Mutagenic Evaluation of Fluoxetine and Fluoxetine-Galactomannan Complex Through the Analysis of Chromosomal Aberrations in Human Peripheral Leukocytes and Salmonella typhimurium/Microssome Assay / Avaliação Mutagênica de Fluoxetina e Complexo Fluoxetina-Galactomanana Através da Análise de Aberrações Cromossômicas em Leucócitos Periféricos Humanos e em Salmonella typhimurium / Ensaio Microssômico

Objectives: The purpose of this study was to evaluate the mutagenic potential of fluoxetine and fluoxetine-galactomannan. Methods: Chromosomal aberration test and Salmonella typhimurium/microsome mutagenicity assay. Results: The results showed that fluoxetine (250 µg/mL) can cause chromosomal breaks of treated leukocytes and increase the frequency of reversion of the tester strains of S. typhimurium / microsome assay only at the highest concentration (5 mg/mL), while fluoxetine encapsulated in galactomannan did not cause these changes (leukocytes and S. typhimuriums strains). Conclusion: In summary, fluoxetine showed a mutagenic effect detectable only at high concentrations in both eukaryotic and prokaryotic models. Furthermore, the fluoxetine/galactomannan complex, in this first moment, prevented the mutagenicity attributed to fluoxetine, emphasizing that the present encapsulation process can be an alternative in preventing these effects in vitro.

Objetivos: avaliar o potencial mutagênico da fluoxetina e da fluoxetina-galactomanana. Métodos: Teste de aberração cromossômica e ensaio de mutagenicidade de Salmonella typhimurium /microssoma. Resultados: a fluoxetina (250 µg/mL) pode causar quebras cromossômicas de leucócitos tratados e aumentar a frequência de reversão das cepas testadoras de S. typhimurium /microssoma apenas na concentração mais alta (5 mg/mL), enquanto a fluoxetina encapsulada em galactomanano não causou essas alterações (leucócitos e cepas de S. typhimurium). Conclusão: a fluoxetina mostrou um efeito mutagênico detectável apenas em altas concentrações em modelos eucarióticos e procarióticos. Além disso, o complexo fluoxetina/galactomanan, neste primeiro momento, evitou a mutagenicidade atribuída à fluoxetina, ressaltando que o presente processo de encapsulamento pode ser uma alternativa na prevenção desses efeitos in vitro.

Antimutagenic activity of cashew apple (Anacardium occidentale Sapindales, Anacardiaceae) fresh juice and processed juice (cajuína) against methyl methanesulfonate, 4-nitroquinoline N-oxide and benzo[a]pyrene

Cashew apple juice (CAJ), produced from the native Brazilian cashew tree (Anacardium occidentale), and has been reported to have antibacterial, antifungal, antitumor, antioxidant and antimutagenic properties. Both the fresh unprocessed juice and the processed juice (cajuína in Portuguese) has been shown to consist of a complex mixture containing high concentrations of anacardic and ascorbic acids plus several carotenoids, phenolic compounds and metals. We assessed both types of juice for their antimutagenic properties against the direct mutagens methyl methanesulfonate (MMS) and 4-nitroquinoline-N-oxide (4-NQO) and the indirect mutagen benzo[a]pyrene (BaP) using pre-treatment, co-treatment and post-treatment assays with Salmonella typhimurium strains TA100, TA102, and TA97a. In pre-treatment experiments with strains TA100 and TA102 the fresh juice showed high antimutagenic activity against MMS but, conversely, co-treatment with both juices enhanced MMS mutagenicity and there was an indication of toxicity in the post-treatment regime. In pre-, co-, and post-treatments with TA97a as test strain, antimutagenic effects were also observed against 4-NQO and BaP. These results suggest that both fresh and processed CAJ can protect the cells against mutagenesis induced by direct and indirect mutagens.

Cytogenetic and genotoxic effects of the insecticides, imidacloprid and methamidophos

We examined the cytogenetic and genotoxic effects of the neonicotinoid insecticide imidacloprid and the organophosphate insecticide methamidophos, when administered alone or in combination. These insecticides were tested with the bone marrow chromosome aberration assay and micronucleus test in rats and by the bacterial mutation assay (Salmonella/microsome mutagenicity assay). Wistar albino rats were orally fed daily with laboratory chow treated with various concentrations of insecticides, 50 and 100 mg/kg imidacloprid, 2.5 and 5 mg/kg methamidophos, and 2.5 and 5 mg/kg imidacloprid plus methamidophos, respectively, for 90 days. Numerical and structural chromosomal aberrations were evaluated. Significant differences were detected between all the insecticide-administered groups versus the control group and between the two concentrations of the pesticide-treated groups. Both concentrations of the insecticides induced a dose-related increase in the micronucleus frequency (P < 0.05). Dose-related increases in the number of revertants were observed with the two Salmonella strains (TA98 and TA100). All tested doses of the insecticides demonstrated mutagenic activity in the presence of S9 mix. These results lead us to the conclusion that the synergistic effect of methamidophos and imidacloprid causes an increase in potential damage to non-target organisms.

Antimutagenicity of 14 Compounds in Salmonella typhimurium TA100 / 第二军医大学学报

The antimutagenicity of 14 compounds, cysteine (1), cinnamic acid (2), rutin (3), tannic acid (4), germanium dioxide (5),fluoro uracil (6), sodium copper chlorophylline (7),?-sitosterol (8), vitamin C (9), coumarin (10), vitamin E (11), L-glutathine (oxidized form) (12), L-glutathine (reduced form) (13) and organic germanium (14), were investigated using Salmonella typhimurium/microsome assay in TA100.Three modes of action, i.e. inhibitory, antimutagenic and desmutagenic effects, were observed-for their antimutagenicity. Results showed that all of test compounds inhibited mutagenicity induced by MNNG and B(a)P with the exception of germanium dioxide. Percent inhibition of compounds 1, 2, 3, 4, 6, 8, 10 and 12 were greater than 90%. 14 compounds exhibited antimutagenic effects on the mutagenic activity of MNNG, and 12 compounds exhibited antimutagenic effects on B(a)P. Germanium dioxide and organic germanium had no such effect. 14 compounds all exerted desmutagenic effects on B (a)P directly before B(a)P acted on cells. According to the potential and modes of action, cysteine, cinnamic acid, rutin, tannic acid and coumarin were better among 14 compounds. The doseresponse relationships of inhibitory and antimutagenic effects on mutation induced by MNNG and B(a)P were found. Each compound has its sufficient range of dosage. These studies suggest that it is necessary to select effective antimutagens to make mixtures, and their synergistic effects should be investigated.