Dose-Dependent Effects of Astaxanthin on Ischemia/Reperfusion Induced Brain Injury in MCAO Model Rat.

Excitotoxicity and oxidative stress are central to the pathology of the nervous system, and inhibition of excitotoxicity induced by glutamate is one of the therapeutic goals determined for stroke. The present study aimed to investigate the effects of Astaxanthin, a potent natural antioxidant, on complications caused by acute cerebral stroke. In this research, 60 male Wistar rats were used which were divided into 5 groups as follow: (1) the sham group (vehicle), (2) the ischemic control group (vehicle), and the ischemic groups treated by Astaxanthin with doses of 25, 45, and 65 mg/kg. In the ischemic groups, ischemic model was performed by middle cerebral artery occlusion (MCAO) method, and the Astaxanthin administration was carried out after the artery occlusion and before opening the artery. The obtained results indicated that Astaxanthin could significantly reduce stroke volume, neurological deficits, and lipid peroxidation. Moreover, it was able to restore total oxidant status (TOS) and caspase 3 level to the normal level. The activity of antioxidant enzyme glutathione peroxidase (GPX), and the expression of catalase, GPx and nuclear factor kappa B (NFκb) genes, which were reduced after ischemia, were increased. This phenomenon was particularly pronounced for glutamate transporter 1 (GLT-1). Furthermore, Astaxanthin decreased the augmented pro-apoptotic gene Bax and restored the reduced Bcl2 expression to the normal level. Significant effects on the P53 and PUMA expression were not observed. Overall, the medium dosage of Astaxanthin appears to be more effective in reducing the complications of ischemia, particularly on our major study endpoints (stroke volume and neurological defects). Longer studies with a more frequent administration of Astaxanthin are required to better understand the precise mechanism of Astaxanthin.

Pro-Apoptotic and Anti-Angiogenesis Effects of Olive Leaf Extract on Spontaneous Mouse Mammary Tumor Model by Balancing Vascular Endothelial Growth Factor and Endostatin Levels.

It has been proven that olive associated products such as olive leaf extract (OLE) causes significant reduction in cancer cells viability and proliferation. Female BALB/c adult mice were divided into four groups. Three days prior to oral treatments, tumors were transplanted. First group were treated with distilled water and other three groups were received, respectively, 75, 150, and 225 mg/kg/day of OLE for three weeks. For assessment of anti-angiogenesis and pro-apoptotic effect of OLE on tumor tissue, tumor volume, cell mitosis and apoptosis, and also vascular endothelial growth factor (VEGF) and endostatin levels were assessed. OLE treatment with 150 and 225 mg/kg/day lead to significant reduction in tumor volume and cell mitosis compared with the control group, while the same doses significantly increase tumor cell apoptosis. OLE treatment with 150 mg/kg/day increase endostatin levels, while the same dose did not significantly decrease VEGF levels. The VEGF level is significantly reduced by the treatment with OLE 225 mg/kg/day for three weeks. Although, further studies are needed to clarify anti-angiogenesis and anti-apoptotic mechanism of OLE, consumption of OLE polyphenols after tumor transplantation reduced spontaneous mouse mammary tumor growth.

Therapeutic Potential of Pretreatment with Allograft Sertoli Cells Transplantation in Brain Ischemia by Improving Oxidative Defenses.

Brain ischemia is one of the most common causes of death and disability worldwide, which usually happens through diminished blood supply to the tissue. Cell therapy and treatments using trophic factors are some of the new methods to protect brain cells against damage. Specific properties of Sertoli cells (SCs) make them suitable for improving neurological disorders. This study is to evaluate possible neuroprotective effects of SCs transplantation on ischemic damage. Rats were divided into three experimental groups including sham, control, and SCs-treated group. In this study, SCs were isolated from testis of rats and were transplanted into the right striatum by using stereotaxic surgery. After a week, ischemic surgery was performed. Twenty-four hours later, rats were scarified and different regions of the brain including the cortex, the piriform cortex-amygdala (Pir-Amy), and the striatum were collected and preserved in - 80 °C for further investigations. This study demonstrates that SCs transplantation can reduce brain ischemia deficits and increase superoxide dismutase (SOD) and catalase (CAT) activities. It also decreases malondialdehyde production, which is the main product of lipid peroxidation. SCs improve ischemic behavioral disorder and reduce brain edema, blood-brain barrier permeability, and infarct volume. It seems that transplantation of SCs can protect neural cells against ischemia by decreasing oxidative stress.