Prenatal effects of natural calcium supplement on Wistar rats during organogenesis period of pregnancy.

The potential of oral exposure to calcium and magnesium citrate, a natural product obtained from dolomite, to initiate teratogenesis was analyzed in Wistar rats. Animals received calcium and magnesium citrate oral doses of 250, 500 and 1000 mg/kg during the period of gestation from day 6 to 17 post conception. Maternal, embryo and fetal toxicity was evaluated. Calcium and magnesium citrate exposure did not produce maternal toxicity assessed by clinical observations, body weight gain, food intake, hematology, biochemical parameters and necropsy finding. Signs of embryo-fetal toxicity were not observed. Skeletal and visceral malformations were seen occasionally in all drug-treated and control groups. Skeletal and visceral variations were similar in control and drug-treated groups except for incomplete ossification rib. These finding was spontaneous and unrelated to the drug. In conclusion, in this study we found that the oral exposure to rats of up to 1000 mg/kg of calcium and magnesium citrate during organogenesis did not induce significant maternal and embryo-fetal toxicity. The experimentally derived NOAEL for developmental toxicity was 1000 mg/kg.

Short-term intra-nasal erythropoietin administration with low sialic acid content is without toxicity or erythropoietic effects.

The objective of this investigation was to assess the toxicological potential of nasal formulation of erythropoietin with low sialic acid content (Neuro EPO) after 28 days of intra-nasal dosing in rats besides to evaluate the immunogenicity and erythropoietic effect of the test substance. Healthy Wistar rats of both sexes were used for 28 days subacute toxicity and immunogenicity assays. Doses evaluated were 3450, 4830 and 6900 UI/kg/day. The toxicological endpoints examined included animal body weight, food consumption, hematological and biochemical patterns, antibodies determination, selected tissue weights and histopathological examination. Reversibility of toxic effects was evaluated at high dose 14 days after treatment period. Female B6D2F1 mice were used for evaluated erythropoietic effect of the nasal formulation. Hematological endpoints were examined every week during 28 days of intra-nasal dosing of 6900 UI/kg/day. Variations of hematological patterns were not observed after 28 days of intranasal dosing. A slight increase in glucose level of treated animals within the normal range was observed. This effect was not dose related and was reversible. Antibody formation was not observed in any of the test doses. Histopathological examination of organs and tissues did not reveal treatment induced changes. The administration of Neuro EPO in normocythaemic mice did not produce erythropoietic effect. These results suggest that Neuro EPO could be used as a neuroprotective agent, without significant systemic haematological side effects.

Absence of hematological side effects in acute and subacute nasal dosing of erythropoietin with a low content of sialic acid.

The use of human recombinant erythropoietin (EPO) as a neuroprotective agent is limited due to its hematological side effects. An erythropoietin along with a low content of sialic acid (rhEPOb), similar to that produced in the brain during hypoxia, may be used as a neuroprotective agent without risk of thrombotic events. The objective of this investigation was to assess the toxicological potential of a nasal formulation with rhEPOb in acute, subacute and nasal irritation assays in rats. Healthy Wistar rats (Cenp:Wistar) were used for the assays. In an irritation test, animals received 15 µl of rhEPOb into the right nostril. Rats were sacrificed after 24 h and slides of the nasal mucosa tissues were examined. Control and treated groups showed signs of a minimal irritation consisting of week edema and vascular congestion in all animals. In the acute toxicity test, the dose of 47,143 UI/kg was administered by nasal route. Hematological patterns, body weight, relative organ weight, and organ integrity were not affected by single dosing with rhEPOb. In the subacute toxicity test, Wistar rats of both sexes received 6,600 UI/kg/day for 14 days. The toxicological endpoints examined included animal body weight, food consumption, hematological and biochemical patterns, selected tissue weights, and histopathological examinations. An increase of lymphocytes was observed in males that was considered to reflect an immune response to treatment. Histopathological examination of organs and tissues did not reveal treatment-induced changes. The administration of rhEPOb at daily doses of 6,600 UI/kg during 14 days did not produce hematological side effects. These results suggest that rhEPOb could offer the same neuroprotection as EPO, without hematological side effects.

Toxicidad aguda oral y ensayos de irritación de extractos acuoso e hidroalcohólico de Momordica charantia L / Acute oral toxicity and irritation tests in aqueous hydroalcoholic extracts from Momordica charantia L

Fundamentación: los extractos de Momordica charantia L. poseen potencial terapéutico avalado científicamente que posibilita el empleo de esta planta en diversas enfermedades, sobre todo en la diabetes, por lo que caracterizar su potencial tóxico es de gran importancia para avalar el empleo de esta planta como agente terapéutico. Objetivos: realizar los estudios de toxicidad aguda oral e irritación ocular y dérmica a extractos acuoso e hidroalcohólico de M. charantia, con la finalidad de caracterizar su potencial toxicológico agudo. Métodos: el ensayo de toxicidad aguda oral se llevó a cabo en ratas Wistar hembras mediante el método de las clases tóxicas agudas, con la dosis máxima de 2 000 mg/kg. Los ensayos de irritación dérmica y ocular se llevaron a cabo en conejos Nueva Zelanda siguiendo los métodos descritos en las normas OECD 404 y 405. Resultados: la evaluación del extracto hidroalcohólico de M. charantia en el ensayo de toxicidad aguda mostró signos tóxicos por causa de la presencia de etanol en el extracto y una ligera disminución del peso corporal que no fue significativa. La administración del extracto acuoso no provocó signos tóxicos ni mortalidad. Ambos extractos se clasificaron en categoría 5 para ubicarse en el rango de toxicidad de una DL50> 2 000 mg/kg. En el ensayo de irritación dérmica y ocular se clasificaron los extractos como no irritantes. Conclusiones: los extractos evaluados mostraron un bajo potencial tóxico agudo tanto por vía oral como tópica.

Rationale: Momordica charantia L. extracts have scientifically-endorsed therapeutical potentialities that make the use of this plant possible in several diseases, mainly for diabetes, so characterizing its toxic potential is of great significance to support this plant as a therapeutical agent. Objectives: to conduct acute oral toxicity and ocular and dermal irritation studies on aqueous hydroalcoholic extracts from M. charantia, with the aim of characterizing its acute toxicological potential. Methods: Acute oral toxicity test was applied to female Wistar rats through acute toxic class method, with maximum dose of 2000 mg/kg. Ocular/dermal irritation tests were made in New Zealand rabbits, following the described methods in OECD standards 404 and 405. Results: the evaluation of M. charantia hydroalcoholic extract in the acute toxicity test showed toxic signs due to ethanol in the extract and a minimum bodyweight reduction that was not significant. The administration of water extract elicited neither toxic signs nor mortality. Both extracts were classified into category 5 within the range of toxicity of DL50> 2 000 mg/kg. The dermal/ocular irritation test indicated that the studied extracts were not irritating. Conclusions: The evaluated extracts showed low acute toxic potential for both oral and topical administration.

Toxicidad aguda oral y ensayos de irritación de extractos acuoso e hidroalcohólico de Momordica charantia L / Acute oral toxicity and irritation tests in aqueous hydroalcoholic extracts from Momordica charantia L

Fundamentación: los extractos de Momordica charantia L. poseen potencial terapéutico avalado científicamente que posibilita el empleo de esta planta en diversas enfermedades, sobre todo en la diabetes, por lo que caracterizar su potencial tóxico es de gran importancia para avalar el empleo de esta planta como agente terapéutico. Objetivos: realizar los estudios de toxicidad aguda oral e irritación ocular y dérmica a extractos acuoso e hidroalcohólico de M. charantia, con la finalidad de caracterizar su potencial toxicológico agudo. Métodos: el ensayo de toxicidad aguda oral se llevó a cabo en ratas Wistar hembras mediante el método de las clases tóxicas agudas, con la dosis máxima de 2 000 mg/kg. Los ensayos de irritación dérmica y ocular se llevaron a cabo en conejos Nueva Zelanda siguiendo los métodos descritos en las normas OECD 404 y 405. Resultados: la evaluación del extracto hidroalcohólico de M. charantia en el ensayo de toxicidad aguda mostró signos tóxicos por causa de la presencia de etanol en el extracto y una ligera disminución del peso corporal que no fue significativa. La administración del extracto acuoso no provocó signos tóxicos ni mortalidad. Ambos extractos se clasificaron en categoría 5 para ubicarse en el rango de toxicidad de una DL50> 2 000 mg/kg. En el ensayo de irritación dérmica y ocular se clasificaron los extractos como no irritantes. Conclusiones: los extractos evaluados mostraron un bajo potencial tóxico agudo tanto por vía oral como tópica(AU)

Rationale: Momordica charantia L. extracts have scientifically-endorsed therapeutical potentialities that make the use of this plant possible in several diseases, mainly for diabetes, so characterizing its toxic potential is of great significance to support this plant as a therapeutical agent. Objectives: to conduct acute oral toxicity and ocular and dermal irritation studies on aqueous hydroalcoholic extracts from M. charantia, with the aim of characterizing its acute toxicological potential. Methods: Acute oral toxicity test was applied to female Wistar rats through acute toxic class method, with maximum dose of 2000 mg/kg. Ocular/dermal irritation tests were made in New Zealand rabbits, following the described methods in OECD standards 404 and 405. Results: the evaluation of M. charantia hydroalcoholic extract in the acute toxicity test showed toxic signs due to ethanol in the extract and a minimum bodyweight reduction that was not significant. The administration of water extract elicited neither toxic signs nor mortality. Both extracts were classified into category 5 within the range of toxicity of DL50> 2 000 mg/kg. The dermal/ocular irritation test indicated that the studied extracts were not irritating. Conclusions: The evaluated extracts showed low acute toxic potential for both oral and topical administration(AU)

Effect of dolomite oral exposure in Wistar rats during organogenesis period of pregnancy.

The potential of oral exposure to dolomite, a natural product that contains calcium and magnesium, to initiate teratogenesis was analyzed in Wistar rats. Animals received dolomite oral dosages of 500 and 1500mg/kg during the period of gestation from day 6-15 post conceptionem (p.c.). Maternal, embryo and fetal toxicity were evaluated. Dolomite exposure did not produce maternal toxicity assessed by clinical observations, body weight gain, hematology parameters and relative organs weight. Signs of embryo-fetal toxicity were not observed. Skeletal malformations and visceral variations were similar in control and dolomite-treated groups. On the other hand, slight increase was observed in fetal body weight in the dolomite-treated group. Treatment with dolomite resulted in significantly decreased incidences of unossified xiphisternum, incomplete ossification of xiphisternum and sternebrae. These effects could be caused by a beneficial influence of calcium and magnesium salts present in dolomite on ossification process. In conclusion, in this study we found that the oral exposure to rats of up to 1500mg/kg of dolomite during organogenesis did not induce significant maternal and embryo-fetal toxicity.