Effect of isoniazid, a haem inhibitor, on globin chain synthesis in reticulocytes from non-thalassaemic and beta thalassaemic subjects.

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Abstract
The effect of isonicotinic acid hydrazide (INH), a potent haem inhibitor, on globin chain synthesis was studied in reticulocytes from the following groups of patients: four non-thalassaemic patients (group i); five .beta. thalassaemia heterozygoes (group ii); three Hb S/.beta. thalassaemia heterozygotes (group iii); an two additional patients-one with homozygous .beta. thalassaemia and the other with thallassaemia intermedia (group iv). This was done to determine whether haem inhibitors depress .alpha. globin chain synthesis. The progressive increase of INH concentration (10-40 mmol l-1) in reticulocytes from a .beta. thalassaemia heterozygote resulted in a remarkable decrease of the .alpha. and .beta. chain synthesis, ranging from 80% to 97% and from 74% to 96% of control values, respectively, and in a gradual drop of .alpha.:.beta. ratio from 1,87 to 1.38. Furthermore, in the samples incubated with 40 mmol l-1 INH, a pronounced inhibition of globin chain synthesis 77 (19%) for .alpha. chain and 67 (27%) for .beta. or .beta.s chain) and a substantial drop of the .alpha.:.beta. or .beta.s ratio in samples with INH (median 1.16) compared with that in samples without INH (median 1.70) were observed. The inhibitory effect of INH was significantly or completely corrected by adding exogenous haem. It is suggested that haem inhibition and the resulting preferential diminution of .alpha. chain synthesis could provide a new approach to the treatment of homozygous .beta. thalassaemia with an excess of detrimental free .alpha. chain in erythroid cells.