Vitamin C administration attenuated artemether induced hepatic injury in rats / La aAdministración de vitamina C atenúa la lesión hepática inducida por artemeter en ratas

This research was designed to investigate the potential protective effect of vitamin C supplementation against hepatocyte ultrastructural alterations induced by artemether (antimalarial drug) administration. Twenty-four adult male albino rats were used in this study and were divided into four groups (n=6). Group I served as a control and rats in group II administrated artemether (4 mg/kg B.W) orally for three consecutive days. Group III administered artemether plus a low dose of vitamin C (2.86 mg/kg/l water) while group IV received artemether plusa high dose of vitamin C (8.56 mg/kg). At the end of the experimental period (14 days), the harvested liver tissues were examined by transmission electron microscopy (TEM), and blood samples were assayed for biomarkers of liver injury and oxidative stress. Artemether significantly (p<0.05) augmented biomarkers of liver injury such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and oxidative stress such as superoxide dismutase (SOD), Glutathione Peroxidase (GPX), and caused degeneration and damage of the rough endoplasmic reticulum and disrupted mitochondria. The blood sinusoids were also damaged with distortion of their canaliculi. Administration of vitamin C showed improvement of liver biomarkers, and liver parenchyma, especially in a high dose of vitamin C.We concludes that vitamin C is a partial protective agent against artemether-induced liver injury.

Esta investigación fue diseñada para investigar el posible efecto protector de la vitamina C contra las alteraciones ultraestructurales de los hepatocitos, inducidas por la administración de arteméter (medicamento antipalúdico). En el estudio se utilizaron 24 ratas albinas macho adultas y se dividieron en cuatro grupos (n = 6). El grupo I fue designado como control y las ratas en el grupo II se adminstró Arteméter (4 mg / kg de peso corporal) por vía oral durante tres días consecutivos. En el grupo III se administró arteméter, además de una dosis baja de vitamina C (2,86 mg / kg / l de agua) mientras que el grupo IV recibió arteméter más una dosis alta de vitamina C (8,56 mg / kg). Al final del período experimental (14 días), los tejidos hepáticos recolectados se examinaron por microscopía electrónica de transmisión (MET), y las muestras de sangre se analizaron en busca de biomarcadores de daño hepático y estrés oxidativo. El arteméter aumentó significativamente (p <0,05) los biomarcadores de daño hepático como alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y estrés oxidativo como superóxido dismutasa (SOD), glutatión peroxidasa (GPX) y causó degeneración y daño de la retículo endoplásmico rugoso y mitocondrias alteradas. Los sinusoides sanguíneos también fueron dañados con la distorsión de sus canalículos. La administración de vitamina C mostró una mejoría de los biomarcadores hepáticos y el parénquima hepático, especialmente en una dosis alta de vitamina C. Concluimos que la vitamina C es un agente protector parcial contra la lesión hepática inducida por arteméter.

Concentration of free vascular endothelial growth factor and its soluble receptor, sFlt-1 in the maternal and fetal circulations of normal term pregnancies at high and low altitudes.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is regulated by hypoxia that is essential for placental development. It is antagonized by a soluble form of its receptor (sFlt-1). The purpose of this study was to measure these factors in the maternal and the cord bloods, at low and high altitude. METHODS: Samples were collected from full term births normal pregnant women. Free (unbound) VEGF and sFlt-1 levels were measured in plasma samples from cord and maternal blood for each subject by enzyme-linked immunosorbent assay (ELISA) using commercially available kits from R&D systems, UK (Cat # DVE00 and Cat # SVR100B, respectively). RESULTS: At high altitude, the average maternal free VEGF in pg/ml was significantly (p < 0.001) lower than that of the cord level (71.30 ± 282.14 and 431.35 ± 424.31, respectively). On the other hand, the average maternal sFlt-1 was significantly (p < 0.001) higher than that of the cord level (8205.41 ± 6244.72 and 1811.74 + 3469.30, respectively). At low altitude, the average maternal free VEGF was significantly lower than that of the cord level (0.47 ± 0.89 and 483.44 ± 457.31, respectively, p < 0.001). On the other hand, the average maternal sFlt-1 was significantly higher than that of the cord level (9267.82 ± 6345.68 and 958.66 ± 1359.92, respectively, p < 0.001). There were no significant differences by altitude. CONCLUSION: Secretion of sFlt-1 appears to be polarized, in that concentrations are higher in the maternal compartment than on the fetal side at both high and low altitudes. This may be a normal physiological phenomenon to permit angiogenesis in the placenta and fetus while protecting the mother. Chronic exposure to hypobaric hypoxia at high altitude does not affect these distributions.

Concentrations of free vascular endothelial growth factor in the maternal and foetal circulations during pregnancy: a cross-sectional study.

OBJECTIVE: To investigate the concentrations of free plasma vascular endothelial growth factor (VEGF) in the maternal and foetal circulations of normal term pregnancies. METHODS: Free plasma VEGF was measured from plasma of umbilical cord and maternal blood by ELISA for each of 20 normal pregnancies delivering at term at an altitude of 3100 m. Spearman's correlation coefficient was used to test for correlation between values and clinical maternal and neonatal data. Student's 't' test was used to test for differences between samples from male and female neonates. RESULTS: Free plasma VEGF was undetectable from maternal samples, but it was detectable in the cord blood (mean, 560.3775 pg/ml, median, 145.84 pg/ml, range, 22.56-2653.5). No differences were found between neonates sex, and no correlation was found with clinical maternal and neonatal data. CONCLUSION: Circulating VEGF is usually bound to the soluble form of its receptor 1 (sFlt-1). High levels of sFlt-1 are secreted by the syncytiotrophoblast during pregnancy, and so free plasma VEGF is undetectable in the maternal circulation. In contrast, our findings are the first to show free plasma VEGF in the umbilical circulation. We speculate that this free VEGF may promote angiogenesis in the foetus and placenta. Our data imply that sFlt-1 is not present in the cord blood, and that secretion by the syncytiotrophoblast is polarised to its apical surface. Further investigations are required to test this hypothesis.