title: Cobalt supplementation promotes hypoxic tolerance and facilitates acclimatization to hypobaric hypoxia in rat brain.
abstract: In the present study, we report the molecular mechanisms of action by cobalt in facilitating acclimatization to hypobaric hypoxia using male Sprague-Dawley rats as the model system. We determined hypoxic gasping time and survival time as a measure to assess the degree of tolerance of animals to hypobaric hypoxia by exposing the animals to an altitude of 10,668 m. Oral administration of cobalt chloride (12.5 mg Co/kg body weight, BW, for 7 days) increased gasping time and hypoxic survival time by 3 to 4 times compared to the control animals. This could be attributed to an increased expression and the DNA binding activity of hypoxia inducible transcriptional factor (HIF-1alpha) and its regulated genes, that is, erythropoietin (EPO), vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1), and nitric oxide synthase (NOS) levels. This in turn leads to better oxygenation, oxygen delivery, glucose transport, and maintenance of vascular tone, respectively, under oxygen-limited conditions. This was further confirmed by lower levels of lactate dehydrogenase (LDH) activity and lactate in the brain of cobalt + hypoxia group compared with animals exposed to hypoxia. Glucose levels also increased after cobalt supplementation. The findings of the study provide a basis for the possible use of cobalt for facilitating acclimatization to hypoxia and other conditions involving oxygen deprivation.
authors.affiliation: Defence Institute of Physiology and Allied Sciences, Timarpur, India. shri_kalpana@yahoo.com
authors.forename: Kalpana
authors.initials: K
authors.lastname: Shrivastava
authors.forename: M Sai
authors.initials: MS
authors.lastname: Ram
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: S S
authors.initials: SS
authors.lastname: Singh
authors.forename: G
authors.initials: G
authors.lastname: Ilavazhagan
mesh_terms: D000064:Acclimatization / Q000187:drug effects*; D000222:Adaptation, Physiological / Q000187:drug effects; D000532:Altitude Sickness / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control*; D000818:Animals; D003035:Cobalt / Q000008:administration & dosage / Q000494:pharmacology*; D004921:Erythropoietin / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D002534:Hypoxia, Brain / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D003035:Cobalt; D019001:Nitric Oxide Synthase; C018021:cobaltous chloride