Ebselen Protects Against Oxidative and Morphological Effects of High Concentration Chronic Toluene Exposure on Rat Sciatic Nerves

Abstract

Aim: Neuroprotective effects of ebselen against free radical damage have been studied extensively. Toluene generates reactive oxygen species (ROS) and the toxic effects relating to these reactants. The aim of this study was designed to investigate the effects of chronic toluene inhalation in high concentration on lipid peroxidation, antioxidant enzyme activities and ultrastructural changes in the sciatic nerves of rats.Methods: We also examined the protective effects of ebselen against toluen exposure. Male Wistar albino rats (150-250 g) were divided in three experimental groups: the control, toluene and toluene+ebselen treated group (n=10 for each). Toluene treatment was performed by inhalation of 3000 ppm toluene, in a 8 hr/day and 6 day/week order for 16 weeks. Control group received 1ml serum physiologic and ebselen was given i.p. (10 mg/kg) to toluene+ebselen treated group just after toluene exposure per day. Blood and tissue samples were obtained for biochemical and histopathological investigation. The blood and sciatic nerves were assayed for toluene by gas chromatography.Results: Toluene significantly increased blood and tissue malondialdehyde (MDA), and decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but not tissue catalase (CAT) levels when compared with controls. Ebselen administration prevented to increase of blood and tissue MDA and decrease to SOD and GSH-Px levels induced by toluene inhalation. Electron micrographs of sciatic nerve in the toluene group shows myelin destructions with onion-bulb and bubble form protrusion on the myelin sheath and axolemma border of myelinated axons. Furthermore, ebselen salvaged the nerve fibers from toluene exposure.Conclusion: Ebselen treatment may provide neuroprotection against toluene neurotoxicity by directly scavenging ROS and by indirectly augmenting their antioxidant capacity.

Protective effects of thymoquinone on the neuronal injury in frontal cortex after chronic toluene exposure

“…In the present study, chronic toluene exposure caused severe degenerative changes, shrunken cytoplasma, slightly dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the frontal cortex. These findings are in agreement with the results of other investigators on toluene -induced neurotoxicity in different animals (Altenkirch et al 1977;Coskun et al 2006;Saavedra et al 1996;Korbo et al 1996).…”

“…Coskun et al (2006) suggested that increased lipid peroxidation, reduced antioxidant enzyme activities, and ultrastructural changes found in their study indicates that chronic toluene inhalation might be involved free radical processes. In the present study, chronic toluene exposure caused severe degenerative changes, shrunken cytoplasma, slightly dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the frontal cortex.…”

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats

“…However, the 30 mg/kg dose of ebselen did not significantly increase antioxidant enzyme activities. Our results were consistent with previous studies [21][22][23]30,31]. Therefore, we suggest that the protective effects of the 15 mg/kg dose of ebselen may be exerted via improvement of the antioxidant defense system in sciatic nerve I/R injury.…”

“…Moreover, the 30 mg/kg dose of ebselen significantly increased LPO accumulation compared with the sham group. The results of this study were consistent with previous studies [21][22][23]. Consequently, while the 15 mg/kg dose of ebselen pretreatment may be protective against sciatic nerve I/R injury by reducing LPO, the 30 mg/kg dose of ebselen appears to have little or no effect on LPO.…”

Protective Effects of Nigella sativa on the Neuronal Injury in Frontal Cortex and Brain Stem After Chronic Toluene Exposure

“…Pathological studies of the effects of toluene inhalation based on biopsies of the sural nerve have shown swelling of the axons and an extremely thin lamella of the myelin sheath [42]. Coskun et al [43] suggested that increased lipid peroxidation, reduced antioxidant enzyme activities, and ultrastructural changes found in their study indicates that chronic toluene inhalation might be involved free radical processes. In the present study, chronic toluene exposure caused severe degenerative changes, shrunken cytoplasma, slightly dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the frontal cortex and brain stem.…”