title: Exacerbation of Methamphetamine Neurotoxicity in Cold and Hot Environments: Neuroprotective Effects of an Antioxidant Compound H-290/51.
abstract: In this study, we examined the influence of cold and hot environments on methamphetamine (METH) neurotoxicity in both drug-naive rats and animals previously exposed to different types of nanoparticles (NPs). Since METH induces oxidative stress, we also examined how a potential chain-breaking antioxidant H-290/51 (Astra-Zeneca, Mölndal, Sweden) affects METH-induced neurotoxicity. Exposure of drug-naive rats to METH (9 mg/kg, s.c.) at 4, 21, or 34 °C for 3 h resulted in breakdown of the blood-brain barrier (BBB), brain edema, and neuronal injuries, which all differed in severity depending upon ambient temperatures. The changes were moderate at 21 °C, 120-180 % larger at 34 °C, and almost absent at 4 °C. In rats chronically treated with NPs (SiO2, Cu, or Ag; 50-60 nm, 50 mg/kg, i.p. for 7 days), METH-induced brain alterations showed a two- to fourfold increase at 21 °C, a four- to sixfold increase at 34 °C, and three- to fourfold increase at 4 °C. SiO2 exposure showed the most pronounced METH-induced brain pathology at all temperatures followed by Ag and Cu NPs. Pretreatment with a potent antioxidant compound H-290/51 (50 mg/kg, p.o., 30 min before METH) significantly reduced brain pathology in naive animals exposed to METH at 21 and 34 °C. In NPs-treated animals, however, attenuation of METH-induced brain pathology occurred only after repeated exposure of H-290/51 (-30 min, 0 min, and +30 min). These observations are the first to show that NPs exacerbate METH-induced brain pathology in both cold and hot environments and demonstrate that timely intervention with antioxidant H-290/51 could have neuroprotective effects.
authors.affiliation: Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, SE-75185, Uppsala, Sweden, Sharma@surgsci.uu.se.
authors.forename: Hari Shanker
authors.initials: HS
authors.lastname: Sharma
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Kiyatkin
authors.forename: Ranjana
authors.initials: R
authors.lastname: Patnaik
authors.forename: José Vicente
authors.initials: JV
authors.lastname: Lafuente
authors.forename: Dafin F
authors.initials: DF
authors.lastname: Muresanu
authors.forename: Per-Ove
authors.initials: PO
authors.lastname: Sjöquist
authors.forename: Aruna
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001831:Body Temperature; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced* / Q000473:pathology; D003080:Cold Temperature / Q000009:adverse effects*; D004396:Coloring Agents / Q000493:pharmacokinetics; D003300:Copper / Q000633:toxicity*; D004357:Drug Synergism; D005070:Evans Blue / Q000493:pharmacokinetics; D006439:Hemodynamics / Q000187:drug effects; D006358:Hot Temperature / Q000009:adverse effects*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D053758:Nanoparticles / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*; D012834:Silver / Q000633:toxicity*; D012881:Skin Temperature
chemical_list: D000975:Antioxidants; D004396:Coloring Agents; C088233:H290-51; D007211:Indoles; D018696:Neuroprotective Agents; D012834:Silver; D008694:Methamphetamine; D005070:Evans Blue; D012822:Silicon Dioxide; D003300:Copper