Antioxidants may contribute in the fight against ageing: an in vitro model.

摘要: Elderly humans have altered cellular redox levels and dysregulated immune responses, both of which are key events underlying the progression chronic degenerative diseases ageing, such as atherosclerosis Alzeimer's disease. Poorly maintained lead to elevated activation nuclear transcription factors NFkB AP-1. These co-ordinately responsible for a huge range extracellular signalling molecules inflammation, tissue remodelling, oncogenesis apoptosis, progessess that orchestrate many processess associated with ageing. It is now clear endogenous anti-oxidants GSH decrease age. This study aimed investigate potential exogenous influence inflammatory responses ageing process itself. We investigated dietary antioxidant, quercetin, reverse age related influences depletion oxidative stress using in vitro human umbilical vein endothelial cells (HUVEC) skin fibroblast (HSF) cell models. Oxidative stress-induced were Phorbol 12-myristate 13-acetate (PMA)-induced model. As measured sensitive HPLC fluorescence method, HUVEC was depleted by addition L-buthionine-[S,R]-sulfoxiniine (BSO), gamma-glutamylcysteine synthetase inhibitor, culture medium at concentration 0.25 mM. Time course studies revealed half-life 4.6 h HUVEC. BSO 24 led slight increase intracellular adhesion molecule - 1 (ICAM1) expression prostaglandin E2 (PGE2) secretion types cells. However, markedly enhanced PMA-induced ICAM PGE2 production Responses progressively following prolonged treatment. Inhibition showed 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H7), protein kinase C (PKC) not only abolished most ICAM-1 PGE2, production, but also eliminated depletion-enhanced PMA stimulation. enhancement inhibited supplementation quercetin. The results clearly demonstrate increased susceptibility vascular fibroblasts stimuli. may be extrapolated vivo situation providing useful model micronutrients on process. In conclusion, these data suggest antioxidants could play significant role reduction responses.