Environmental enrichment restores oxidative balance in animals chronically exposed to toluene: Comparison with melatonin

Abstract Inhalants are widely used as recreational drugs, and toluene is the main chemical compound present in most inhalants used for these purposes. Previous studies have shown that repeated toluene exposure produces cellular death and memory impairment, while environmental enrichment (EE) rescues from those effects. However, the mechanisms involved in those responses are unclear. Previous studies have shown that toluene induces a redox imbalance at the neuronal level; although, details on the mechanism of action of environmental enrichment enhancing antioxidant capacity remain to be explored. It is also unexplored whether this putative antioxidant capacity is similar to that produced by pharmacological antioxidants. To study this hypothesis, Swiss-Webster male mice were chronically exposed to toluene (0 or 4000 ppm, 30 min/day/4 weeks). Subsequently, neurochemical tests were conducted to measure biomarkers of oxidative stress (ROS, NO, GSH/GSSG ratio and SOD activity) in the hippocampus and the prefrontal cortex. In the second part of the study, we evaluated the putative antioxidant capacity of environmental enrichment and compared it to that of melatonin, a known free radical scavenger and inductor of antioxidant defences. The results showed that chronic toluene exposure increased the levels of pro-oxidative molecules and decreased the antioxidant markers. Conversely, environmental enrichment restored oxidative balance in animals previously exposed to toluene. Furthermore, the effects of EE were similar to those obtained with melatonin. Altogether, alterations in oxidative balance could represent an intermediate signalling pathway in the cascade of effects induced by toluene, while EE and melatonin appear to have the ability to rescue those effects.