title: Reduced oxidative stress in primary human cells by antioxidant released from nanoporous alumina.
abstract: Nanoporous alumina elicits different inflammatory responses dependent on pore size, such as increased complement activation and reactive oxygen species (ROS) production, on 200 versus 20 nm pores. In this study, we attempt to further modulate inflammatory cell response by loading nanoporous alumina membranes (20, 100, and 200 nm pores), with an antioxidant, Trolox, for controlled drug release. For mononuclear cells (MNC) no difference in cell response, due to pore size, was seen when cultured on nonloaded membranes. However, when exposed to membranes loaded with Trolox, 100 uM was enough to quench ROS by more than 95% for all pore sizes. Polymorphonuclear cells (PMNC) produced significantly more ROS when exposed to 20 versus 100 nm pores. For Trolox loaded membranes, this trend reversed, due to slower release of antioxidant from the 20 nm pores. Furthermore, Trolox exhibited a unique effect on PMNCs that has not previously been reported: It delayed the production of ROS in a manner distinct from antioxidant activity. The present study confirms that nanoporous alumina is a suitable vehicle for drug delivery, and that Trolox can successfully modulate the inflammatory response of both MNC and PMNCs.
authors.affiliation: Department of Medical Sciences, Uppsala University, SE-75185, Uppsala, Sweden.
authors.forename: Shiuli
authors.initials: S
authors.lastname: Pujari-Palmer
authors.affiliation: Department of Medical Sciences, Uppsala University, SE-75185, Uppsala, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Pujari-Palmer
authors.affiliation: Department of Medical Sciences, Uppsala University, SE-75185, Uppsala, Sweden.
authors.forename: Marjam
authors.initials: M
authors.lastname: Karlsson Ott
mesh_terms: D000537:Aluminum Oxide / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002839:Chromans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D016062:Porosity; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002839:Chromans; D003692:Delayed-Action Preparations; D017382:Reactive Oxygen Species; D000537:Aluminum Oxide; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
keywords: Trolox; mononuclear cells; nanoporous alumina; polymorphonuclear cells; reactive oxygen species