Synergistic Antigenotoxic and Antioxidant Action of Gum Arabic and Eugenol in Rat Liver Following Induction of Colorectal Carcinogenesis.

OBJECTIVE: Much research has been conducted to identify natural antioxidant and antimutagenic compounds capable of preventing, reverting or treating conditions caused by oxidative stress and genotoxicity. In this study we evaluated the effects of 10% gum arabic (GA) and eugenol (EUG) on hepatic oxidative stress and genotoxicity induced by dimethylhydrazine (DMH) in rats. METHODS: The prevention arm of the study included 4 control groups and 4 experimental groups. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the same period and for an additional 9 weeks, the animals received either water, 10% GA , EUG or 10% GA + EUG  by gavage. The treatment arm of the study included 4 control groups and 4 experimental groups. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the subsequent 9 weeks, the animals received either water, 10% GA, EUG or 10% GA + EUG  by gavage. Finally, the livers were harvested for histopathological study with HE, measurement of genotoxicity and oxidative stress. RESULT: Genotoxicity and oxidative stress were found to be significantly lower in Group XII (animals treated concomitantly with GA and EUG). This is the first study to observe the synergistic action of GA and EUG administered concomitantly in this scenario. CONCLUSION: Indicating a synergistic antigenotoxic and antioxidant effect on liver cells in rats with DMH-induced colorectal carcinogenesis.

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.

Antioxidant and Antigenotoxic Actions of Gum Arabic on the Intestinal Mucosa, Liver and Bone Marrow of Swiss Mice Submitted to Colorectal Carcinogenesis.

Colorectal carcinogenesis is characterized by oxidative stress and the formation of aberrant crypts in its initial stages. Gum arabic (GA) is a natural product with antioxidant properties, and, therefore, supposed antitumor action. The aim of this study was to evaluate the effects of GA on the formation of aberrant crypts, as well as the local, hepatic, and systemic genotoxicity and oxidative stress. We induced colorectal carcinogenesis in Swiss male mice, afterwards treated them with water, 2.5% GA or 5% GA via gavage for twelve weeks and then performed surgery in order to obtain samples to analysis (proximal and distal colon, liver, blood, and bone marrow). The number of aberrant crypts in the GA-treated animals was lower than in the control groups. Likewise, there was a decline of colonic, hepatic, and systemic genotoxicity and oxidative stress. These results reflect the antioxidant role of GA and may lead to the development of treatments that inhibit colorectal carcinogenesis.

Chemopreventive effect of troxerutin against hydrogen peroxide-induced oxidative stress in human leukocytes through modulation of glutathione-dependent enzymes.

Troxerutin is a natural flavonoid present abundantly in tea, coffee, olives, wheat, and a variety of fruits and vegetables. Due to its diverse pharmacological properties, this flavonoid has aroused interest for treatment of various diseases, and consequently prompted investigation into its toxicological characteristics. The aim of this study was to evaluate the genotoxic and mutagenic effects and chemoprotective activity attributed to troxerutin using human peripheral blood leukocytes (PBLs) through several well-established experimental protocols based upon different parameters. Data demonstrated that troxerutin (100 to 1000 µM) induced no marked cytotoxic effect on PBLs after 24 hr, and did not produce strand breaks and mutagenicity. Regarding chemoprevention, this flavonoid attenuated cytotoxicity, genotoxicity, and mutagenicity initiated by hydrogen peroxide (H2O2) in human PBLs. Further, troxerutin demonstrated no marked cytotoxic effect on PBLs and exerted a protective effect against oxidative stress induced by H2O2 through modulation of GSH-dependent enzymes.