Gestational exposure to silymarin increases susceptibility of BALB/C mice fetuses to apoptosis

Background: silymarin is a flavonolignan that has been the subject of research to evaluate the beneficial properties for decades. Silymarin has been known for its potent cytoprotective, hepatoprotective and antioxidant activities. The goal of the present study was to gain a deeper understanding of possible molecular mechanisms of apoptosis of the injuries induced by silymarin on BALB/c mice fetuses

Methods: the present experimental study was carried out in virgin female BALB/c mice. The animals were divided randomly into 4 groups. Three test groups were injected intraperitoneally with silymarin at doses of 50, 100 and 200mg/kg/day during gestational days 6-15. The control group received the solvent by the same route at equivalent volume. Western blot analysis was conducted to determine the levels of caspase-3 and caspase-8 in fetal heart, kidney, lungs and brain tissue

Results: the results of this study showed that silymarin administration during organogenesis at doses of 50, 100 and 200 mg/kg can significantly increase the protein levels of caspase-3 and 8 in heart, kidneys and brain tissues of mice fetuses compared with control group [p<0.001]. Silymarin exposure could not change the level of apoptotic markers in fetal lung tissue

Conclusion: according to the results, programmed cell death, especially via the intrinsic pathway, plays a pivotal role in the pathogenesis of silymarin-induced malformations in some tissue including heart, kidneys and brain. More studies are needed to determine other molecular mechanisms underlying silymarin- induced embryo toxicity

Effects of omega-3 administration on homocysteine serum concentration in renal transplant recipient

It has been shown that serum total homocysteine [HC] is a risk factor for vascular disease which characterizes endothelial damage in the general and in the End-Stage Renal Disease [ESRD] population as well. Whether n-3 polyunsaturated fatty acids decrease homocysteine [Hcy] level has been a subject of controversy. Renal transplant patients were randomized in 2 groups and received 6 months of dietary supplementation with 6 g/day of Fish oil or placebo. Homocysteine level and total cholesterol level were measured. In 40 renal transplant recipients, increase in homocysteine level was greater after Fish oil administration but not significantly, total cholesterol was decreased significantly. Based on these data omega3 fatty acids supplementation doesn't decrease serum homocysteine in renal transplant recipients but decreases total cholesterol level.

Effects of erythropoietin on electrocardiogram changes in carbon monoxide poisoning: an experimental study in rats

The aim of this study was to define the electrocardiogram [ECG] changes following the moderate to severe CO intoxication in rats, and also evaluating the effect of erythropoietin [EPO] on observed cardiac disturbances. The growing literature on erythropoietin effect on cardiac ischemia led us to question its effect on cardiotoxicity due to the carbon monoxide poisoning. Wistar rats were exposed to three different concentrations of CO [250 PPM, 1000 PPM or 3000 PPM]. EPO was administrated [5000 IU/Kg, intraperitoneal injection] at the end of CO exposure and then the animals were re-oxygenated with ambient air. Subsequently ECG recording, heart rate and carboxyhemoglobin values were evaluated. ECG changes following the CO intoxication included ST segment elevation and depression, T wave inversion and first-degree AV block. Ischemic ECG changes reduced significantly in EPO-treated animals. In the present study, for the first time, EPO was investigated for the management of cardiac complications due to the CO poisoning. Our results showed that EPO could inhibit ischemic changes of ECG after the CO poisoning

Correlation between heat-shock protein 27 serum concentration and common carotid intima-media thickness in hemodialysis patients

Cardiovascular disease is a major factor in the deterioration of the health and the death of hemodialysis patients. Previous studies have mainly shown a decreased level of heat shock protein 27 [HSP27] in patients with cardiovascular disease. We conducted this study to investigate whether HSP27 correlates with common carotid intima-media thickness [CCIMT] and if it has a potential to be a biomarker for cardiovascular disease. In this cross-sectional study, the correlation between HSP27 serum concentration and CCIMT was investigated in 42 hemodialysis patients. An enzyme-linked immunosorbent assay method was used to measure HSP27 level in the plasma of the patients, and a high-resolution B-mode ultrasonography was applied to measure CCIMT. There was an inverse significant correlation between serum concentration of HSP27 and CCIMT only in patients that had hypertension as their only cardiovascular risk factor [r = 0.61, P = .02]. According to our results and the fact that HSP27 has been shown to be expressed in atherosclerotic plaques of both experimental animals and humans, we suggest that circulatory HSP27 concentration has a potential of being used as a marker for cardiovascular events

Preventive effect of vitamin B6 on developmental toxicity of carbamazepine in mice

Carbamazepine [CBZ] is an antiepileptic drug that is used widely for the treatment of epileptic seizures. Neural tube defects [NTDs], growth retardation, and nail hypoplasia are the most common features of teratogenic effects of this drug. The purpose of this study was to examine the effect of vitamin B6 on the developmental toxicity of CBZ on mice. Sixty BALB/c pregnant mice were divided into four experimental and two control groups. Two experimental groups received daily intraperitoneal [IP] of 30 mg/kg [I] or 60 mg/kg [II] of CBZ on gestational days [GD] 6 to 15. Two other experimental groups received daily IP injection of 30 mg/kg [III] or 60 mg/kg [IV] of CBZ with 10 mg/kg/day vitamin B6 by gavage 10 days prior to gestation and on GD 6 to 15. Two control groups received normal saline or Tween 20. Dams underwent Cesarean section on GD 18 and embryos were harvested. External/ macroscopic observation of fetuses was done by stereomicroscope and external examination for malformations was recorded. Data analyzed by ANOVA and X[2] test using SPSS software. The mean weight and crown-rump of the fetuses in both CBZ-treated experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, eye malformations, NTDs, vertebral deformity, brachydactyly and growth retardation. Vitamin B6 treatment significantly reduced various CBZ-induced malformations. This study showed that vitamin B6 has a preventive effect on the developmental toxicity of CBZ in mice that can be pursued further for clinical research

Teratogenic effects of gabapentin on the skeletal system of balb/C mice fetuses

To evaluate the effects of gabapentin [GBP] administration on mice fetuses. This study was carried out in Birjand University of Medical Sciences during 2008. Thirty Balb/c pregnant mice were divided randomly into 3 groups: 2 experimental groups that received 25 mg/kg [I] and 50 mg/kg [II] of GBP intraperitoneally for the first 15 days of pregnancy, and a control group that received normal saline. External observations of day 18 fetuses and skeleton double staining were performed. Both experimental groups showed similar disorders that can be categorized as the following: 1] decrease of fetal body weight and increase of fetal resorption, 2] macroscopic malformations, and 3] skeletal malformations. Fetal body weights were significantly lower, and fetus resorptions were significantly higher in both treated groups compared to the control group. Macroscopic malformations included exencephaly, limbs defects, brachygnathia, vertebral column deformity, and fetuses with severe retarded growth. Skeletal malformations included delayed ossification, scoliosis, calvaria deformity, and mandibular hypoplasia. This study revealed that GBP can induce previously unreported severe malformations if it is used continuously during the implantation, neurulation, and organogenesis stages of pregnancy. Therefore, it is suggested that great caution should be exercised in using GBP during the early stages of pregnancy until further studies are performed to better understand these effects

Eye malformations induced by carbamazepine in mice

Neural tube defects, growth retardation and nail hypoplasia are most common features of teratogenic effects of carbamazepine. This study was done to determine the effects of carbomazepine on eye development in Mice fetuses. In this experimental study 40 BALB/c pregnant Mice were divided into four groups. Experimental groups I and II received 15 mg/kg daily 6-15 GD [gestational days] and 30 mg/kg daily 6-15 GD intraperitoneal of carbamazepine, respectively. All drugs recolved in Tween20. Two control groups received normal saline or Tween 20. Dams were dissected on GD18 and embryos were collected. After observation of eye malformation in fetuses, we employed routine histological processes to stain the samples and also skeletal staining was performed. Calvaria deformations, finger anomalies, brachygnathia and short tail in experimental groups I and II were 7% and 10.8%, 13.3% and 16.6%, 7.8% and 11.7%, 10.2% and 9.2% respectively. Ten of fetuses [8.6%] in experimental group I and nine of fetuses [7.5%] in the experimental group II had eye malformations. Premature opening of one or both eyes with mild to severe exophthalmos occurred in both of the experimental groups. Also, histological examination showed deformed lens, retinal folds with undeveloped layers, corneal fold with absence of surface epithelium. This study revealed that administration of carbamazepine during embryunic period can induce eye malformations in Mice fetuses