title: Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells.
abstract: Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.
authors.affiliation: Upper Michigan Brain Tumor Center, Northern Michigan University, 1401 Presque Isle Ave, Marquette, MI, 49855, USA.
authors.forename: Johnathan E
authors.initials: JE
authors.lastname: Lawrence
authors.affiliation: College of Human Medicine, Michigan State University, 965 Fee Rd, Room A-110, Lansing, MI, 48824, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Steele
authors.affiliation: Aurora Neuroscience Innovation Institute, Aurora Health Care, 2801 W Kinnickinnic River Pkwy, Milwaukee, WI, 53215, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rovin
authors.affiliation: Upper Michigan Brain Tumor Center, Northern Michigan University, 1401 Presque Isle Ave, Marquette, MI, 49855, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Belton
authors.affiliation: Upper Michigan Brain Tumor Center, Northern Michigan University, 1401 Presque Isle Ave, Marquette, MI, 49855, USA. rwinn@nmu.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Winn
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005453:Fluorescence; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000077287:Levetiracetam; D010672:Phenytoin / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000494:pharmacology; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000077287:Levetiracetam; D014635:Valproic Acid; D010672:Phenytoin; D003907:Dexamethasone; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D003891:Desipramine; D010889:Piracetam
keywords: 5-Aminolevulinic acid; Fluorescence-guided surgery; Glioma; Photodynamic therapy; Protoporphryn IX