Can Spirulina maxima reduce the mutagenic potential of sibutramine?

The worldwide obesity pandemic requires the use of anti-obesity drugs. Sibutramine is an anti-obesity drug that has been used worldwide but is indiscriminately consumed in Brazil. Several studies have demonstrated that sibutramine promotes weight loss and weight maintenance, but several side effects have been associated with its systematic consumption. For this reason, sibutramine was withdrawn from the European and American markets, but still remains legal for use in Brazil. Studies have shown that a 5-10% reduction in body weight results in outstanding health benefits for obese patients. However, in order to promote significant weight loss, it is necessary to use sibutramine for at least 2 years. This long-term exposure has carcinogenic potential, as sibutramine causes DNA damage. Thus, this study evaluated the in vivo mutagenic potential of sibutramine alone (5, 7, 10, 15, and 20 mg/kg) and in association with Spirulina maxima (150 and 300 mg/kg), a cyanobacterium with antioxidant potential, using the polychromatic erythrocyte micronucleus test. Our results reinforced the mutagenic potential of sibutramine alone, which showed a time-dependent action. Combinatory treatments with S. maxima were not able to reduce the genotoxicity of sibutramine. These results were confirmed in vitro with the cytokinesis-blocked micronucleus test. In conclusion, our data showed that new alternative anti-obesity treatments are needed since the consumption of sibutramine can increase the risk of cancer in overweight patients.

Mutagenic potential of Cordia ecalyculata alone and in association with Spirulina maxima for their evaluation as candidate anti-obesity drugs.

Obesity is one of the most important nutritional disorders, and can be currently considered as an epidemic. Although there are few weight reduction drugs available on the market, some new drug candidates have been proposed, including Cordia ecalyculata, a Brazilian plant with anorectic properties, and Spirulina maxima, a cyanobacterium with antioxidant and anti-genotoxic activity. In this study, we evaluated the mutagenic potential of C. ecalyculata at doses of 150, 300, and 500 mg/kg alone and in association with S. maxima at doses of 75, 150, and 250 mg/kg, respectively, through an in vivo micronucleus test, using mice of both sexes, and an in vitro micronucleus test and comet assay, using human peripheral blood. For all tests, cyclophosphamide was used as a positive control. The results showed that treatment of 300 mg/kg C. ecalyculata and the combination treatment of 500 mg/kg C. ecalyculata with 250 mg/kg S. maxima resulted in anorectic effects. The mutagenic tests did not reveal any clastogenic or genotoxic activity for any treatment, indicating that these candidates could be marketed as weight-reduction drugs. Moreover, the drugs contain chemo-preventive substances that can protect against tumorigenesis, which has been associated with obesity.

Carnitine partially improves oxidative stress, acrosome integrity, and reproductive competence in doxorubicin-treated rats.

Doxorubicin has been largely used in anticancer therapy in adults, adolescents, and children. The efficacy of l-carnitine as an antioxidant substance has been confirmed both in humans and rats. Carnitine, present in testis and epididymis, is involved in sperm maturation. It is also effective in infertility treatment. As a continuation of a previous study, we evaluated whether some spermatic qualitative parameters, DNA integrity, chromatin structure, and fertility status, could be ameliorated by the carnitine treatment in adult rats, which were subsequently exposed to doxorubicin at pre-puberty. Pre-pubertal male rats were distributed into four groups: Sham Control; Doxorubicin; l-carnitine; l-carnitine + Doxorubicin (l-carnitine injected 1 h before doxorubicin). At 100 days of age, all groups were reassigned into two sets: One set was submitted to the evaluation of sperm motility, acrosome integrity, mitochondrial activity, sperm chromatin structure analysis (SCSA), and evaluation of the oxidative stress. The other set of rats was destined to the evaluation of reproductive competence. The percentage of spermatozoa with intact acrosome integrity was higher in the Carnitine+Doxorubicin group when compared with the Doxorubicin group. However, sperm motility and mitochondrial activity were not improved by carnitine pre-treatment. Both values of malondialdehyde and nitrite (indirect measurement of nitric oxide) concentrations were statistically higher in the only doxorubicin-treated group when compared to the Carnitine + Doxorubicin group. Fertility index and implantation rate were lower in Doxorubicin group, when compared to Carnitine + Doxorubicin group. Moreover, the percentage of spermatozoa with damaged DNA was higher in the Doxorubicin-treated group when compared to the Carnitine+Doxorubicin group. l-carnitine, when administered before doxorubicin, partially preserved the acrosome integrity, an important feature related to sperm fertilization ability that positively correlated with the reproductive competence and sperm DNA integrity at adulthood. In conclusion, l-carnitine attenuated the long-term alterations caused by doxorubicin in the germ cells and improved male reproductive capacity in adulthood.