Cobalt supplementation promotes hypoxic tolerance and facilitates acclimatization to hypobaric hypoxia in rat brain.
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.
Shrivastava
Kalpana
K
Defence Institute of Physiology and Allied Sciences, Timarpur, India. shri_kalpana@yahoo.com
Ram
M Sai
MS
Bansal
Anju
A
Singh
S S
SS
Ilavazhagan
G
G
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
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