The use of cobalt chloride as a chemical hypoxia model

The use of hypoxia models in cell culture has allowed the characterization of the hypoxia response at the cellular, biochemical and molecular levels. Although a decrease in oxygen concentration is the optimal hypoxia model, the problem faced by many researchers is access to a hypoxia chamber or a CO₂ incubator with regulated oxygen levels, which is not possible in many laboratories. Several alternative models have been used to mimic hypoxia. One of the most commonly used models is cobalt chloride-induced chemical hypoxia because it stabilizes hypoxia inducible factors 1α and 2α under normoxic conditions. This model has several advantages, and currently, there is a substantial amount of scattered information about how this model works. This review describes the characteristics of the model, as well as the biochemical and molecular bases that support it. The regulation of hypoxia inducible factors by oxygen and the role of CoCl₂ are explained to understand the most accepted bases of the CoCl₂ -induced hypoxia model. The different current hypotheses that explain the establishment of hypoxic conditions using CoCl₂ are also described. Finally, based on the different observations reported in the literature, we provide a critical review about the scope and limitations of this widely used chemical hypoxia model to be informative to all researchers interested in the field.