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Air pollution toxic effects are mainly attributed to small inhalable particulates with an aerodynamic diameter of less than 2.5 µm (PM 2.5). Our objective was to investigate mutagenic and clastogenic activity in PM samples collected in Rio de Janeiro. Samples were collected using a high-volume sampler at three sites: with low traffic and (2) and (3) with a heavy traffic. Six polycyclic aromatic hydrocarbons (PAHs) were quantified by gas chromatography/mass spectrometry (GC/MS). Salmonella typhimurium TA98 and the derivative strains YG1021 and YG1024 were used in mutagenicity assays in the presence of organic extracts (10–50 µg/ plate) with and without exogenous metabolization. Allium cepa test was performed to evaluate possible cytotoxic and clastogenic activities. The highest PM 2.5 µm (132.73 µm/m3) and PAH values (1.22 ng/m3 for benzo(a)pyrene) were detected at site 3. High mutagenic frameshift responses in absence and presence of metabolic activation were detected at site 3. The participation of nitroarenes and dinitroarenes was detected in the total mutagenicity of the extracts studied. The cytotoxic effect and the abnormalities detected by Allium cepa test can be attributed to the PAH nitroderivatives in the organic extracts. Evaluation of the genotoxicity of urban airborne particulate matter is important as a basis for decision making by regulatory authorities.

Nitrosamines are stable compounds, biologically and chemically inert unless activated. In biological systems, N-nitrosodiethylamine (NDEA) can be activated by a variety of enzymes, leading to aldehydes and/or intermediates which are themselves alkylating agents. Additionally, it has been shown that NDEA causes reactive oxygen species (ROS) production and induces mutagenicity. The cell defense seeks to neutralize ROS that escape the primary defense mechanisms (antioxidants) by DNA-repair mechanisms. NDEA is present at low concentrations in major dietary sources, like cured meats, salami, millet flour, and dried cuttlefish, where NDEA mutagenicity has been detected. These facts lead us to evaluate vitamin E as a ROS scavenger, in Escherichia coli mutants system, against genotoxicity induced by NDEA at low concentrations under exogenous metabolic activation. Statistical analysis were performed in order to compare the effects of NDEA-induced genotoxicity (a) between the mutants and the wild-type strains, at the same metabolic activation conditions and, (b) between the same strains in the presence or in the absence of vitamin E (150 μM). The indirect evaluation of ROS production by NDEA metabolizing shows that vitamin E protects E. coli cells proficient or deficient in the DNA-repair genes from cytotoxic effects. Our results underscore the role of scavenger molecules such as vitamin E in the diet, avoiding lesions induced by NDEA at low concentrations, via ROS, that could be repaired by nucleotide excision repair and base excision repair proteins.

Background: Statins present a plethora of pleiotropic effects including anti-inflammatory and antimicrobial responses. A,α-difluorophenylacetamides, analogs of diclofenac, are potent pre-clinical anti-inflammatory non-steroidal drugs. Molecular hybridization based on the combination of pharmacophoric moieties has emerged as a strategy for the development of new candidates aiming to obtain multitarget ligands. Methods: Considering the anti-inflammatory activity of phenylacetamides and the potential microbicidal action of statins against obligate intracellular parasites, the objective of this work was to synthesize eight new hybrid compounds of α,α-difluorophenylacetamides with the moiety of statins and assess their phenotypic activity against in vitro models of Plasmodium falciparum and Trypanosoma cruzi infection besides exploring their genotoxicity safety profile. Results: None of the sodium salt compounds presented antiparasitic activity and two acetated compounds displayed mild anti-P. falciparum effect. Against T. cruzi, the acetate halogenated hybrids showed moderate effect against both parasite forms relevant for human infection. Despite the considerable trypanosomicidal activity, the brominated compound revealed a genotoxic profile impairing future in vivo testing. Conclusions: However, the chlorinated derivative was the most promising compound with chemical and biological profitable characteristics, without presenting genotoxicity in vitro, being eligible for further in vivo experiments.

The seed oil of Carapa guianensis (Aublet), a tree from the Meliaceae family commonly known as andiroba, is widely used in Brazilian traditional medicine because of its multiple curative properties against fever and rheumatism and as an anti-inflammatory agent, antibacterial agent, and insect repellant. Since there is no consensus on the best way to obtain the C. guianensis oil and due to its ethnomedicinal properties, the aim of the present research was to evaluate the chemical composition, free-radical scavenging activity, and mutagenic and genotoxicity properties of three C. guianensis oils obtained by different extraction methods. The phenolic contents were evaluated by spectrophotometry. Oil 1 was obtained by pressing the dried seeds at room temperature; oil 2 was obtained by autoclaving, drying, and pressing; oil 3 was obtained by Soxhlet extraction at 30–60°C using petroleum ether. The oil from each process presented differential yields, physicochemical properties, and phenolic contents. Oil 1 showed a higher scavenging activity against the DPPH radical when compared to oils 2 and 3, suggesting a significant antioxidant activity. All oils were shown to be cytotoxic to bacteria and to CHO-K1 and RAW264.7 cells. At noncytotoxic concentrations, oil 2 presented mutagenicity to Salmonella enterica serovar Typhimurium and induced micronuclei in both cell types. Under the same conditions, oil 3 also induced micronucleus formation. However, the present data demonstrated that oil 1, extracted without using high temperatures, was the safest for use as compared to the other two oils, not showing mutagenicity or micronucleus induction.

Sclerosing agents as zinc gluconate-based chemical sterilants (Infertile®) are used for chemical castration. This solution is injected into the animal testis, but there are not enough evidences of its safety profiles for the receivers. The present work aimed to establish the pharmacokinetics and toxicological activity of Infertile, using in vitro and in silico approaches. The evaluation at the endpoint showed effects in a dose-dependent manner. Since necrosis is potentially carcinogenic, the possible cell death mechanism could be apoptosis. Our data suggested that Infertile at 60 mM presented risk for animal health. Even though Infertile is a licensed product by the Brazilian Ministry of Agriculture, Livestock and Supply, it presented a high mutagenic potential. We suggest that the optimal dose must be less than 6 mM, once, at this concentration, no mutagenicity or genotoxicity was observed.

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, and this class of drugs has been studied as protective agents against DNA damages. Alkylating agents (AAs) are able to induce alkylation in macromolecules, causing DNA damage, as DNA methylation. Our objective was to evaluate atorvastatin (AVA) antimutagenic, cytoprotective, and antigenotoxic potentials against DNA lesions caused by AA. AVA chemopreventive ability was evaluated using antimutagenicity assays (Salmonella/microsome assay), cytotoxicity, cell cycle, and genotoxicity assays in HepG2 cells. The cells were cotreated with AVA and the AA methyl methanesulfonate (MMS) or cyclophosphamide (CPA). Our datum showed that AVA reduces the alkylation-mediated DNA damage in different in vitro experimental models. Cytoprotection of AVA at low doses (0.1–1.0 μM) was observed after 24 h of cotreatment with MMS or CPA at their LC50, causing an increase in HepG2 survival rates. After all, AVA at 10 μM and 25 μM had decreased effect in micronucleus formation in HepG2 cells and restored cell cycle alterations induced by MMS and CPA. This study supports the hypothesis that statins can be chemopreventive agents, acting as antimutagenic, antigenotoxic, and cytoprotective components, specifically against alkylating agents of DNA.

Background: Statins present a plethora of pleiotropic effects including anti-inflammatory and antimicrobial responses. A,α-difluorophenylacetamides, analogs of diclofenac, are potent pre-clinical anti-inflammatory non-steroidal drugs. Molecular hybridization based on the combination of pharmacophoric moieties has emerged as a strategy for the development of new candidates aiming to obtain multitarget ligands. Methods: Considering the anti-inflammatory activity of phenylacetamides and the potential microbicidal action of statins against obligate intracellular parasites, the objective of this work was to synthesize eight new hybrid compounds of α,α-difluorophenylacetamides with the moiety of statins and assess their phenotypic activity against in vitro models of Plasmodium falciparum and Trypanosoma cruzi infection besides exploring their genotoxicity safety profile. Results: None of the sodium salt compounds presented antiparasitic activity and two acetated compounds displayed mild anti-P. falciparum effect. Against T. cruzi, the acetate halogenated hybrids showed moderate effect against both parasite forms relevant for human infection. Despite the considerable trypanosomicidal activity, the brominated compound revealed a genotoxic profile impairing future in vivo testing. Conclusions: However, the chlorinated derivative was the most promising compound with chemical and biological profitable characteristics, without presenting genotoxicity in vitro, being eligible for further in vivo experiments.

Chagas disease is responsible for a large number of human infections and many are also at risk of infection. There is no effective drug for Chagas disease treatment. The Institute of Pharmaceutical Technology at Fiocruz, Brazil, has designed three nitro analogs of the nitroimidazole-thiadiazole, megazol: two triazole analogs PTAL 05-02 and PAMT 09 and a pyrazole analog PTAL 04-09. A set of Salmonella enterica serovar Typhimurium strains were used in the bacterial reverse mutation test (Ames test) to determine the mutagenicity and cytotoxicity of megazol and its nitro analogs. Megazol presented positive mutagenic activity at very low concentration, either with or without metabolic activation S9 mix. The mutagenic response of the analogs was detected at higher concentration than the lowest megazol concentration to yield mutagenic activity showing that new advances can be made to develop new analogs. The micronucleus test with rat macrophage cells was used in the genotoxic evaluation. The analogs were capable of inducing micronucleus formation and showed cytotoxic effects. PTAL 04-09 structural modifications might be better suitable for the design of promising new drugs candidate for Chagas’ disease treatment.