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Low membrane protein sulfhydrils but not glucose‐6‐phosphate dehydrogenase deficiency predict ribavirin‐induced hemolysis
Author(s) -
Russmann S.,
Grattagliano I.,
Palmieri V. O.,
Portincasa P.,
Bihl F.,
Palasciano G.,
Lauterburg B. H.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.216
Subject(s) - hemolysis , glutathione , erythrocyte fragility , oxidative stress , chemistry , antioxidant , glucose 6 phosphate dehydrogenase deficiency , pharmacology , glucose 6 phosphate dehydrogenase , biochemistry , medicine , endocrinology , dehydrogenase , enzyme
Purpose Hemolysis is a frequent adverse effect of ribavirin (RBV). Oxidative stress has been suggested to play a role, but mechanisms and predictive risk factors are unknown. Methods : Markers of redox status were determined in erythrocytes from hepatitis C infected patients with and without G6PD‐deficiency before and during RBV treatment, and erythrocytes were incubated with RBV and dipyridamole, diethylmaleate or glutathione ester. Results : 5 out of 30 patients developed major RBV‐induced hemolysis, which was associated with a more pronounced increase in thiobarbituric acid reactive substances (+22.5 vs. +9.4 nmol/gHb, p<.01 and decrease in free glutathione (‐1.9 vs. ‐0.2 μmol/gHb, p<.001) than in patients with minor hemolysis. All patients with major hemolysis already had lower membrane protein sulfhydrils (28.2±0.8 vs. 36.6±0.4 nmol/mg, p<.001) before treatment. G6PD deficient patients had only minor hemolysis. In the in‐vitro incubations, diethylmaleate enhanced the RBV‐induced decrease of glutathione, protein sulfhydrils and osmotic hemolysis, whereas glutathione ester and dipyridamole prevented these changes. Conclusion : The data indicate that low membrane protein sulfhydrils prior to therapy but not G6PD deficiency predict RBV‐induced major hemolysis. In‐vitro, glutathione ester and dipyridamole reduce erythrocyte oxidative stress and prevent RBV‐induced increase in osmotic fragility, suggesting that these compounds may also decrease the risk of hemolysis in patients. Clinical Pharmacology & Therapeutics (2004) 75 , P57–P57; doi: 10.1016/j.clpt.2003.11.216