Table 2.

Toxic effects of free heme

• Acute renal vasoconstriction

• Stimulates lipid peroxidation and generation of hydrogen peroxide

• Functions as a Damage-Associated Molecular Pattern (DAMP)

• Impairs glucose-6-phosphate dehydrogenase

• Perturbs certain cytoskeletal proteins

• Inhibits cell proliferation

• Damages mitochondria

• Induces cell death

• Activates NF-κB and induces proinflammatory cytokines

• Signals through the TLR4 receptor

• Activates the inflammasome

• Chemoattractant for leukocytes

• Promotes leukocyte adhesion to the endothelium

• Promotes formation of NETs

• Induces platelets to discharge their Weibel–Palade bodies

• Induces platelets to activate macrophages

• Induces tissue factor expression

• Thrombogenic

NETs, neutrophil extracellular traps.