High dose of N-acetylcysteine increase H₂O₂ and MDA levels and decrease GSH level of HUVECs exposed with malaria serum

Dysfunction of endothelial cells in severe malaria may result from excessive activation of tumor necrosis factor (TNF)-α which leads to an increase in production of reactive oxygen species (ROS) and decrease of antioxidant level of endothelial cells. To investigate the effect of N-acetylcysteine (NAC) on hydrogen peroxide (H₂O₂), malondialdehyde (MDA) and glutathione (GSH) levels produced by endothelial cells exposed with serum of malaria falciparum patient, an in vitro model of human umbilical vein endothelial cells (HUVECs) culture was used. Sample groups were normal HUVECs (group A), HUVECs that was exposed with malaria serum without any treatment (group B), HUVECs that were exposed with malaria serum and treated with NAC 2μM (group C), HUVECs that were exposed with malaria serum and treated with NAC 4μM (group D), and HUVECs that were exposed with malaria serum and treated with NAC 8μM (group E). The level of MDA was measured by thio-barbituric acid reaction assay and H₂O₂ level was measured by NWLSS™ Hydrogen Peroxyde/Peroxydase Assay kit. The level of GSH was determined by using NWLSS™ Glutathione Assay kit. The level of H₂O₂ and MDA decreased after administration of low dose of NAC. Unfortunately, increased H₂O₂ and MDA levels were found on HUVECs treated with high dose of NAC (8μM). There was a positive correlation between NAC dose and H₂O₂ level (r= 0,603) and between NAC dose and MDA level (r= 0,721). A significant decreased level of GSH was found on HUVECs treated with high dose of NAC (p = 0,023). It can be concluded that the use of high dose of NAC as supportive therapy in severe malaria infection must be taken carefully.