Effects of 2-ethylhexanoic acid on the production of reactive oxygen species in human polymorphonuclear leukocytes in vitro

• Published in: Toxicology letters Vol. 117; no. 1; pp. 79 - 84
• Main Authors: Pennanen, Sirpa M.A, Heiskanen, Kaisa M, Savolainen, Kai M, Komulainen, Hannu
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 30-09-2000; Amsterdam Elsevier Science
• Subjects: 2-Ethylhexanoic acid; Biological and medical sciences; bis(2-ethylhexyl) phthalate; Caproates - pharmacology; Carcinogenesis, carcinogens and anticarcinogens; Cell Survival - drug effects; Chemical agents; Chemical and industrial products toxicology. Toxic occupational diseases; Dose-Response Relationship, Drug; Humans; Medical sciences; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - metabolism; Polymorphonuclear leukocytes; Protein Kinase C - drug effects; Protein Kinase C - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Toxicology; Tumors; Various organic compounds; 2-Ethylhexanoic acid; Polymorphonuclear leukocytes; Reactive oxygen species; Human; Carcinogen; Oxidative stress; Carboxylic acid; Aliphatic compound; Leukocyte; Toxicity; Mechanism of action; In vitro; Peroxisome proliferator
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(00)00243-5

2-Ethylhexanoic acid (2-EHA), is an industrial chemical and a toxic biotransformation product of the plasticizer di(2-ethylhexyl)phthalate. Its immunological effects are unknown. 2-EHA resembles structurally C18 fatty acids, which are known activators of respiratory burst in human polymorphonuclear leukocytes (PMNL). Therefore, we exposed PMNL to 2-EHA in vitro and measured the production of reactive oxygen species (ROS) and explored the associated cellular mechanisms. 2-EHA (10–2000 μM) inhibited dose-dependently formyl-methionyl-leucyl-phenylalanine (FMLP)-induced respiratory burst in PMNL. Moreover, 2-EHA decreased oxidative burst evoked by the protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and dioctanoyl-s,n-glycerol (DIC
8). 2-EHA affected neither the levels of free intracellular calcium nor inhibited PKC. The results indicate that 2-EHA inhibits activation of PMNL to produce ROS, i.e. has an immunosuppressive effect in vitro. The site of action in the PKC is after activation of this enzyme.