Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

Abstract

The cytotoxic compound hydroxyurea (HU) is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n=19) and HU-untreated (n=17) sickle cell patients and controls (n=20). The HU-treated compared with the HU-untreated patients had lower arachidonic (AA) acid level in ethanolamine, physphoglycerids (EPG) (22.9±1.2 versus 24.0±1.1%, P<0.05) serine SPG (22.13±2.2 versus 24.9±2.3%, P<0.01) phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA) and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG). In contrast, the untreated group had significantly (P<0.05) lower DHA and total n-3 compared with the controls in EPG (2.7±0.4 versus 3.2±0.6% and 4.6±0.5 versus 5.2±0.7%) and CPG (0.7±0.2 versus 1.0±0.2% and 1.2±0.2 versus 1.4±0.3). HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.