title: A new antioxidant compound H-290/51 attenuates nanoparticle induced neurotoxicity and enhances neurorepair in hyperthermia.
abstract: Previous reports from our laboratory show that animals treated with engineered nanoparticles derived from metals for 1 week and subjected to hyperthermia showed enhanced neurotoxicity in terms of blood-brain barrier (BBB) disruption, brain edema formation and cell injury. It appears that nanoparticle induced enhanced oxidative stress leads to increased lipid peroxidation and over-production of hydroxyl radicals are responsible for exacerbation of neurotoxicity in hyperthermia. Therefore, in this investigation, rats (after 1 week administration of Ag or Cu nanoparticles) were treated with a new antioxidant compound H-290/51 (an inhibitor of lipid peroxidation, 50 mg/kg, p.o.) before subjecting them to hyperthermia. One group of nanoparticle treated rat received H-290/51 and were kept at room temperature for comparison. Our results show that H-290/51 significantly attenuated heat stress induced BBB impairment, brain edema formation and neurotoxicity in nanoparticle treated rats. However, no significant diminution of nanoparticle induced BBB breakdown, or neurotoxicity was observed in H-290/51 treated rats kept at room temperature. These observations suggest that nanoparticles aggravate oxidative stress following hyperthermia leading to exacerbation of neurotoxicity through oxidative stress-related mechanisms, not reported earlier.
authors.affiliation: Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala, Sweden. Sharma@surgsci.uu.se
authors.forename: Hari Shanker
authors.initials: HS
authors.lastname: Sharma
authors.forename: Aruna
authors.initials: A
authors.lastname: Sharma
authors.forename: Saber
authors.initials: S
authors.lastname: Hussain
authors.forename: John
authors.initials: J
authors.lastname: Schlager
authors.forename: Per-Ove
authors.initials: PO
authors.lastname: Sjöquist
authors.forename: Daffin
authors.initials: D
authors.lastname: Muresanu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000494:pharmacology*; D005334:Fever / Q000188:drug therapy; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D053758:Nanoparticles / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D005227:Fatty Acids; C088233:H290-51; D007211:Indoles; C013584:lipid peroxidation inhibitor