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.