Free radical induction in the brain and liver by products of toluene catabolism

Abstract

Abstract-Toluene and its metabolites have been studied with respect to their reactive oxygen speciesenhancing potential in isolated systems and in vivo. The induction of reactive oxygen species (ROS) production was assayed using the probe 2' ,7' -dichlorodihydroftuorescin diacetate (DCFH-DA). Intraperitoneal injection of toluene, benzyl alcohol or benzaldehyde caused a significant elevation in the rate of ROS formation within hepatic mitochondrial fractions (P2). In the brain, only toluene induced ROS formation, while benzyl alcohol and benzaldehyde did not have any effect. Glutathione (GSH) levels were depressed in liver and brain regions from toluene-treated rats. However, no such depression was evident in brains treated with toluene metabolites. P2 fractions from phenobarbital-pretreated rats exhibited a heightened ROS response when challenged with toluene, in vitro. Pretreatment of rats in vivo with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, or sodium cyanamide, an aldehyde dehydrogenase inhibitor, prior to exposure to toluene, caused a significant decrease and increase, respectively, in toluene-stimulated rates of ROS generation in the CNS and liver. Electron spin resonance spectroscopy, employing the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was conducted. Incubation of the spin trap with P2 fractions and toluene or benzaldehyde elicited a spectrum corresponding to the hydroxyl radical. Incubation of benzaldehyde with aldehyde dehydrogenase produced a strong signal that was blocked completely by superoxide dismutase and inhibited partially by catalase, suggesting the presence of superoxide radicals and the involvement of the iron-catalyzed Haber-Weiss reaction leading to the production of hydroxyl radicals. Thus, ROS generation during toluene catabolism may occur at two steps: cytochrome P450 oxidation and aldehyde dehydrogenase oxidation. In addition, GSH may play an important role in protection against the induction of ROS generation in the CNS and liver following exposure to toluene.

Changes in markers of oxidative status in brain, liver and kidney of young and aged rats following exposure to aromatic white spirit

“…This is in contrast to our previous study of dearomatized white spirit (Lam et al 1994). It is also in contrast to our earlier findings of the induction of cerebral prooxidant events by acute intraperitoneal administration of a single aromatic solvent, toluene (Mattia et al 1993b). However such high-dose, short-term studies are very different from the prolonged low level exposure used here.…”

Three weeks' exposure of rats to dearomatized white spirit modifies indices of oxidative stress in brain, kidney, and liver

“…There is considerable evidence for the induction of excess free radicals and ROS* generation by various neurotoxic aromatic solvents. These compounds include benzene [16], toluene [17][18][19], xylenes [19][20][21], and styrene [22]. There is less evidence for the induction of oxidative stress by aliphatic organic solvents.…”

Acute cardiotoxic effects of high dose toluene: an experimental study

“…Toluene and its metabolites can cause damage in many tissues via the oxidative stress pathway (11,22). One such form of damage, apoptosis is a type of programmed cell death characterized by fragmentation of the DNA, shrinkage of the cytoplasm, membrane changes, and cell death without lysis or damage to neighboring cells (23). Toluene has been shown to increase apoptotic activity (24)(25)(26).…”