The mechanism of indole acetic acid cytotoxicity

The cytotoxic effect of IAA (1 mM) was examined in rat neutrophils and lymphocytes by: loss of membrane integrity (necrosis), DNA fragmentation, chromatin condensation and mitochondrial transmembrane potential (apoptosis). The following conditions were studied: (1) rat neutrophils (high peroxidase activity; (2) rat lymphocytes in the absence and presence of horseradish peroxidase; and (3) rat lymphocytes co-cultivated with rat neutrophils. Incubation of neutrophils with IAA induced loss of membrane integrity, chromatin condensation and DNA fragmentation. The same was observed in lymphocytes incubated with HRP and IAA or co-cultivated with neutrophils in the presence of IAA. Neutrophils and lymphocytes incubated with IAA presented a more pronounced depolarization of mitochondrial transmembrane potential after 12 h treatment. Incubation for 24 h in the presence of IAA (1 mM) showed increase in the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase. The addition of exogenous antioxidant enzymes (SOD and CAT) prevented the loss of cell membrane integrity induced by IAA. Therefore, the process of cell death induced by IAA involves ROS production. (C) 2004 Elsevier Ireland Ltd. All rights reserved.