Eliane Dallegrave

Pre-and postnatal toxicity of the commercial glyphosate formulation in Wistar rats

Glyphosate is the active ingredient and polyoxyethyleneamine is the surfactant present in the herbicide Roundup® formulation commercialized in Brazil. The aim of this study was to assess the reproductive effects of glyphosate-Roundup® on male and female offspring of Wistar rats exposed during pregnancy and lactation. Dams were treated orally with water or 50, 150 or 450xa0mg/kg glyphosate during pregnancy (21–23xa0days) and lactation (21xa0days). These doses do not correspond to human exposure levels. The results showed that glyphosate-Roundup® did not induce maternal toxicity but induced adverse reproductive effects on male offspring rats: a decrease in sperm number per epididymis tail and in daily sperm production during adulthood, an increase in the percentage of abnormal sperms and a dose-related decrease in the serum testosterone level at puberty, and signs of individual spermatid degeneration during both periods. There was only a vaginal canal-opening delay in the exposed female offspring. These findings suggest that in utero and lactational exposure to glyphosate-Roundup® may induce significant adverse effects on the reproductive system of male Wistar rats at puberty and during adulthood.

The teratogenic potential of the herbicide glyphosate-Roundup in Wistar rats

The aim of this study was to assess the teratogenicity of the herbicide glyphosate-Roundup (as commercialized in Brazil) to Wistar rats. Dams were treated orally with water or 500, 750 or 1000 mg/kg glyphosate from day 6 to 15 of pregnancy. Cesarean sections were performed on day 21 of pregnancy, and number of corpora lutea, implantation sites, living and dead fetuses, and resorptions were recorded. Weight and gender of the fetuses were determined, and fetuses were examined for external malformations and skeletal alterations. The organs of the dams were removed and weighed. Results showed a 50%, mortality rate for dams treated with 1000 mg/kg glyphosate. Skeletal alterations were observed in 15.4, 33.1, 42.0 and 57.3% of fetuses from the control, 500, 750 and 1000 mg/kg glyphosate groups, respectively. We may conclude that glyphosate-Roundup is toxic to the dams and induces developmental retardation of the fetal skeleton.

Pre and postnatal exposure to endosulfan in Wistar rats.

The possible reproductive adverse effects of the pesticide endosulfan on male offspring rats exposed in utero and during lactation were investigated. Dams were treated orally with 0, 0.5 or 1.5 mg of endosulfan/kg 21 days prior to mating, during the mating, pregnancy and lactation. Maternal and reproductive outcome data and male sexual development landmarks (testis descent and preputial separation) were assessed. Reproductive endpoints of the male offspring were examined at adulthood: sex organ weights, daily sperm production, spermatid number, sperm transit, sperm morphology and testosterone level. No signs of maternal toxicity were detected at the dose levels tested. Sexual development landmarks were also unaffected. Moreover, with the exception of a significant increase in the relative epididymis weight seen in the group treated with the lowest dose, we have not found any statistically significant adverse effect in the reproductive endpoints investigated at adulthood. The results of the present study indicate that pre and post-natal exposure to low doses of endosulfan (0.5 and 1.5 mg/kg) do not induce significant adverse effects in the reproductive system of male offspring Wistar rats at adulthood.

Phenantroline, lovastatin, and mebendazole do not inhibit oviposition in the murine experimental infection with Angiostrongylus costaricensis.

Abdominal angiostrongyliasis is a zoonotic infection produced by a metastrongylid intra-arterial nematode, Angiostrongylus costaricensis. Human accidental infection may result in abdominal lesions. The presence of the eggs in the tissues plays an essential role in morbidity of abdominal angiostrongyliasis. The objective of this study is to evaluate and compare the effects of lovastatin, phenanthrolin, and mebendazole on oviposition of A. costaricensis in a murine experimental model. Each group of 12 male Swiss mice (Mus musculus) was orally infected with 10 L3 of the “Santa Rosa” strain of A. costaricensis. Two control groups were established: (1) mice were infected and not treated; (2) noninfected and nontreated animals. The experimental groups received (1) lovastatin TL), at a daily dose of 250xa0mg/kg for 10 consecutive days 16xa0days after infection; (2) phenanthroline at a daily dose of 20xa0mg/kg for 5 consecutive days 21xa0days after infection; and (3) mebendazole at a daily dose of 5xa0mg/kg for 5 consecutive days 21xa0days after infection. There was no significant inhibition of oviposition for lovastatin- and mebendazole-treated animals, whereas phenanthroline was associated with the lowest averages of larviposition per postinfection day and significant reduction of mortality.

Chemical and anti-ulcer evaluation of Jodina rhombifolia (Hook. & Arn.) Reissek extracts

Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) is a medicinal plant popularly used as an anti-ulcer medicine. The plant native from Southern Brazil was chemically investigated and tested for its in vivo gastric anti-ulcer property by chloride acid/ethanol model. The chromatographic analysis of the hydroethanol extract of its leaves revealed the presence of C-glycosylflavonoids. From the n-butanol fraction of the hydroethanol extract of its aerial parts, vicenin-2 was isolated as the main component and identified by spectroscopic methods; and, a direct comparison with authentic samples was made. This fraction afforded three other C-glycosylflavonoids: vitexin, orientin and swertisin; all of them identified by direct comparison with authentic samples. We found that the oral administration of aqueous and hydroethanolic extracts led to a significant decrease in the ulcer index.

Efeitos da ivermectina (Ivomec® 1% injetável) administrada a ratas Wistar durante o período de organogênese

In order to evaluate the possible effect of ivermectin used on pregnant animals, Wistar rats were treated orally on sixth pregnancy day, with dosage of 20 and 60 times higher than therapeutic dosage used to treat scabiosis in dogs and cats. During all pregnant period, body weight, water and pellet food consuption of dams were determined. The dams were sacrificed at term for the evaluation of maternal and fetal parameters. The numbers of corporea lutea, post implantation loss and living and death fetuses were recorded. Also the organs of dams were removed, weighted and histopatologically examined. Fetuses were weighted, sexed, examined for external macroscopic malformations. Results showed absence of systemic and reproductive toxicity. It is concluded that ivermectin is no toxic to the dams and fetus, when administered in the beginning of organogenic period.

Study of acute toxicity and investigation of the presence of β-N-methylamino-L-alanine in the Gunnera manicata L. a species native to Southern Brazil

Gunnera (Gunneraceae) forma uma complexa associacao com a cianobacteria Nostoc puctiforme L. A simbiose Gunnera-Nostoc e a unica relatada envolvendo uma angiosperma e, em decorrencia desta, ocorre a formacao da neurotoxina β-N-metilamino-L-alanina (BMAA). No sul do Brasil, encontra-se a especie G. manicata L., da qual nao constam, na literatura cientifica, estudos fitoquimicos, farmacologicos e toxicologicos. Assim, o presente estudo avaliou a toxicidade aguda e a presenca da neurotoxina BMAA em extratos aquosos de G. manicata. O ensaio de toxicidade aguda foi realizado com extrato aquoso das raizes de G. manicata na concentracao de 2000 mg/kg, administrado em dose unica via oral em ratos Wistar. Letalidade foi observada diariamente durante 14 dias pos-tratamento. Apos a eutanasia, a massa relativa dos orgaos foi analisada por ANOVA de uma via e investigou-se a presenca de alteracoes macroscopicas. A analise do BMAA por CG/EM envolveu uma etapa preliminar de derivatizacao, ja a analise por ESI-EM/EM foi realizada por infusao direta. O presente estudo demonstrou a ausencia da neurotoxina nas amostras de G. manicata analisadas bem como a ausencia de toxicidade aguda no extrato aquoso das raizes. Esses dados demonstram alta margem de seguranca dos extratos testados.

A 28-day Sub-acute Genotoxic and Behavioural Assessment of Garcinielliptone FC

Garcinielliptone FC (GFC) is a polyisoprenylated benzophenone isolated from Platonia insignis Mart (Clusiaceae) with promising anticonvulsant properties. However, its safe use and other effects on the central nervous system require assessment. This study assessed the toxicological effects of GFC using the comet assay and the micronucleus test in mice treated for 28 days. A behavioural model was employed to detect possible injuries on the central nervous system. Mice treated with GFC (2, 10 and 20 mg/kg; i.p.) daily for 28 days were submitted to rotarod test, open‐field test and tail suspension test (TST). After the behaviour tasks, biological samples were assessed to evaluate genotoxic and mutagenic effects using the comet assay and the micronucleus test. Garcinielliptone FC did not impair the performance of the animals in the rotarod and open‐field tests, with no antidepressant‐like effect in TST. No genotoxic effects in blood and cerebral cortex were observable in the comet assay; however, there was a significant increase in index and frequency of damage in liver after treatment with GFC 20 mg/kg. Garcinielliptone FC did not increase micronucleus frequency in bone marrow. At the tested doses, GFC was not toxic to the CNS and did not induce genotoxic damage to blood or bone narrow cells. DNA damage to liver tissue was caused only by the highest dose, although no mutagenic potential was observed.

SUSCEPTIBILITY AND MORBIDITY BETWEEN MALE AND FEMALE SWISS MICE INFECTED WITH Angiostrongylus costaricensis

The gender of vertebrate hosts may affect the outcome of parasitic infections. An experimental murine infection with Angiostrongylus costaricensis was followed with determinations of body weight, fecal larval elimination, number and length of adult worms, number of macroscopic intestinal lesions, and mortality. Groups of male and female Swiss mice were infected with 10 3(rd)-stage A. costaricensis larvae per animal. The results indicate there are no significant differences related to gender of the host, except for higher length of worms developed in male mice.