Augusto Langeloh

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.

Pharmacological investigations on Achyrocline satureioides (Lam.) DC., compositae

Achyrocline satureioides (Lam.) DC. inflorescences have been used as remedies in folk medicine for the treatment of a variety of human ailments, particularly those of the gastrointestinal tract. Different extracts of inflorescences have been tested for anti-inflammatory, analgesic, antispasmodic, constipating and sedative activities. The aqueous extracts (maceration and decoction) and ethanolic macerate exhibited an inhibition of the carrageenan-induced rat paw oedema at a dose range of 75-500 mg kg-1 i.p., and also showed analgesic effect with the acetic acid-induced writhing test in mice. The gastrointestinal propulsion of a charcoal suspension was not affected significantly by any extract, at a dose of 200 mg kg-1 p.o., in mice. The aqueous decoction increased pentobarbital-induced sleeping time, at doses of 200 and 500 mg kg-1 i.p. and p.o., in mice. The ethanolic macerate inhibited contractions induced by acetylcholine, histamine, noradrenaline and barium chloride in four different smooth muscle tissues. The antispasmodic and anti-inflammatory activities were reproduced with quercetin, luteolin and quercetin 3-methyl ether, flavonoids that have been isolated from this plant. A partial evaluation of the toxicity of the extracts was also performed. The pharmacological effects assayed are discussed in relation to the chemical constituents of this plant and its popular use in gastrointestinal disturbances, and inflammatory conditions could be related to the presence of the flavonoids.

Reproductive effects of endosulfan on male offspring of rats exposed during pregnancy and lactation

1 The reproductive effects of endosulfan on the male offspring of rats were examined. Dams were treated orally with 0, 1.5 or 3.0 mg endosulfan/kg from day 15 of pregnancy to postnatal day (PND) 21 of lactation. The male offspring rats were investigated at PND 65 or 140, corresponding to the pubertal and adulthood stage of development. 2 The dose of 3.0 mg endosulfan/kg induced a decrease in maternal body weight during pregnancy, but litter size and mean birth weight were not affected. Similarly, the age at testis descent and preputial separation was not affected on the male offspring. 3 The daily sperm production (6106) was permanently decreased in the highest dose group when investigated at puberty and at adulthood. At the lowest dose, however, the daily sperm production was significantly reduced only at puberty. 4 Histologically, the percentage of seminiferous tubules showing complete spermatogenesis was significantly decreased at puberty. This finding may explain the decrease in daily sperm production observed in the endosulfan-exposed male rats. 5 The results of this study show that low doses of endosulfan have no apparent effect on developmental landmarks or on the weight of reproductive and accessory sex organ. Daily sperm production was the most susceptible endpoint in the male offspring exposed to endosulfan during pregnancy and lactation. To further understand the reproductive effects of endosulfan on male rat offspring, additional reproductive and toxicokinetic studies should be carried out to determine the extent of endosulfan exposure in male rat offspring in utero and during lactation.

Analysis of the abortive and/or infertilizing activity of Stryphnodendron adstringens (Mart. Coville)

Stryphnodendron adstringens (barbatimao) e uma arvore natural dos Estados do Para ao Mato Grosso do Sul e Sao Paulo (Brasil). O objetivo deste estudo foi determinar a toxicidade dos extratos das vagens desta especie e verificar efeitos sobre a gestacao de ratas. As vagens foram coletadas na regiao de Cuiaba (MT, Brasil) e separadas em cascas e sementes. Foram feitos extratos brutos hidroalcoolicos (2:1), a frio e depois levados a secura (maximo 55°C). Ratas femeas virgens foram acasaladas e receberam extratos (0,5 ml/100 g de peso, 100 g/l) ou agua na mesma proporcao (controle) por gavagem do 1° ao 7° dia de gestacao. No 7° dia, foram feitas laparatomias para contagem do numero de implantes uterinos. As ratas foram sacrificadas no 21° dia de gestacao. Os extratos das sementes reduziram o peso do utero e o numero de fetos vivos em relacao ao grupo controle. A dose media letal (DL50) calculada para o extrato das sementes foi de 4.992,8 mg/kg. A DL50 do extrato das vagens foi maior que 5.000 mg/kg. Pode-se concluir que o extrato das sementes de S. adstringens interfere na gestacao de ratas, sendo que esta ingestao pode prejudicar animais herbivoros.

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.

Influência da administração de extratos de duas plantas calcinogênicas sobre a fertilidade de ratos

Investigou-se o efeito de extratos aquosos de Solanum malacoxylon (Sendter) Solanaceae (SM) (sin.: S. glaucophyllum) e Nierembergia veitchii (Hook) Solanaceae (NV), plantas calcinogenicas encontradas no Brasil, sobre a reproducao de ratos e sobre suas progenies. No experimento 1, ratos e ratas Wistar, em numero variavel conforme o grupo, receberam por via oral, durante os 40 dias anteriores ao acasalamento, extrato aquoso de ambas as plantas em dosagem equivalente a administracao diaria de 10,9g´kg-1 de planta seca. Os resultados foram comparados com os de um grupo tratado diariamente com vitamina D3 (3,0mg´kg-1) e com os de um grupo-controle (salina). No experimento 2, ratas prenhes receberam, por via oral, tres diferentes doses dos extratos de ambas as plantas (equivalente a administracao diaria de 5,4; 10,9 e 21,7g´kg-1 de planta seca), durante toda a gestacao. Os resultados foram comparados com tres grupos tratados com vitamina D3 (0,75; 2,25 e 3,75mg´kg-1) e um grupo-controle (salina). Quando administradas antes da gestacao, o ganho de peso das femeas e a fertilidade foram reduzidos nos grupos tratados com SM (11%) e vitamina D3 (11%). No grupo tratado com NV, a fertilidade tambem foi reduzida (25%), mas o desenvolvimento ponderal durante o tratamento nao foi afetado. Nos grupos tratados com SM e vitamina D3 anterior a gestacao, o numero de filhotes por ninhada foi reduzido, assim como o seu peso ao nascer. Caracteristicas de desenvolvimento e desempenho fisico dos filhotes nao foram afetados em nenhum dos grupos. O tratamento das femeas com extrato aquoso de SM durante a gestacao causou reducao significativa e dose-dependente nas caracteristicas reprodutivas estudadas. O mesmo foi observado com as femeas tratadas com vitamina D3. Com o extrato aquoso de NV nao foram observadas reducoes nas taxas reprodutivas, quando as femeas foram tratadas durante a gestacao. Com as doses 10,9 e 21,7g´kg-1 de NV foram observadas anomalias morfologicas fetais (2,3 e 0,1%, respectivamente), tambem presentes nos filhotes de femeas tratadas com vitamina D3 (2,25mg´kg-1). A presenca de vitamina D3 e seus metabolitos nas plantas calcinogenicas provavelmente e responsavel pela infertilidade observada, nao somente devido a toxicidade sistemica, mas tambem devido aos seus efeitos especificos sobre o aparelho reprodutor.

Efeito de Hypericum caprifoliatum Cham. & Schltdl. (Guttiferae) sobre contrações em íleo isolado de cobaio induzidas por diferentes agonistas

In the last decade the genus Hypericum has achieved worldwide recognition due to the therapeutic value of H. perforatum as an antidepressant drug. Consequently this activity is the most investigated one. However, species native to Brazil have other folk uses such as for the treatment of digestive disorders, including cramps. In this study we evaluated the effect of a purified cyclohexane extract (chlorophyll and waxes free) (1,3,10 and 30 mg/mL) of H. caprifoliatum, a specie native to South Brazil, on isolated guinea pig ileum contractions induced by different mediators: serotonin, histamine, acetylcholine and potassium chloride (10-7 - 10-4 M). At 30 mg/mL all contractile responses were abolished. At 10 mg/mL only serotonin responses were altered: the extract reduced the maximal effect in 50%, which represents a non-competitive antagonism. At 1 and 3 mg/mL the extract was unable to modify all mediators response. These results point to native species of Hypericum as an interesting perspective in searching new molecules active on gastrointestinal motility.

A prescrição racional em medicina veterinária e os nomes dos fármacos dos medicamentos alopáticos

Drugs can be designed by their chemical name, by their generic (or non proprietary) names and by the commercial (or proprietary) name. Drugs can be marketed by more than one company and can have several proprietary or trademark names. In Brazil pharmaceutical companies which produce veterinary drugs use different chemical or generic names to designe the active drug of medicines. This clearly create difficulties for veterinarians inducing errors andmisuses. Medicines for human use on the other hand have a official generic (non-proprietary) name known as Denominacoes Comuns Brasileiras (Brazilian Common Denomination) which were adopted in accordance with the World Health Organization recomendations. It is stressed that Brazilian Oficial non-proprietary names should also be adopted by manufacturers of veterinary drugs. This would either help to eliminate the necessity for memorizing multiple chemical and generic drug names as been as reduce the possibility of misunderstanding and errors. If veterinary medicines would be marketed in various South-American countries, as a result from the Mercosul comercial agreement, the existence of many names for the same drug can result in an even more conjuse situation. This article deals with this problem and calls for attention for the uniformity of drug nomes.