Effects of antioxidants on drug-induced glutathione instability and lipid peroxidation in erythrocytes of sickle cell patients
AbstractGlutathione (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 á - 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 á - 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 á - 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 á - tocopherol did not reduce this post – APHZ lipid peroxidation level significantly (p > 0.05) as the post APHZ + ascorbic acid and post – APHZ + á - 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, á - 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, á - 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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