In vivo evaluation of the antimutagenic and antigenotoxic effects of ß-glucan extracted from Saccharomyces cerevisiae in acute treatment with multiple doses.

Ample evidence suggests that cancer is triggered by mutagenic damage and diets or supplements capable of reducing such incidences can be related to the prevention of neoplasy development or to an improvement in life quality of patients who undergo chemotherapy. This research aimed to evaluate the antimutagenic and antigenotoxic activity of ß-glucan. We set up 8 experimental groups: control (Group 1), cyclophosphamide (Group 2), Groups 3-5 to assess the effect of ß-glucan administration, and Groups 6-8 to evaluate the association between cyclophosphamide and ß-glucan. The intraperitonial concentrations of ß-glucan used were 100, 150 and 200 mg/kg. Micronucleus and comet assays showed that within the first week of treatment ß-glucan presented a damage reduction rate between 100-62.04% and 94.34-59.52% for mutagenic and genotoxic damages, respectively. This activity decreased as the treatment was extended. During the sixth week of treatment antimutagenicity rates were reduced to 59.51-39.83% and antigenotoxicity was not effective. This leads to the conclusion that the efficacy of ß-glucan in preventing DNA damage is limited when treatment is extended, and that its use as a chemotherapeutic adjuvant need to be better clarified.

Chlorophyllin in the intra-uterine development of mice exposed or not to cyclophosphamide / Clorofilina no desenvolvimento intra-uterino de camundongos expostos ou não à ciclofosfamida

Chlorophyllin, a sodium-copper salt synthesized from chlorophyll, has already proved to have anticlastogenic, antimutagenic and anticarcinogenic activity, however few are the studies in the teratogenicity area. The present study evaluated the effects of chlorophyllin in intra- uterine development of mice exposed or not to cyclophosphamide. Pregnant females were divided into 8 groups of 15 animals each, G01 - PBS (0.1 mL 10.0-1 g) orally; G02 ­ cyclophosphamide (20.0 mg kg-1) i.p.; G03, G04 and G05 - chlorophyllin at concentrations of (5.0, 10.0 and 15.0 mg kg-1) orally; G06, G07 and G08 (5.0, 10.0 and 15.0 mg kg -1) orally, of chlorophyllin, respectively, and (20.0 mg kg-1) i.p. of cyclophosphamide. In the 18th day the females were submitted to laparotomy and females and fetuses analyzed. The results showed that the chlorophyllin was not effective in protecting the reproductive parameters as well as teratogenicity. Finally, it was observed that the presence of chlorophyllin increased the frequency of some malformations when combined with cyclophosphamide. However, it was not teratogenic and not embryo lethal in this experimental design.

Clorofilina é um sal de cobre e sódio sintetizado a partir da clorofila. Provou-se ter atividade anticlastogênica, antimutagênica e anticarcinogênica. No entanto, poucos são os estudos sobre esta substância na área de teratologia. Dessa forma, o presente trabalho avaliou os efeitos da clorofilina no desenvolvimento intrauterino de camundongos expostos ou não à ciclofosfamida. Para tal, fêmeas prenhez foram divididas em oito grupos experimentais contendo 15 animais cada: G01 - PBS (0,1 mL 10.0-1 g) via oral; G02 - ciclofosfamida (20,0 mg kg-1), intraperitoneal; G03, G04 e G05 - clorofilina em concentrações de (5,0; 10,0 e 15,0 mg kg-1) via oral; G06, G07 e G08 (5,0, 10,0 e 15,0 mg kg-1) via oral, de clorofilina, respectivamente, e 20,0 mg kg-1, via intraperitoneal, de ciclofosfamida. No 18º dia de gestação, os animais foram submetidos à laparotomia e os fetos, analisados para parâmetros teratogênicos. Os resultados mostraram que a clorofilina não foi eficaz para proteger os parâmetros reprodutivos, bem como a teratogenicidade. Finalmente, foi observado que a clorofilina quando combinada com a ciclofosfamida aumentou a frequência de algumas malformações. No entanto, a clorofilina não se apresentou teratogênica e nem letal para este desenho experimental.

Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice / Os efeitos tóxicos de diferentes doses de ciclofosfamida nos parâmetros reprodutivos de camundongos machos

The cyclophosphamide is used in cancer treatment. The aim of this study was evaluating the effect of different doses of this drug on male mice reproductive parameters. The cyclophosphamide was administered in the doses 100, 150, 200 e 250 mg.kg-1, intraperitoneal route, for six weeks. As a result, it was observed a decrease in body mass and a decrease in testicles and kidney's weight, in all animals treated with cyclophosphamide. Only the groups that received the doses 100, 150 mg.kg-1 of cyclophosphamide were able to fertilize their females. There was higher incidence of post- implantation losses, reabsorptions and decrease in fetal viability in the group that received the dose of 150 mg.kg-1. It was observed a reduction in epididymis and liver's weight of the animals treated with the doses 150, 200 e 250 mg.kg-1. Abnormal spermatozoa were found in the doses 200 e 250 mg.kg-1. Based on the methodology used and results obtained, it was concluded that the cyclophosphamide was toxic, considering the decrease in animal's body mass and testicle's weight; promoted hepatotoxicity and nephrotoxic effect; influenced in the animals spermatogenesis taking them to infertility and/or subfertility; decreased fetal viability, despite it didn't cause significant malformations in the offspring.

A ciclofosfamida é utilizada no tratamento de câncer. Este estudo visa avaliar os efeitos das diferentes doses do fármaco nos parâmetros reprodutivos de camundongos machos. A ciclofosfamida foi administrada nas doses de 100, 150, 200 e 250 mg kg-1, via intraperitoneal por seis semanas. Como resultado observou-se diminuição de massa corporal, redução no peso de testículos e rins em todos os animais tratados com a ciclofosfamida. Apenas os grupos que receberam as doses de 100 e 150 mg kg-1 do quimioterápico foram capazes de fertilizar as fêmeas. Houve maior incidência de perdas pós-implantação, reabsorção e diminuição da viabilidade fetal no grupo que recebeu a dose de 150 mg kg-1. Observou-se redução nos pesos dos epidídimos e fígado dos animais tratados com as doses de 150, 200 e 250 mg kg-1. Espermatozóides anômalos foram encontrados nas doses de 200 e 250mg kg-1. Com base na metodologia empregada e nos resultados obtidos, conclui-se que a ciclofosfamida foi tóxica considerando-se a redução de massa corporal e o peso dos testículos dos animais; promoveu hepatotoxicidade e efeito nefrotóxico; influenciou na espermatogênese dos animais de forma a levá-los a um estado de infertilidade e/ou subfertilidade; diminuiu viabilidade fetal, entretanto não causou malformações significativas na prole.

Effects of the polysaccharide beta-glucan on clastogenicity and teratogenicity caused by acute exposure to cyclophosphamide in mice.

Alterations that could lead to the cancer development may also be related to an adverse development of offspring in experimental animals. Some functional foods, which contain the polysaccharide beta-glucan, have been described as being effective in the prevention of clastogenic damage. Based on that finding, the aim of the present study was to determine the efficacy of this sugar polymer in the mutagenic and teratogenic damage control. Two sets of females, pregnant and non-pregnant, were evaluated. The results indicated that beta-glucan was effective in preventing clastogenic damage in pregnant as well as non-pregnant females. In addition, pregnant females were more susceptible to mutagenic damage. However, teratogenic effects were not prevented effectively, although there was a trend toward a reduction in level of malformations. Despite beta-glucan did not prevent malformations, it increased fetal viability and reduced number of post-implantation losses and resorption, thereby enhancing reproductive performance in females.