Hemolysis and Metabolic Lesion of G6PD Deficient RBCs in Response to Dapsone Hydroxylamine in a Humanized Mouse Model

Abstract

Nonstandard Abbreviations. Glucose 6-phosphate dehydrogenase (G6PD), G6PD deficiency (G6PDd), pacific blue (PB), green fluorescent protein (GFP), methanol (MeOH), liquid chromatography-mass spectrometry (LC-MS), 6-phosphogluconate (6P-gluconate), monoacetyldapsone hydroxylamine (MADDS-NOH), hemoglobin (Hb), methemoglobin (MetHb), methemoglobin reductase (MR), pentose phosphate pathway (PPP), citrate phosphate dextrose adenine buffer (CPDA-1), dapsone hydroxylamine (DDS-NOH), Mediterranean variant of G6PD (Med-), humanized G6PD-deficient mouse (hG6PD Med-), pacific blue (PB)

The clinical relevance of heme detoxification by the macrophage heme oxygenase system

“…Deficiency of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the first step of the pentose phosphate pathway (PPP), is the most common inherited enzyme defect worldwide (51). In response to infection, inflammation, or increased oxidative stress from certain medications, patients with G6PD deficiency experience acute intravascular hemolysis (51), a finding that has also been recapitulated in mouse models of the disorder (52)(53)(54)(55). As the first step of the oxidative branch of the PPP, the enzymatic activity of G6PD is a major source of NADPH within cells, and therefore is critical for maintenance of redox homeostasis (56).…”