Efeitos tóxicos de compostos de vanádio sobre os parâmetros biológicos de embriões e adultos de zebrafish (Danio rerio) / Toxic effects of vanadium compounds on biological parameters of embryos and adults of zebrafish (Danio rerio)

Foram avaliados os efeitos tóxicos do metavanadato de sódio (MV), pentóxido de vanádio (PV) e sulfato de oxovanádio (SV), potenciais fármacos antidiabéticos, em embriões e adultos de zebrafish (Danio rerio). Os embriões foram expostos a concentrações de 10-1000µg/mL para avaliação da CL50 96h e seus efeitos teratogênicos. Os adultos foram expostos a 10 e 20µg/mL dos mesmos compostos para se avaliarem alterações comportamentais relacionadas à exposição química e à mortalidade. A CL50 96h foi de 22,48, 53,62 e 74,14µg/mL para MV, SV e PV, respectivamente. Houve 100% de mortalidade nas concentrações de 400-1000µg/mL dos três compostos. Os efeitos teratogênicos mais observados (P<0,05) nos embriões foram edemas de pericárdio e saco vitelínico. Foram constatados, nos animais adultos expostos aos compostos de vanádio, maior batimento opercular e congestão nos arcos branquiais. A exibição dos comportamentos Flutuar e Descansar nos adultos expostos foi significativa (P<0,05), como também a exibição do comportamento Respiração Aérea. Pode-se concluir que a exposição química aos compostos de vanádio causou efeitos tóxicos em embriões e adultos de zebrafish com alta mortalidade. Diante disso, o seu uso como potencial fármaco antidiabético deve ser mais bem estudado em razão do efeito tóxico dessas substâncias.(AU)

The toxic effects of sodium metavanadate (MV), vanadium pentoxide (PV) and oxovanadium sulfate (SV), potential antidiabetic drug, on embryos and adults of zebrafish (Danio rerio) were evaluated. Embryos were exposed to concentrations of 10-1000µg/mL for evaluation of 96-h LC50 and their teratogenic effects. Adults were exposed to 10 and 20µg/mL of the same compounds to evaluate behavioral changes related to chemical exposure and mortality. The 96-h LC50 were 22.48, 53.62, and 74.14µg/mL for MV, SV, and PV, respectively. Mortality of 100% was observed at the concentrations of 400-1000µg/mL of the three compounds. The teratogenic effects most observed (P<0.05) were pericardial and yolk sac edemas. Adult animals exposed to the vanadium compounds had higher opercular beats and congestion in the gill arches. The exhibition of behaviors Floating and Resting in the exposed adults was significant (P<0.05), as well as the Air breathing behavior. Chemical exposure to vanadium compounds caused toxic effects in embryos and adults of zebrafish with high mortality. In conclusion, its use as a potential antidiabetic drug should be better studied due to the toxic effect.(AU)

Facts about Magnesium Sulfate: Time to Revise the Safety Concern in Obstetric Use.

Magnesium sulfate (MgSO4) is the agent most commonly used for treatment of eclampsia and prevention of eclampsia in patients with severe pre-eclampsia. Another commonly practiced offlabel use of this drug is in preventing preterm labor in pregnant women where the duration of the treatment might be more than one week. It is usually given either by intramuscular or intravenous route. After administration, about 40% of plasma magnesium is bound with protein. The unbound magnesium ion diffuses into the extravascular extracellular space and then diffuses into bone. It also crosses the placenta and fetal membranes and then diffuses into the fetus and amniotic fluid. Magnesium is almost exclusively excreted in the urine; 90% of the dose is excreted during the first 24 hours after an intravenous infusion of MgSO4. The clinical effect and toxicity of MgSO4 can be linked to its concentration in plasma. A concentration of 1.8–3.0 mmol/L has been suggested for treatment of eclampsia. The actual magnesium dose and concentration needed for prophylaxis have never been estimated. Maternal toxicity is rare when MgSO4 is carefully administered and monitored. Deep tendon reflexes, respiratory rate, urine output and serum concentrations are the most common variables for monitoring the toxic effect. Currently the United States (US) Food and Drug Administration (FDA) is advising health care professionals against using MgSO4 injection for more than 5–7 days to stop preterm labor in pregnant women (off-label use). Administration of MgSO4 injection to pregnant women for more than 5–7 days may lead to low calcium levels and bone problems in the fetus, including osteopenia and fractures. The harmful effect in the fetus with the shortest duration is not established. In light of this new safety information, the drug label for MgSO4 injection, USP 50% has also been changed, including changing the pregnancy category to D from A and denoting the effect as “New teratogenic effects”. Similarly, the manufacturers of other MgSO4 injection products have made similar changes to their drug labels. In this review, the currently available knowledge of the pharmacokinetics of MgSO4 and its clinical usage for women with pre-eclampsia and eclampsia, its off-label use and safety concern regarding the warning announced by the FDA will be outlined.

Manifestaciones cutáneas como parámetro de teratogenicidad en la intoxicación con metales pesados / Cutaneous signs as parameter in teratogenicity by heavy metal intoxication

Se estudiaron los efectos teratogénicos de metales pesados (acetatos de Cd2+ y Pb2+ y sulfato de Cu2+), en embriones de pollo en desarrollo, después de la administración de una monodosis del metal. Los huevos embrionados fueron inyectados en la yema en el día 12 de incubación. Las concentraciones de los iones fueron (nmoles/g huevo): Cd2+: Dosis 1 (D1): 0,16 y Dosis 2 (D2): 0,32; Pb2+: D1: 8,0 y D2: 16,0 y Cu2+: D1: 1,7 y D2: 3,3. Los resultados se evaluaron después de continuar la incubación in ovo durante 12 y 60 hs Cu2+ y Pb2+ no aumentaron la mortalidad de los embriones, en cambio, la presencia de Cd2+ produjo entre 30 y 86 % de mortalidad de los embriones, con efectos dosis y tiempo dependientes. Los embriones intoxicados con la D2 de Cd2+ durante 60 hs fueron los únicos ejemplares que presentaron disminución en su peso promedio, respecto de los ejemplares de control. La administración de Cd2+ causó efectos teratogénicos más severos que los tratamientos con Cu2+ y Pb2+. Se puede concluir que los metales pesados son embriotóxicos e inducen teratogenia en embriones de pollo en desarrollo. Se sugiere que los mejores parámetros para evaluar la teratogenicidad producida por la intoxicación Cd2+, Cu2+ y Pb2+ son los derrames cutáneos y hepáticos.

Teratogenic effects of heavy metals (Cd2+- and Pb2+- acetates and Cu2+- suphate) were studied on chick embryos, after the administration as a single dose. Test materials were injected into the yolk on day 12 of incubation. Tested concentrations were (nmole/g egg): Cd2+ Dose 1 (D1): 0.16 and Dose 2 (D2): 0.32; Pb2+: D1: 8.0 and D2: 16.0 and Cu2+: D1: 1.7 and D2: 3.3. Evaluations were performed after in ovo incubation for 12 and 60 hours. Embryonic mortality did not increase at the two dose levels of Cu2+ and Pb2+, while Cd2+ caused 30 and 86% of mortality, showing dose and time responses. Eggs treated with D2 of Cd2+ for 60 hs, significantly decreased the average of body mass embryo, when compared to the control group. Cd2+ administration was responsible for the most severe teratogenic signs compared to Cu2+ and Pb2+ treatments. It can be concluded that heavy metals are embryotoxic and teratogenics. We suggest that cutaneous and liver hemorrhages are the best signs to evaluate teratogenicity induced by Cd2+, Cu2+ and Pb2+.

Application of the Teratogenic Effects of Embryo Development in Zebrafish to the Determination of Toxicity of Environmental Pollutants / 环境与健康杂志

The embryo development technique in Zebrafish, Brachydanio rerio, is a toxicity testing method making use of the high sensitivity of fish embryo development in early stage to study and evaluate the specific effecting mechanism, the most sensitive effecting time, embryo toxicity and teratogenicity of chemicals through observing the development process of zebrafish embryo after chemical exposure to fertilized ova. This technique has been widely used to test toxicity of chemicals with the advantages of low cost, high sensitivity, simple to operate and simultaneous to detect multi-endpoints. The main methodology, technical characteristics and the status of world-wide application of this technique are reviewed in this paper. Based on the urgent environmental problems in China, the prospects to use this method for monitoring toxicity of mixed pollutants in wastewater are put forward.

A Teratological Study of Sprague-Dawley Rats with 3 (or 8)-(l-Methoxyethyl)-8 (or 3)-hydroxyethyl-deuteroporphyrin / 第二军医大学学报

The potential embryotoxicity, developmental toxicity and teratogenic effects of (3 or 8)-(l-methoxyethyl)-8 (or3)-hydroxyethyl-deuteroporphyrin (PsD-044) were investigated in Sprague-Dawley rats with the conventional teratological method in vivo. According to the recommending clinical dosage, PsD-044 was administered intravenously at 20, 10 and 5mg/kg, as compared to the negative control with saline and the positive control with sodium pentachlorophenolate, respectively on the 10th day of the gestation. Eighty-one pregnant rats and 803 fetuses were examined. The results suggest that the maternal toxicity, embryotoxicity and teratogenic effects of PsD-044 were not found, however, the malformation induced by known teratogen was as high as 14.1%.