effect of MDMA and pentoxifylline drug on bad/bcl-xl gene dosage expression changes on rat liver

MDMA generally known as ecstasy, have deleterious effects on the serotonergic neurotransmitter system. Recent findings suggest that the liver and brain are major target organs of MDMA-related toxicities. Although most research is being dynamically performed on brain, however, the molecular mechanisms by which MDMA elicits adverse effects in both organs are poorly undrestood.The present study was performed to obtain evidence for molecular mechanism of apoptosis involved in MDMA-induced hepatotoxicity in rat liver after MDMAadministration. Moreover, the antagonistic effect of pentoxifylline was assessed on hepatotoxicity after MDMA administration. In this experimental study, sample size and power in each group were calculated as 10 rats with 95% confidence level and 5% confidence interval. In the study, four experimental groups were selected including Control Normal, MDMA, MDMA+PTX and PTX+MDMA. MDMA was dissolved in PBS and intraperitoneally injected three doses of 7.5mg/kg with two hours gap between doses. Pentoxyfilline also was injected as 100mg/kg, simultaneously with third dose of MDMA. After treatment, total RNA was isolated from liver tissue [5mg]. Absorbance at 260nm, 280nm and 230nm were measured and immediately reverse transcription was performed. Included target genes were BAD and BCL-XL as pro-apoptotic and anti-apoptotic gene, respectively. After set up and validation, Real-Time PCR were performed and obtaining data were statistically analyzed to determine significantly differences between groups. Using Real-Time quantitative PCR results, BCL-XL gene expression ratio significantly increased in MDMA+PTX group. Moreover, BAD gene expression ratio increased and up-regulated in PTX+MDMA group [P-value <0.001].Our study focused on molecular mechanism of MDMA in programmed cell death using gene expression quantification of a pro-apoptotic and anti-apoptoic gene in MDMA-induced hepatotoxocity. The results shown MDMA prompted apoptosis in liver and pentoxifylline protects hepatotoxicity after and befor taking MDMA

Effect of combination therapy using hypothermia and granulocyte colony-stimulating factor in a rat transient middle cerebral artery occlusion model

Stroke is the third leading cause of death. Hypothermia has been recognized as an effective method in reducing brain injury. In this study, we assessed the effects of granulocyte colony-stimulating factor [G-CSF] as a neuroprotective agent and mild hypothermia on mortality, behavioral function, infarct volume, and brain edema in Wistar rats. Forty male rats were used in five groups [eight rats in each group]: control, hypothermy, G-CSF, combination hypothermy + CSF, and sham. Rats were anesthetized by injection of chloral hydrate [400 mg/kg] intraperitoneally. Transient cerebral ischemia was induced by 60-min intraluminal occlusion of left middle cerebral artery. Hypothermia, initiated at the time of reperfusion and G-CSF was started one hour after reperfusion at a dose of 15 mg/kg subcutaneously. The motor behavior was measured using Garcia's index and animals were assigned for the assessments of infarction, brain swelling, and mortality rate. The mortality was 38.46% [control group] and reduced in other groups. Neurological deficit score of control group [40.31 +/- 1.56] was significantly lower than in treatment groups. The total cerebral infarct volume of treatment group was significantly lower than control group [43.96 +/- 44.05 mm[3]]. Treatment with hypothermy plus G-CSF [2.69 + 0.24%] could significantly reduce brain swelling volume than other treatment groups. Our major finding is that mild hypothermic treatment plus G-CSF significantly reduced mortality rate and edema and improved neurological function. The results suggest that the combination of hypothermia and G-CSF is more effectively than other treatment groups being used alone

Effects of dalteparin on structure of hippocampal neurons of rats in chronic stress

Stress is defined as any environmental change that disturbs the maintenance of brain homeostasis. Stress leads to production of pro-inflammatory cytokines that provoke neurodegenerative disorders. In the present study, we investigated the effects of dalteparin on hippocampal neuronal death induced by chronic stress in rats. The study was carried out on 60 adult male wistar rats, weighing 200- 250 gr. The rats were randomly divided into three groups: control, stress and stress + dalteparin [SD] groups. Animals in the stress and stress + dalteparin group were exposed to chronic stress for 4 weeks. Animals in the stress + dalteparin [SD] group received dalteparin [70,100 and 140 IU/kg/days i.p.] during the stress period. After the last stressor animals were sacrificed and concentration of IL-6 in serum was measured using ELISA. All animals were reperfused and their brains were processed for histological analysis through Nissl analysis. We found that the serum concentration of IL-6 was significantly higher in the CMS [Chronic Mild Stress] exposure group than in the control group [p<0.05]. Moreover, dalteparin, dose dependently decreased IL-6 concentration in the SD groups. Chronic stress also resulted in significant cell loss in hippocampal CA1, CA3 and hilus. Dalteparin markedly inhibited the decreases in number of hippocamoal CA1 and CA3 [p<0.01] and hilus [p<0.05] neurons caused by chronic stress. Chronic stress damages hippocampal CA1, CA3 and hilus neurons, and dalteparin protects hippocampus from damage induced by chronic stress