A New Antioxidant Compound H-290/51 Attenuates Nanoparticle Induced Neurotoxicity and Enhances Neurorepair in Hypertherm
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
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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. Keywords Nanoparticles • silver • copper • hyperthermia • blood–brain barrier • brain edema • oxidative stress • H-290/51 • neurotoxicity • neuroprotection H.S. Sharma (*), A. Sharma Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Frödingsgatan 12:28, Uppsala, SE-75421, Sweden and Neurochemistry Laboratory, Division of Neurotoxicology, National Centre for Toxicological Research/FDA, Jefferson, AR, USA e-mail: [email protected] S. Hussain and J. Schlager Applied Biotechnology Branch, Human Effectiveness Directorate, Air Force Research Laboratory, Wright-Patterson Air Force Base, OH, USA Per-Ove Sjöquist Department of Integrative Pharmacology, Astra-Zeneca Mölndal, Mölndal, Sweden D. Muresanu Department of Neurology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Romania
Introduction Effect of nanoparticles on brain function in normal conditions and following exposure to stress or trauma is still not well known (1,4–8). It appears that nanoparticles from the environment could enter into the body compartments and alter brain functions (10,17, see 21,23). Previous investigations from our laboratory show that the stress response and brain pathology following hyperthermia is aggravated in animals that received engineered nanoparticles from metals, i.e., Cu, Ag and Al prior to heat exposure (10,17). Although the physiological mechanisms of nanoparticle-induced exacerbation of brain pathology following hyperthermia are still unclear, it appears that nanoparticle-induced oxidative stress could play important roles (5–7). Nanoparticles, e.g., Cobalt, carbon tubes, quantum dots,
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