Oxidative damage increases intracellular free calcium [Ca2+]i concentration in human erythrocytes incubated with lead.
One important effect of lead toxicity in erythrocytes consists of increasing [Ca(2+)](i) which in turn may cause alterations in cell shape and volume and it is associated with cellular rigidity, hemolysis, senescence and apoptosis. In this work, we proposed the use of erythrocytes incubated with Pb(2+) to assess association of the mechanisms of lead erythrocyte oxidative damage and calcium homeostasis. Lead incubation produced an increase in [Ca(2+)](i) dose- and time-dependent, which mainly involved Ca(2+) entry mechanism. Additionally, in this in vitro model alterations similar to erythrocytes of lead-exposed workers were produced: Increase in Ca(2+) influx, decrease in (Ca(2+)-Mg(2+))-ATPase activity and GSH/GSGG ratio; increase in lipoperoxidation, protein carbonylation and osmotic fragility accompanied of dramatic morphological changes. Co-incubation with trolox, a soluble vitamin-E analog is able to prevent these alterations indicating that lead damage mechanism is strongly associated with oxidative damage with an intermediate toxic effect via [Ca(2+)](i) increase. Furthermore, erythrocytes oxidation induced with a free radical generator (APPH) showed effects in [Ca(2+)](i) and oxidative damage similar to those found in erythrocytes incubated with lead. Co-incubation with trolox prevents the oxidative effects induced by AAPH in erythrocytes. These results suggest that increase of [Ca(2+)](i) depends on the oxidative status of the erythrocytes incubated with lead. We consider that this model contributes in the understanding of the relation between oxidative damage induced by lead exposure and Ca(2+) homeostasis, the consequences related to these phenomena and the molecular basis of lead toxicity in no excitable cells.
Quintanar-Escorza
M A
MA
Departamento de Bioquímica, Facultad de Medicina, Universidad Juárez del Estado de Durango, Durango, Dgo, Mexico.
González-Martínez
M T
MT
del Pilar
Intriago-Ortega Ma
IO
Calderón-Salinas
J V
JV
D000328:Adult; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress
D007854:Lead; D002118:Calcium