Vis sammendrag
As a consequence of interaction with a variety of stimuli, human
neutrophil granulocytes (a group of leukocytes) undergo a marked
increase in oxygen metabolism, termed the respiratory burst [1]. One
oxygen-centered free radical (superoxide) has been unequivocally shown
to result from this respiratory burst, and some experimental evidence
for another (hydroxyl) has been published. Neutrophils kill
microorganisms by ingesting them into phagocytic vacuoles and then
bombarding them with reactive oxygen species and contents of cellular
granules [2]. Whether organic solvents may lead to free-radical
generation and the damages from organic solvents (particularly to the
brain) are due to free radicals, have been subjects of discussion.
Organic solvents such as toluene and "white spirit" have been shown to
cause elevation of reactive oxygen species in mammal central nervous
system [3]. Little is known about solvent-induced mechanisms for
initiation of respiratory burst in human neutrophils. With background
in inhalation experiments on rats, three organic solvents were chosen
at relevant concentrations. Respiratory burst was assayed using EPR
spin trapping, and by a fluorescence technique. Mechanisms for organic
solvent-induced production of reactive oxygen species were elucidated
by the use of enzymatic inhibitors. We evaluated the use of the spin
trap DEPMPO for assessment of superoxide free radicals formed by human
neutrophil granulocytes, and found it suitable. Effects of the organic
solvents 1,2,4-trimethylcyclohexane, n-nonane and
1,2,4-trimethylbenzene on free-radical production in vitro in human
neutrophil granulocytes were examined. Low concentrations of two of
these organic solvents stimulated human neutrophil granulocytes to
produce superoxide free radicals. Mechanisms for the free-radical
production induced by 1,2,4-trimethylcyclohexane were elucidated by the
use of enzymatic inhibitors [4]. Both an NADPH-oxidase inhibitor and a
protein kinase C inhibitor blocked this production. Further, the free
radical production depended on extracellular calcium, phospholipase C
and phospholipase D.
[1] Baldridge, C.W. and Gerard, R.W. American journal of physiology
1933, 103, 235-236. [2] Kettle, A.J. and Winterbourn, C.C. Redox Report
1997, 3, 3-15. [3] Lam, H.R.; Ostergaard, G.; Guo, S.X.; Ladefoged, O.;
Bondy, S.C. Biochemical Pharmacology 1994, 47, 651-657. [4] Myhre, O.;
Vestad, T.A.; Sagstuen, E.; Aarnes, H.; Fonnum, F. Toxicology and
Applied Pharmacology, submitted.
