experimental conditions, the efficiency of VC and/or VE in protecting against chromosome damage was dependent on the dose used.

Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells.

Engineered nanomaterials have been extensively applied as active materials for technological applications. Since the impact of these nanomaterials on health and environment remains undefined, research on their possible toxic effects has attracted considerable attention. It is known that in humans, for example, the primary site of gold nanoparticles (AuNps) accumulation is the liver. The latter has motivated research regarding the use of AuNps for cancer therapy, since specific organs can be target upon appropriate functionalization of specific nanoparticles. In this study, we investigate the geno and cytotoxicity of two types of AuNps against human hepatocellular carcinoma cells (HepG2) and peripheral blood mononuclear cells (PBMC) from healthy human volunteers. The cells were incubated in the presence of different concentrations of AuNps capped with either sodium citrate or polyamidoamine dendrimers (PAMAM). Our results suggest that both types of AuNps interact with HepG2 cells and PBMC and may exhibit in vitro geno and cytotoxicity even at very low concentrations. In addition, the PBMC were less sensitive to DNA damage toxicity effects than cancer HepG2 cells upon exposure to AuNps.

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.

Protective effects of the amino acid glutamine and of ascorbic acid against chromosomal damage induced by doxorubicin in mammalian cells.

The interaction of antioxidants can provide an essential protection against the damaging effects of free radicals. Beneficial interactions include radioprotection, protection against acute toxicity of chemicals, and antimutagenic and anticarcinogenic activity. The present study was undertaken to evaluate the protective effect of the amino acid glutamine (GLN) and ascorbic acid (AA) on the frequency of chromosomal aberrations induced by the antineoplastic agent doxorubicin (DXR). These micronutrients were tested separately and simultaneously in Wistar rat bone marrow and Chinese hamster ovary (CHO) cells. The treatments with GLN and/or AA significantly decreased the frequency of DXR-induced clastogenic damage in both test systems.

Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells

The potential neuroprotective benefits of curcumin against cisplatin neurotoxicity were investigated. Curcumin is a polyphenol derived from the rhizome of Curcuma longa whose pharmacological effects include antioxidant, anti-inflammatory and anti-cancer properties. Cisplatin is a potent chemotherapeutic drug with activity against a wide variety of tumors, although it has notorious side effects. Cisplatin neurotoxicity is clinically evident in patients that have undergone a full course of chemotherapy and develop a peripheral neuropathy that may affect the treatment regimen and the patients qualify of life. In this study, we examined whether curcumin can protect against cisplatin neurite outgrowth inhibition in PC12 cells, which is an indicator of the protective potential against neuropathy. We also investigated whether curcumin affects cisplatin effectiveness by analyzing the modulation of p53 gene expression and its effect on cisplatin cytotoxicity in HepG2 tumor cells. Non-cytotoxic concentrations of curcumin reduced in vitro neurotoxicity of cisplatin in PC12 cells. The treatment of PC12 cells with cisplatin (10μg/mL) significantly reduced neurite outgrowth. The tested concentration of curcumin (1.0 and 10μg/mL) did not result in neurite toxicity but nevertheless diminished cisplatin-induced inhibition of neurite outgrowth by up to 50% (p<0.05). Our results indicate that curcumin does not compromise cisplatins anticancer activity. Curcumin neither suppressed p53 mRNA transcription nor protected tumor cells against cisplatin cytotoxicity. These results indicate that curcumin may reduce cisplatin-induced neurotoxicity, and clinical studies should potentially be considered.

Mutagenicity and antimutagenicity of the main food colorings

Many compounds present in foods, whether natural or added or produced during processing, have already been tested for mutagenicity or antimutagenicity in different experimental systems. The great number of food colorings available, both natural and synthetic, has led researchers to assess the mutagenicity and/or antimutagenicity of these compounds. Some synthetic colorings have mutagenic potential and their use has been forbidden in some countries. Many natural colorings tested have antimutagenic potential in at least one test system, but this does not mean that natural dyes are innocuous. The natural coloring curcumin, for example, showed antimutagenic potential in in vivo tests but was mutagenic in in vitro tests. This paradox emphasizes the importance of careful assessment and wide investigation into the possible mutagenic and/or antimutagenic activity of food colorings.

Protection and induction of chromosomal damage by vitamin C in human lymphocyte cultures.

Some chemotherapeutic approaches have proposed the use of antioxidants such as vitamin C (VC) to minimize the cytotoxicity and damage induced in normal tissue by antitumor agents that produce free radicals. Nevertheless, VC can also be cytotoxic, genotoxic, and harmful when combined with antitumor agents in human cells in vitro. The present study was undertaken to investigate the effects of VC (100, 200, 500, and 1,000 microg/ml) on human peripheral blood lymphocytes in vitro and its anticlastogenic effect on chromosomal aberrations induced by doxorubicin (DXR). VC did not show a clastogenic effect by itself, except at 1,000 microg/ml. At the concentration of 100 or 200 microg/ml of VC, administered in pre-, post-, or simultaneous treatment, there was a significant reduction in both chromosome aberrations and number of abnormal metaphases induced by DXR. At the doses of 500 or 1,000 microg/ml, VC did not present the same protective effect and was cytotoxic. Under the present experimental conditions, the efficiency of VC in protecting against chromosome damage was dependent on the doses used.