ABSTRACT
3-4, methylenedioxymethamphetamine [MDMA] causes apoptosis in nervous system and several studies suggest that oxidative stress contributes to MDMA-induced neurotoxicity. The aim of this study is to examine the effects of N-acetyl-L-Cystein [NAC] as an antioxidant on MDMA-induced apoptosis. 21 Sprague dawley male rats [200-250mg] were treated with MDMA [2x0,5mg/kg] or MDMA plus NAC [100mg/kg IP for 7 day]. After last administration of MDMA, rats were killed, cerebellum was removed and Bax and Bcl-2 expression was assessed by western blotting method. The results of this study showed that MDMA causes up-regulation of Bax and down-regulation of Bcl-2 and NAC administration attenuated MDMA-induced apoptosis. The present study suggests that NAC treatment may improve MDMA-induced neurotoxicity.
Subject(s)
Male , Animals, Laboratory , Neurotoxicity Syndromes/prevention & control , Cerebellum , Neuroprotective Agents , N-Methyl-3,4-methylenedioxyamphetamine/adverse effects , Oxidative Stress , Antioxidants , Apoptosis , Rats, Sprague-DawleyABSTRACT
Central and peripheral neuropathies are the most common side effects of Diabetes Mellitus [DM]. The exact mechanisms of diabetic neurotoxicity are still unknown. Recently oxidative stress is introduced as one of the factors for diabetics' neuropathies. Antioxidants also used as therapeutic agents to reduce the side effects of diabetes. In the present research the antioxidant effects of total and flavonoid extracts of Cusseta lehmaniana Bunge on high glucose inducted Pc12 were studied. PC12 cell line treated with high glucose was used. Total and flavonoid extract of C. lehmaniana Bungs were prepared. PC12 cells treated with 6X fold high glucose concentration exposed to extracts. Antioxidant activity of extracts, cell viability and apoptosis were studied by DPPH, MTT, Annexin staining and Western Blotting respectively. The MTT result showed 50æg/ml of flavonoid extract and 100æg/ml of total C. lehmaniana Bungs extract increased cell viability after 3 hours pretreatment. DPPH assay demonstrated 50 æg/ml flavonoid extract can increased radical scavenging inhibits compare with ascorbic acid. Several assays were used for evaluated of anti apoptotic effect such as: Annexin, SubG1and Western blotting for expression of Bax protein. Based on our findings, it is concluded that both total and flavonoid extract of C. lehmaniana Bungs have the potential to protect PC12 cells against glucose neurotoxicity by reducing apoptosis via increased Bax expression protein
ABSTRACT
Tumor necrosis factor alpha [TNF-alpha] is a primary mediator of immune regulation and might be required in the early stages of DC development from CD34[+] cells. However, details of optimal timing of exposure to TNF-alpha in DC development process in monocytes or non-purified hematopoitic cells are still lacking and clear benefits of this approach to the development of DCs remain to be validated. To evaluate the effect of early and late exposure to TNF-alpha on DC development from non-purified cord blood mononuclear cells. To define the effects of early exposure to TNF-alpha on cord blood mononuclear cells, we cultured UCB-MNC in the presence of SCF, Flt3L, GM-CSF and IL-4 for 14 days and matured them for an extra 4 days. TNF-alpha was added on day 0, 7 and 14 in TNF-alpha [+] group, and only on day 14 in TNF-alpha [-] group where it was used only as a maturation factor. Immediate exposure to TNF-alpha was shown to: [1] enhance the survival of cells in the first week of culture; [2] produce mature DCs with higher maturation markers [CD80, CD83, CD86 and HLA-DR]; and [3] increase secretion of IL-12 by mature DCs. In contrast, delayed exposure to TNF-alpha stimulate mature DCs with less purity producing a high level of IL-10 and a low level of IL-12. We developed a simple, easy and cost effective method to generate DCs from non-fractionating mononuclear cells in this study. Also we confirm the presence of a large number of functional DCs under inflammatory conditions, where local concentrations of TNF-alpha were high