Loss of Erythrocyte Deformability under Oxidative Stress is caused by Protein Oxidation with Consequent Degradation Rather than by Lipid Peroxidation

Aims: Loss of erythrocyte deformability under oxidative stress is poorly understood. The present study aimed to determine which of the detrimental effects of oxidant stress, namely, lipid peroxidation or protein degradation, is responsible for loss of erythrocyte deformability.
Methodology: Different natural and synthetic antioxidants were tested for their protective effects on erythrocyte deformability, lipid peroxidation and protein degradation after exposure to H2O2. Antioxidants used included α-Tocopherol (vitamin E), Butylated Hydroxytoluene (BHT), vitamin C, PNU-101033E, carbon monoxide (CO) and selected flavonoids and herbal extracts.
Results: Exposure of human erythrocytes in vitro to H2O2 caused loss of deformability, lipid peroxidation and protein degradation. Pre-incubation of erythrocytes with vitamin E, BHT, vitamin C, PNU-101033E, the flavonoids rutin and morin and herbal extracts of Ferula hermonis, Hibiscus sabdariffa, Teucrium polium, prevented lipid peroxidation caused by H2O2 but did not prevent loss of erythrocyte deformability, nor protein degradation. CO, the flavonoid quercetin and herbal extracts of Nigella sativa and Allium sativumprevented both lipid peroxidation and protein degradation, but also prevented loss of erythrocyte deformability. The flavonoid 3,5,7-trihydroxy-4’-methoxy flavone-7-rutinoside prevented both protein degradation and loss of deformability, with no effect on lipid peroxidation. Vitamin C, unexpectedly, caused a significant increase in loss of erythrocyte deformability induced by H2O2 in parallel to the increased rate of protein degradation.
Conclusion: These results suggest that protein degradation rather than lipid peroxidation is responsible for loss of erythrocyte deformability under oxidative stress. Also that lipid peroxidation and protein degradation occur by independent mechanisms. This study should initiate a search for potential drugs that can prevent protein oxidation as well as lipid peroxidation, thereby acting in the prevention of adverse hemorheological consequences in disease states associated with oxidative stress. Caution should be exercised in the therapeutic use of vitamin C, especially under oxidant stress.