Exposure to 1-bromopropane induces microglial changes and oxidative stress in the rat cerebellum

• Published in: Toxicology (Amsterdam) 2012-12, Vol.302 (1), p.18-24
• Main Authors: Subramanian, Kaviarasan, Mohideen, Sahabudeen Sheik, Suzumura, Akio, Asai, Naoya, Murakumo, Yoshiki, Takahashi, Masahide, Jin, Shijie, Zhang, Lingyi, Huang, Zhenlie, Ichihara, Sahoko, Kitoh, Junzoh, Ichihara, Gaku
• Format: Article
• Language: English
• Subjects: 1-Bromopropane; Animals; Biological and medical sciences; Central nervous system; Cerebellum; Cerebellum - drug effects; Cerebellum - pathology; Dose-Response Relationship, Drug; Emergency; humans; Hydrocarbons, Brominated - administration & dosage; Hydrocarbons, Brominated - toxicity; immunohistochemistry; Male; Markers; Medical sciences; Microglia; Microglia - drug effects; Microglia - metabolism; neuroglia; Neurotoxicity; nitric oxide; Nitric Oxide - metabolism; Oxidative stress; Oxidative Stress - drug effects; Protein Carbonylation - drug effects; Proteins; Rats; Rats, Wistar; reactive oxygen species; Reactive Oxygen Species - metabolism; reproductive toxicology; Solvents; Solvents - administration & dosage; Solvents - toxicity; Stresses; Thiobarbituric Acid Reactive Substances - metabolism; thiobarbituric acid-reactive substances; Toxicity; Toxicology
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2012.07.006

1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, is reported to exhibit neurotoxicity and reproductive toxicity in animals and humans. However, the underlying mechanism of the toxicity remains elusive. This study was designed to identify the microglial changes and oxidative stress in the central nervous system (CNS) after 1-BP exposure. Four groups of Wistar-ST rats (n=12 each) were exposed to 0, 400, 800 and 1000ppm of 1-BP, 8h/day for 28 consecutive days. The cerebellum was dissected out in 9 rats of each group and subjected to biochemical analysis, while the brains of the remaining 3 rats were examined immunohistochemically. Exposure to 1-BP increased the levels of oxidative stress markers [thiobarbituric acid reactive substances (TBARS), protein carbonyl and reactive oxygen species (ROS)] in a dose-dependent manner. Likewise, there was also 1-BP dose-dependent increase in nitric oxide (NO) and dose-dependent decrease in protein concentrations in the cerebellum. Immunohistochemical studies showed 1-BP-induced increase in cd11b/c-positive microglia area in the white matter of the cerebellar hemispheres. The results showed that exposure to 1-BP induced morphological change in the microglia and oxidative stress, suggesting that these effects are part of the underlying neurotoxic mechanism of 1-BP in the CNS.