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The increment of eryptosis in lead-exposed workers has been associated with oxidative stress, having as the main mediator [Ca 2+ ] i . However, other molecules could participate as signals, such as PLA 2 and SMase, which have been proposed to increase PGE 2 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 (median = 39.1 μg/dL), and low δ-ALAD activity (median = 348 nmol of porphobilinogen/h/mL); oxidative stress with high lipid peroxidation (median = 1.31 nmol of malondialdehyde/mL) and low TAC (median = 370 mM Trolox equivalents); a higher enzymatic activity of PLA 2 (median = 518 AFU/mg) and SMase (median = 706 AFU/mg) and higher eryptosis (median = 0.92% PS externalization). Correlation and conditional probability analyses permit to associate oxidative stress and eryptosis with high PLA 2 activity. However, high SMase activity was only associated with PLA 2 activity. The role of these enzymes in the signal path to eryptosis induced by oxidative stress in lead-exposed workers is discussed., (Copyright © 2019 Elsevier Inc. All rights reserved.)