Morphine-Mediated Cytoprotection against Hemin in SK-N-SH and A172 Cells

The toxicity of free heme has been documented in several disease types. For example, in hemolytic anemias such as sickle cell disease and thalassemia, release of heme from hemoglobin followinglysis of red blood cells is known to cause cell death. In a critical care situation such as hemorrhagic injury, neuronal cell death is caused by the lysis of red blood cells, which release hemoglobin and its breakdown product hemin. Physiological levels of free heme in the blood are maintained at low levels (0.1 -1 μM) by the high binding affinity of proteins such as serum albumin, hemopexin and haptoglobin. When internalized, free heme is catabolized by heme oxygenases (HO1 and HO2 isoforms) and therefore the amount of cellular damage free heme produces is limited by the stress-responsive HO1 isoform. 

In addition to HO1 and HO2 isoform regulated cellular damage, the oxidative state of iron (from Fe²⁺ to Fe³⁺ via the Fenton reaction) within heme can produce harmful superoxide free radicals in the brain that can lead to oxidative stress, initiation of lipid peroxidation and neuronal death.Pathological conditions can increase the level of heme and iron. For example in acute conditions such as severe hemolytic crisis in sickle cell disease, heme levels can increase up to 20 μM or to greater than 200 μM (supraphysiological levels) in thalassemia. Therefore, further studies on the cross talk between neuroinflammatory mediators and iron-containing hemoproteins such as hemin are warranted.(Read more)