Evaluation of teratogenicity and genotoxicity induced by kramecyne (KACY).

Kramecyne (KACY), a polymer isolated from Krameria cytisoides Cav, has anti-inflammatory, anti-nociceptive, anti-arthritic and anti-ulcerogenic properties. As a part of standard preclinical safety tests, the present study sought to determine potential developmental toxicity (in female rats) and genotoxicity (in male mice) of KACY. Pregnant female rats were divided into six groups: the negative control (vehicle), the positive control (250 mg/kg of acetylsalicylic acid (ASA)), and four experimental groups (50, 250, 500 and 1000 mg/kg of KACY). To evaluate genotoxicity by in vivo micronuclei (MN) and sister chromatid exchange (SCE) tests, male mice were divided into five groups: the negative control (vehicle), the positive control (1.5 and 2.5 mg/kg of doxorubicin for MN and SCE, respectively), and three experimental groups (50, 500 and 1000 mg/kg of KACY). All treatments were administered by oral gavage. A slight maternal toxicity was evidenced by lower weight gain for rats receiving 500 and 1000 mg/kg of KACY, but no fetal malformations were found. However, there were less live fetuses/litter and greater post-implantation loss/litter at these two doses. Manifestations of developmental toxicity were limited to a higher rate of skeletal alterations. The MN tests did not evidence genotoxicity or cytotoxicity. KACY caused a slightly but significantly increased frequency of SCE. Although KACY-treated rats had skeletal alterations, these apparently were not caused by a mechanism of genotoxicity. Furthermore, the same administration in adult male mice did not produce genotoxicity. Hence, KACY herein proved to be safe for rats during the period of organogenesis.

Antioxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum.

There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson's disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 µg/2 µL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.

Glycine decreases developmental damage induced by hyperglycaemia in mouse embryos.

Hyperglycaemia induces neural tube defects and growth retardation in cultured mouse and rat embryos. In this study the possibility that glycine could prevent hyperglycaemia-induced embryopathy was researched. Early somite mouse embryos were cultured in normal medium, hyperglycaemic medium (50 mmol L(-1) glucose), or with glycine (1 mmol L(-1)) supplementation of normal and hyperglycaemic rat serum for 48 h. The embryo growth and differentiation were determined to estimate developmental and congenital malformations as well as lipid peroxidation levels. Adding glycine to the control culture medium did not affect embryonic development. Whereas the amino acid protected against telencephalon dysmorphogenesis, the decreased DNA content and number of somites, and the morphological score affectation induced by the hyperglycaemic medium, it had no preventive effect on the retarded differentiation of the otic system. Moreover, it prevented the high hyperglycaemia-induced lipoperoxidation levels of embryonic tissues. Embryos were partially protected from the hyperglycaemia-induced teratogenesis due to the antioxidative effect of glycine. As no other mechanisms related to the antiglycation or other protective effects of glycine were examined, the mechanism whereby it acted as an antiteratogenic agent needs further study.

Chemoprotective effect of Spirulina (Arthrospira) against cyclophosphamide-induced mutagenicity in mice.

The aim of this study was to investigate the antimutagenic effects of Spirulina (SP) on male and female mice by the dominant lethal test using cyclophosphamide (CP) as a mutagen. Animals of both sex were given SP orally at 0, 200, 400 or 800 mg/kg body weight (b.w.) for 2 weeks prior to starting the CP treatment. CP was i.p. injected daily for 5 days at 40 mg/kg b.w. For the male-dominant lethal test, each male was caged with untreated females per week for 3 weeks. For the female-dominant lethal test the above doses and schedule treatments were used and treated females were caged for one week with untreated males (1-2). On days 13-15 after breeding was |started all the females were evaluated for incidence of pregnancy, total corpora lutea, total implants and pre- and post-implant losses. In the male-dominant lethal test, the CP induced pre- and post-implant losses in untreated females were inhibited at all SP doses. In the female-dominant lethal test only post-implantation losses were prevented at the same doses. Semen examination of a separate group of mice showed that SP improved its quality. Our results illustrate protective effects of SP in relation to CP-induced genetic damage to germ cells.

Sister-chromatid exchange induction produced by in vivo and in vitro exposure to alpha-asarone.

The effect of alpha-asarone, a chemical with hypocholesterolemic properties extracted from Guatteria gaumeri, on SCE induction was studied both in human lymphocytes in vitro and in murine bone marrow cells in vivo. A slight but consistent increase in SCE was observed in both biological systems.