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

Abstract

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.