The cobalt atom of hydroxocobalamin binds cyanide and nitric oxide and hydroxocobalamin attenuates vascular responses to NO in vitro .

Treatment with hydroxocobalamin before or after giving LPS attenuates LPS-induced hypotension and increases in plasma RNI and enhances LPS-induced urinary excretion of RNI. Hydroxocobalamin (20 mg/kg i.p.) given to Swiss-Webster mice 30 min before giving LPS (16 mg/kg i.p.) decreases the 24-hr mortality of LPS from 80 to 50% and the 36- and 96-hr mortality from 100 to 60% (hydroxocobalamin).
More than 60% of the mice administered 35 mg/kg (0.63 mmol/kg) of NaSH (LD90) survive (at 24 h) when hydroxocobalamin (0.25 mmol/kg) is given after NaSH administration whereas less than 15% of the mice survive without hydroxocobalamin. Hydroxocobalamin (50–100 μM) or cobalt (50–100 μM) also preventes hepatocyte cytotoxicity induced by NaSH (500 μM). Furthermore, adding hydroxocobalamin 60 min later than NaSH still shows some protective activity.