Effect Of Toluene Exposure Research Articles

Effect of toluene exposure on the antioxidant status and apoptotic pathway in organs of the rat

The chronic abuse of the solvent toluene results in structural and functional impairment of various organs. However, the pathophysiological mechanisms that cause these impairments of function are not clearly understood. This study aims to assess the effect of chronic toluene exposure (15, 30 and 45 days) on the oxidative stress and antioxidant status of different organs in the rat. Also, cyclooxygenase-2 and caspase-3 activities (a marker of apoptosis) are studied. Forty male albino rats were used and divided into four groups: controls (group I) and three other groups receiving a single daily dose of toluene (650 mg/kg) for 15 days (group II), 30 days (group III) and 45 days (group IV). The animals were then sacrificed and the brain cortex, cerebellum, liver, kidney and testis were separated for the determination of thiobarbituric acid reactive substance (TBARS), GSH, glutathione disulphide (GSSG) and glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), cyclooxygenase-2 (COX-2) and caspase-3 activity. Results showed a significant and time-dependent increase in the levels of TBARS, GSSG and in GST, SOD, COX-2 and caspase-3 activity, while GSH, GR and GPx showed a marked decline in most tissues. The brain (cortex and cerebellum) was the most affected organ, showing the greatest increase in one apoptotic marker (caspase-3), while the testis and kidneys were least affected. In conclusion, oxidative stress and derangement of the GSH:GSSG ratio, induced chronic inflammatory change and apoptosis may play an essential role in toluene toxicity.

Enhancement of glial cell line-derived neurotrophic factor expression in rat adrenal glands by toluene exposure.

Toluene, a widely used industrial organic solvent, has been shown to influence the function of catecholaminergic cells including sympathoadrenergic neurons and adrenal medullary cells. While glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta superfamily, has recently been shown to be expressed in rat adrenal glands, and suggested as playing a potential autocrine or paracrine role in development and differentiation of the adrenal medullary cell. Based on these findings, it seemed of interest to examine the effect of toluene exposure on GDNF expression in the adrenal medulla. Toluene inhalation (1500 ppm for 4h on 4-10 days) increased GDNF protein content in rat adrenal glands without any significant change in GDNF mRNA level. Furthermore, toluene exposure failed to cause any notable change in the expression of mRNA encoding phenylethanolamine N-methyltransferase (PNMT), a stress-inducible enzyme in the adrenal medulla. These results suggest that the elevation of GDNF protein expression caused by toluene exposure is likely due to the enhancement of protein synthesis and/or processing rather than the stimulation of GDNF gene transcription in rat adrenal glands, and may not be directly associated with the stress response of adrenal glands during toluene inhalation.

Effect of toluene inhalation on extracellular striatal acetylcholine release studied with microdialysis.

Intracerebral microdialysis was performed on awake, freely moving rats in order to record effect of toluene exposure on acetylcholine release in striatum. Acetylcholine release decreased during (about 20%) and after (about 60%) toluene exposure (2 hr, 2000 p.p.m.) Striatal acetylcholine release is thought to be mediated by dopamine. In a previous work we found that extracellular dopamine levels increase during toluene exposure. A dopamine uptake inhibitor (LU 19-005, 2 mg/kg) was therefore injected subcutaneously and the effect of increased extracellular dopamine on acetylcholine release within the striatum was monitored in the absence of toluene exposure. LU 19-005 increased striatal dopamine levels six times and the acetylcholine levels increased to about 145% of basal value. The present study shows that toluene exposure decrease acetylcholine release while an injection of a dopamine uptake inhibitor fails to decrease acetylcholine release. Indicating that acute exposure of toluene decreases striatal acetylcholine release by a mechanism that is not mediated by increased extracellular dopamine levels. Our data suggest that toluene decrease acetylcholine release within the striatum and that this effect not is mediated by increased extracellular dopamine levels.

Human response to varying concentrations of toluene

Thirty two males and 39 females aged 31-50 were exposed for 7 h to one of the three following conditions: (1) Clean air, (2) constant exposure to 100 ppm toluene, or (3) a varying exposure with the same time-weighted average, but with peaks of 300 ppm every 30 min. During exposure the subjects exercised in three 15-min periods with a load of 50 to 100 W. Exposure to toluene caused significant (P less than 0.05) complaints about poor air quality, altered temperature and noise perception, increased irritation in the nose and the lower airways, feeling of intoxication, and there were tendencies (P less than 0.1) towards irritation in the throat, headache and dizziness. In the four performance tests there was a tendency towards a lower score in a vigilance test while no effect of toluene exposure was seen in a peg board test, a five choice serial reaction test, or a colour test, indicating only minimal if any effect on the psychomotor or visual performance. There was no difference in the acute effects caused by the exposure containing peak concentrations and by the constant exposure.

The Effect of Toluene Exposure for up to 18 Months (78 Weeks) on the (Ca2+/Mg2+)ATPase and Fluidity of Synaptosomal Membranes Isolated from Rat Brain

The effect of toluene on the central nerve system was studied by using rat brain synaptosomal membranes as in vitro and in vivo models. The activity of Ca2+/Mg2+ ATPase and the membrane fluidity were determined. Short-term exposure in vivo to 500 p.p.m. of toluene had an inhibitory effect on the enzyme studied whereas long-term exposure to toluene caused an increased activity. Exposure to toluene had no effect at all on the membrane fluidity. The in vitro experiment showed an effect of toluene on both parameters. The alteration in the enzyme activity and membrane fluidity was parallel in the exposed animals as well as those of control. Our results show that long-term exposure to toluene affects nerve cell membranes by other mechanisms than those observed under in vitro conditions.

Effect of toluene exposure on the liver under different experimental conditions

The effect of exposure to toluene inhalation was studied in adult mice, rats, and rabbits, and, further, in rats of different age groups and rats subjected to partial hepatectomy or ligation of the common bile duct. It was found that (1) toluene has no substantial liver damaging effect on the mouse, rat, or rabbit; (2) induction of microsomal monooxygenase enzymes by toluene is almost completely independent of physiological changes affecting the functional-anatomical state of the liver (aging), of restriction of the functional capacity of the organ (partial hepatectomy), and of irreversible hepatic damage (bile duct ligation); (3) toluene does not in any way interfere with surgically induced hepatic damage. The consequences of surgical interventions, in turn, just like the age-dependent changes, do not modify the minimal ultrastructural damaging effect of toluene.