The Potential of Leucomethylene Blue in Methemoglobinemia Treatment: A New Hope for Patients with G6PD?

Methylene blue (MB) has been routinely used to treat methemoglobinemia. In the body, MB is reduced to leucomethylene blue (LMB) by NADPH-dependent methemoglobin (MetHB) reductase, and then LMB reduces Fe3+ to Fe2+. In glucose-6-phosphate dehydrogenase (G6PD) deficiency, NADPH is not produced sufficiently to protect erythrocytes against oxidative stress and to take part in relevant biochemical reactions. Since MB is an oxidative agent, its administration in individuals with G6PD deficiency leads to an increased risk of hemolysis through oxidative stress and even death. Therefore, its administration has been prohibited from treating methemoglobinemia in G6PD patients. As an antioxidant and direct reducing agent for Fe3+, LMB may be prescribed for treating MetHB in patients with G6PD deficiency. Considering the biochemical process of turning MB into LBM and the reducing nature of LMB, it seems LMB is a safer drug than MB in treating methemoglobinemia. LMB can even be administrated in other treatments without any concern about increasing oxidative stress, exacerbating the inflammation. Proof-ofconcept experimental and clinical trials could substantiate this hypothesis.