Effect of sub-acute arsenic exposure on cerebral oxidative stress and Fos/Jun expression in rats

  Objective  To investigate the effect and mechanism of sub-acute arsenic exposure on cerebral oxidative stress in rats.

  Methods  Fifty-six Sprague-Dawley (SD) rats of clean grade were randomly divided into 4 groups (7 males and 7 females in each group): a control group, low-, moderate-, and high-dose groups (administered with drinking water containing 2.0, 10, and 50 mg/L sodium arsenite NaAsO₂ for 30 consecutive days). Arsenic content in brain tissues and blood were detected with inductively coupled plasma atomic emission spectrometry (ICP-AES); the level of reduced glutathione (GSH) in brain tissues was determined with 5, 5′-dithiobis-2-nitrobenzoic acid (DTNB) method; the activity of gamma-glutamylcysteine (γ-GCS) in brain tissues was measured with microdetermination of phosphorus; and c-fos and c-jun expressions in brain tissues were determined with immunohistochemical method.

  Results  Compared with those of the control group, the arsenic contents in blood and brain tissues were significantly higher in arsenic exposed groups (both P < 0.05); the rate of swelling, denaturation, and necrosis of neurons in brains of arsenic exposed groups were all higher than those of the control group. In brain tissues of the rats exposed to low-, moderate-, and high-dose arsenic, significantly decreased activity of γ-GCS (4.79 ± 0.60, 3.71 ± 0.87, and 3.13 ± 0.43 U/mgpro) and GSH level (29.59 ± 1.73, 24.57 ± 1.53, and 20.59 ± 2.51 μmol/gpro) were observed in comparison with those of the control rats (P < 0.05 for all); whereas, both the c-fos expression in hippocampus (65.36 ± 6.38%, 71.51 ± 6.05%, and 72.20 ± 6.13%) and in cortex (67.81 ± 7.47%, 70.99 ± 6.67, and 70.77 ± 4.79 %) and c-jun expression in hippocampus (56.67 ± 8.29%, 65.65 ± 5.70%, and 69.88 ± 2.85%) and in cortex (59.46 ± 6.05%, 65.80 ± 4.31%, and 67.51 ± 3.84%) increased significantly for the rats exposed to low-, moderate-, and high-dose arsenic compared to the control rats (P < 0.05 for all).

  Conclusion  In rats, sub-acute arsenic exposure results in overexpressions of c-fos and c-jun protein and downregulations of gamma-GCS activity and GSH level in brain tissues, which may attenuate cerebral capacity of against oxidative stress and may partially explain the mechanisms of central neurotoxicity induced by subacute arsenic exposure.