Favism: disordered erythrocyte calcium homeostasis.
The biochemical events that take place during acute hemolysis of G6PD-deficient subjects in favism are far from being elucidated. Evidence is here reported for a constantly and heavily disordered calcium homeostasis in the erythrocytes from seven favic patients. The abnormality, ie, a significantly impaired calcium ATPase activity and a parallel marked increase of intracellular calcium levels, was characteristic of the acute hemolytic crisis although unrelated to the attendant reticulocytosis. Concomitantly, a remarkable decrease of intracellular potassium was also observed. The mean +/- SD Ca2+-ATPase activity in the favic patients was 20.8 +/- 7.8 mumol Pi/g Hb/h compared with 37.2 +/- 8.5 in the matched controls represented by 12 healthy G6PD-deficient subjects (P less than .001). The mean +/- SD intraerythrocytic calcium content was 288 +/- 158 mumol/L of erythrocytes in the favic patients as compared with 22.0 +/- 8.2 in the G6PD-deficient controls (P less than .001). The intraerythrocytic potassium content was 76.6 +/- 19.3 mmol/L of erythrocytes in the favic patients and 106.6 +/- 8.2 in the G6PD-deficient controls (P less than .001). In vitro incubation of normal and G6PD-deficient erythrocytes with divicine, a pyrimidine aglycone present in fava beans and strongly implicated in the pathogenesis of favism, reproduces most of these events, including drop of calcium ATPase, increased intracellular calcium, and leakage of erythrocyte potassium.
De Flora
A
A
Benatti
U
U
Guida
L
L
Forteleoni
G
G
Meloni
T
T
D000208:Acute Disease; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002469:Cell Separation; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D005236:Favism / Q000201:enzymology*; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008706:Methemoglobin / Q000032:analysis; D011188:Potassium / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology
D007473:Ion Channels; D011744:Pyrimidinones; C026511:divicine; D008706:Methemoglobin; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium