کورکومین با فعال سازی مسیر nrf2/nfkb به‫ صورت محدود باعث مهار استرس اکسیداتیو القا شده توسط دی-2-اتیل هگزیل فتالات در سلول‫های بنیادی مزانشیم مغز استخوان شد‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬

هدف: زردچوبه حاوی مقدار زیادی کوکومین (cur) است که اثر آنتی اکسیدانتی قوی دارد. از دی-2-اتیل هگزیل فتالات (dehp) در محصولات پلی ونیل کلرید (pvc) استفاده می شود که امکان رها شدن و ورود آن به مایعات زیستی در طی درمان‫های پزشکی وجود دارد. dehp باعث القای استرس اکسیداتیو در سلول‫های بنیادی مزانشیم مغز استخوان (bmscs) می شود، لذا هدف این مطالعه بررسی اثر cur بر استرس اکسیداتیو ناشی از dehp در bmscs می باشد. مواد و روش‫ها: درصد زنده مانی bmscs بعد از پاساژ سوم در حضور غلظت‫های 0.05 تا 5 میکرومولار cur برای مدت 4 روز بررسی شد. سپس از غلظت 0.1 میکرومولار cur برای بررسی در صد زنده مانی و تکثیری سلول‫ها، غلظت مالون دی آلدئید (mda)، ظرفیت تام آنتی اکسیدانت (tac)، فعالیت آنزیم‫های کاتالاز و سوپر اکسید دیسموتاز (sod)  و همچنین بیان ژن‫های nfkb و nrf2 به‫صورت مجزا و در حضور غلظت‫های 100 و 500 میکرو مولار dehp درمدت 4 و 8 روز  استفاده شد. نتایج: غلظت منتخب cur در مدت 4 روز باعث افزایش توانائی تکثیر سلول‫ها شد. این غلظت توانست در مدت 4 و 8 روز اثر سمی dehp را مرتفع ساخته و همچنین باعث کاهش غلظت mda و افزایش فعالیت آنزیم‫های کاتالاز و sod،  به‫خصوص در 8 روز شود. با توجه به افزایش tac، این ترکیب گیاهی توانست بیان nfkb را کاهش و بیان nrf2 را افزایش دهد. نتیجه گیری: cur از طریق مسیر nrf/nfkb اثر اکسیداتیو القا شده توسط dehp را کاهش داد. لذا برای کم کردن اثر dehp در بیماران، می‫توان از زردچوبه استفاده نمود.

curcumin partially prevented oxidative stress induced by dehp in bone marrow mesenchymal stem cells through activation of nrf2/nfkb pathway

aim: turmeric contains a high amount of curcumin (cur), which exhibits strong antioxidant activity. cur binds to antioxidant response elements for gene, thus suppressing reactive oxygen species (ros). reactive oxygen species are short-lived, highly electrophilic molecules. when intracellular antioxidants are reduced or ros accumulate excessively, it brings about the imbalance in the redox state which leading to oxidative stress. dehp consists of a pair of eight-carbon esters linked to a benzene-dicarboxylic acid ring with chemical formula of c24h38o4. dehp is used as a plasticizer in many polyvinyl chloride products, especially in medical devices such as intravenous bags and tubing, umbilical artery catheters, blood bags, infusion tubing, enteral nutrition feeding bags, nasogastric tubes and dialysis bags. due to non-covalent binding to the plastic products, dehp leaches into biological fluids during medical treatment causing contamination. there is ample evidence that dehp induces oxidative stress and causes apoptosis in cells. therefore, the study aimed to investigate the effects of cur on dehp-induced oxidative stress in bone marrow mesenchymal stem cells (bmscs), as dehp has been found to induce oxidative stress in bmscs. materialand methods: rat bmscs was extracted and after the 3rd passage, their cell viability and proliferation were examined in the presence of various concentrations (0.05,0.1, 0.25, 1, 2.5 and 5 μm) of cur for a period of 4 days. subsequently, a concentration of 0.1 μm cur was chosen for further assessment of viability and proliferation abilities (measured by population doubling number (pdn)), total protein, malondialdehyde (mda), total antioxidant capacity (tac), catalase and superoxide dismutase (sod) activity as well as the expression of nfkb and nrf2 both individually and in conjunction with 100 or 500 μm of dehp (chosen based on previous study) for durations of 4 and8 days. the data underwent statistical analysis with p<.05 considered as the minimum level of significance. results: concentrations of 0.05, 0.1, and 0.25 μm of cur were found to have no effect on the viability (p<0.05) of the bmscs but significantly increased proliferation ability (p<0.0001). conversely, concentrations of 1, 2.5, and 5 μm of cur significantly reduced viability (p<0.0001). the concentration of 0.1 μm was chosen for further analysis based on viability tests and pdn analysis. this selected concentration notably increased bmscs proliferation after 4 days, while higher concentrations (1, 2.5, and 5 μm) reduced both viability and proliferation. furthermore, this concentration counteracted the effects of dehp at both day 4 and day 8 by reducing mda levels and increasing tac levels as well as catalase and sod activity - particularly at day 8 compared to the dehp-treated groups. additionally, cur was found to reduce nfkb expression while increasing nrf2 expression in bmscs.conclusion: curcumin mitigated oxidative stress induced by dehp through the nrf/nfkb pathway. moreover, it enhanced the cell viability and proliferation capacity of bmscs in the presence of dehp. therefore, patients undergoing hemodialysis and blood transfusion, who may be exposed to dehp from medical devices like tubes and other plastic products, should consider consuming turmeric to counteract the oxidative impact of this chemical.