Effects of Antioxidants on Drug-Induced Glutathione Instability and Lipid Peroxidation in Erythrocytes of Sickle Cell Patients
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Abstract
Glutathione (GSH) instability leading to its depletion, and enhanced lipid peroxidation, are associated with the pathogenesis, progression and therapy of many diseases / disease conditions – including sickle cell disease. In this study, the effects of two antioxidants, ascorbic acid and α - tocopherol, on GSH instability and lipid peroxidation were assessed before inducing oxidative stress with acetylphenylhydrazine (APHZ) (Pre-APHZ), post APHZ, and post – APHZ followed with ascorbic acid and α - tocopherol respectively. The mean pre-APHZ GSH concentration of 26 + 2.32 mg/100ml was significantly (p < 0. 05) reduced to 13 + 1.98mg/100ml post – APHZ. This post – APHZ value was insignificantly (p > 0.05) elevated to 16 + 1.82 mg/100ml when treated with ascorbic acid, while α - tocopherol significantly (p < 0.05) elevated it to 22 + 2.24 mg/100ml. APHZ significantly (p < 0.05) elevated the level of lipid peroxidation (MDA) from 210.91 + 23.43 nmol/hr (pre-APHZ) to 284 + 31.00 nmol/hr post- APHZ. Both ascorbic acid and α - tocopherol did not reduce this post – APHZ lipid peroxidation level significantly (p > 0.05) as the post APHZ + ascorbic acid and post – APHZ + α - tocopherol levels of MDA
remained at life – threatening levels of 266.70 + 31.00 nmol/hr and 238.50 + 26.37 nmol/hr respectively. In this study, α - tocopherol was a better antioxidant than ascorbic acid but it appears that elevation of GSH level per se is not enough to arrest drug – induced lipid peroxidation in sickle cell patients and 238.50 + 26.37 nmol/hr respectively. In this study, α - tocopherol was a better antioxidant than ascorbic acid but it appears that elevation of GSH level per se is not enough to arrest drug – induced lipid peroxidation in sickle cell patients.
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