ANTIOXIDANT–MEDIATED AMELIORATION OF DRUG – INDUCED OXIDATIVE STRESS AND METHAEMOGLOBINAEMIA IN G6PD – DEFICIENT AND SICKLE ERYTHROCYTES.
Aloh, G. S, *Obeagu, Emmanuel Ifeanyi, Okoroiwu, I.L., Odo, Christian Emeka, Odo Matthew Chibunna, Kanu,S.N, Elemchukwu, Q., Okpara,K.E., Ugwu, Getrude Uzoma,
ABSTRACT
This study assessed the effects of two antioxidants – ascorbic acid and
α- tocopherol – on the methaemoglobinaemia induced by an oxidant
drug, acetylphenylhydrazine (APHZ) on three erythrocyte types.
Oxidative stress was induced in the control, glucose- 6 – phosphate
dehydrogenase – deficient (G6PD –deficient) and sickle erythrocytes
(SEs) with 5mg of APHZ per ml of whole venous blood. Prior to
APHZ treatment, the mean methaemoglobin (MetHb) levels were 0.34
+ 0.06 mgMetHb, 0.42 + 0.03 mgMetHb, and 0.66 + 0.04 mgMetHb in
the control, G6PD – deficient and SEs respectively. After APHZ treatments, the mean
MetHb level of the control erythrocytes did not change, while those of the G6PD – deficient
and SEs rose significantly (p < 0.05) to 0.66 + 0.01 mgMetHb and 0.76 + 0.08 mgMetHb
respectively. Post – APHZ + ascorbic acid in the reaction mixture, the mean MetHb levels
were significantly (p < 0.05) scaled down to 0.33 + 0.09 mgMetHb in the control, 0.64+ 0.09
mgMetHb in the G6PD – deficient and 0.67 + 0.04 mgMetHb in the SEs respectively. α- Tocopherol had a more profound effect as the mean MetHb levels went down to 0.29 + 0.08
mgMetHb, 0.42 + 0.02 mgMetHb and 0.40 + 0.05 mgMetHb respectively. This study
indicates that MetHb is present in red cells even in the absence of exogenous oxidant
challenge, and that its level rises significantly in the G6PD –deficient and sickle erythrocytes
when subjected to oxidative stress. α- Tocopherol was found to be more effective in
counteracting drug – induced oxidative stress and the attendant methaemoglobinaemia than
ascorbic acid. Based on the results of this study, co – administration of, or following, oxidant
drugs with an effective antioxidant, such as α- tocopherol, is advisable as it will reduce
oxidative stress, the attendant methaemoglobinaemia, and its consequences.
Keywords: Antioxidants, methaemoglobin, oxidative stress , acetylphenylhydrazine.
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