Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 190, Issue 2, Pages 102-110Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0041-008X(03)00158-3
Keywords
organic solvents; neutrophils; oxidative stress; reactive oxygen species; MAPK pathway; ERK1/2
Categories
Ask authors/readers for more resources
In the present study we have examined the effects of hydrocarbons on the formation of reactive oxygen species (ROS) in human neutrophil granulocytes in vitro. We found that hydrocarbons induce ROS formation in a concentration-dependent manner and that the ROS-inducing potency increases with increasing number of carbon atoms in the structure. In general, aromatic hydrocarbons were less potent inducers of ROS than aliphatic and cyclic hydrocarbons. The most potent compound in each group, t-butylcyclohexane, n-decane, and n-butylbenzene, were chosen for mechanistic studies. ROS formation was inhibited by the MEK1/2 inhibitor U0126, the tyrosine kinase inhibitor erbstatin-A, and the phosphatidylinositol-3 kinase inhibitor wortmannin. The involvement of the ERK1/2 pathway was confirmed by Western blot analysis of phosphorylated ERK1/2. The study revealed only small differences in the mechanisms involved for the three compounds. The responses were not affected by Pertussis toxin, indicating that G(i)-protein coupled receptors are not involved in neutrophil activation after hydrocarbon exposure. Based on these findings we propose a mechanism involving tyrosine kinases, PI3 kinase, and the ERK1/2 pathway, leading to activation of the NADPH oxidase and production of ROS in neutrophils stimulated by organic solvents. (C) 2003 Elsevier Science (USA). All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available