RESUMO
Chronic lead exposure can generate pro-oxidative and pro-inflammatory conditions in the blood, related to high platelet activation and aggregation, altering cell functions. We studied ADP-stimulated aggregation and the oxidant/antioxidant system of platelets from chronically lead-exposed workers and non-exposed workers. Platelet aggregation was low in lead-exposed workers (62 vs. 97%), who had normal platelet counts and showed no clinical manifestations of hemostatic failure. ADP-activated platelets from lead-exposed workers failed to increase superoxide release (3.3 vs. 6.6 µmol/g protein), had low NADPH concentration (60 vs. 92 nmol/mg protein), high concentration of hydrogen peroxide (224 vs. 129 nmol/mg protein) and high plasma PGE2 concentration (287 vs. 79 pg/mL). Altogether, those conditions, on the one hand, could account for the low platelet aggregation and, on the other, indicate an adaptive mechanism for the oxidative status of platelets and anti-aggregating molecules to prevent thrombotic problems in the pro-oxidant and pro-inflammatory environment of chronic lead exposure.
Assuntos
Chumbo , Agregação Plaquetária , Humanos , Chumbo/toxicidade , Plaquetas , Espécies Reativas de Oxigênio/metabolismo , Oxirredução , Difosfato de Adenosina/metabolismoRESUMO
Lead intoxication can generate pro-inflammatory conditions that have been proposed to be associated with cell injuries and oxidative stress. The pro-inflammatory state can participate in the pathophysiology of this toxicity to generate immune response dysfunctions, which could condition the presence of clinical manifestations and susceptibility to infections already described in lead-exposed patients. In the present work, we study workers of a battery recycler factory (nâ¯=â¯24) who are chronically exposed to lead and compared them with non-lead exposed workers (nâ¯=â¯17). Lead-exposed workers had high lead concentrations in blood (med 69.8 vs. 1.7⯵g/dL), low δ-ALAD activity (med 149 vs. 1100â¯nmol PBG/h/mL), high lipid peroxidation (med 0.86 vs. 0.69â¯nmol/mL) and high erythrocytes apoptosis (med 0.81 vs. 0.50% PS externalization) in relation to non-lead exposed workers. Also, lead-exposed workers had a high incidence of signs and symptoms related to lead intoxication and a higher frequency of infections. The higher leukocyte apoptosis (med 18.3 vs. 8.2% PS externalization) and lower basal TNF-α concentration (med 0.38 vs. 0.94â¯pg/mL) in lead-exposed workers imply an immune response dysfunction; however, there was no difference in the TNF-α concentration when leukocytes were stimulated with lipopolysaccharide in whole blood (med 44 vs. 70â¯pg/mL), suggesting that lead-exposed workers might develop adaptation mechanisms to reduce basal TNF-α release through downregulation processes proposed for this cytokine.
Assuntos
Apoptose/efeitos dos fármacos , Intoxicação por Chumbo/patologia , Leucócitos/patologia , Exposição Ocupacional , Fator de Necrose Tumoral alfa/sangue , Adulto , Estudos de Casos e Controles , Eritrócitos/patologia , Feminino , Humanos , Imunidade/efeitos dos fármacos , Chumbo/sangue , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Sintase do Porfobilinogênio/sangueRESUMO
The increment of eryptosis in lead-exposed workers has been associated with oxidative stress, having as the main mediator [Ca2+]i. However, other molecules could participate as signals, such as PLA2 and SMase, which have been proposed to increase PGE2 and ceramides, both involved in the increment of PS externalization due to osmotic stress. To study the role of these enzymes in lead intoxication, we studied 30 lead exposed workers and 27 non-lead exposed individuals. We found, compared to non-exposed subjects, lead intoxication characterized by high blood lead concentration (medianâ¯=â¯39.1⯵g/dL), and low δ-ALAD activity (medianâ¯=â¯348â¯nmol of porphobilinogen/h/mL); oxidative stress with high lipid peroxidation (medianâ¯=â¯1.31â¯nmol of malondialdehyde/mL) and low TAC (medianâ¯=â¯370â¯mM Trolox equivalents); a higher enzymatic activity of PLA2 (medianâ¯=â¯518 AFU/mg) and SMase (medianâ¯=â¯706 AFU/mg) and higher eryptosis (medianâ¯=â¯0.92% PS externalization). Correlation and conditional probability analyses permit to associate oxidative stress and eryptosis with high PLA2 activity. However, high SMase activity was only associated with PLA2 activity. The role of these enzymes in the signal path to eryptosis induced by oxidative stress in lead-exposed workers is discussed.