Protection effect of taurine on nitrosative stress in the mice brain with chronic exposure to arsenic

Abstract

Background: Arsenic exposure induces overproduction of reactive nitrogen species (RNS) in brain tissue and results in nucleic acid damage to the nerve cells. The 8-nitroguanine is one of the major products formed by the reaction of guanine, and ONOO-, and has been used as a popular biomarker of nucleic acid damage due to RNS attacking. In the present study, we examined whether the administration of taurine can protect against nucleic acid damage of brain neurons by arsenic-induced RNS.

Materials and methods: Sixty mice (30 male and 30 female) weighing 19.5 +/- 1.5 g were divided into 3 groups: (1) control group, (2) experimental group that received arsenic (As2O3), and (3) antagonistic group that received taurine with arsenic. Arsenic was administered for 60 days. 8-Nitroguanine expressions in brain neurons of mice were examined by the immunohistochemical method. Histopathological changes in brain tissues of mice were observed under light microscope and the immunohistochemistry method was used to investigate 8-nitroguanine expressions in cerebrum and cerebellum of mice.

Results: In the control group, no abnormal histopathological changes were observed in brain tissue of the mice. In brain tissue of the mice exposed to arsenic, histopathological results showed swells, evident vacuolar degeneration in cytoplasm, karyorrhexis and karyolysis. Relatively light pathological changes were observed in brain of the mice co-administered arsenic and taurine. Little or no expression of 8-nitroguanine in brain tissue was observed in controls. However, intensive expression of 8-nitroguanine was found in brain tissue of mice exposed to arsenic and it was mainly distributed in nucleus neighbouring the nuclear membrane, but a little in cytoplasm. A weak expression of 8-nitroguanine was observed in brain cells of mice co-administered arsenic and taurine.

Conclusions: The brain neurons may be the major target cells of arsenic neurotoxicity. Co-administration of arsenic and taurine can alleviate DNA damage of brain neurons caused by arsenic through the RNS signal pathway.

Figure 1

Histopathological changes in brain tissue of mice from each group. Pathological findings in the neuron of mice exposed to arsenic are observed. Axonal lose, cell shrinkage, evident vacuolar degeneration in cytoplasm and nucleus, karyorrhexis, and karyolysis are apparent. Relatively slight pathological changes are observed in cells from mice administered both arsenic and taurine. No abnormal histological changes in the brain tissues are observed in the control group. Bar = 50 µm.

Figure 2

8-Nitroguanine immunoreactivity in the neuron of cerebrum and cerebellum of mice from each group. Little or no expression of 8-nitroguanine in brain tissue was observed in control group. Intensive expression of 8-nitroguanine was found in neuron cells in the cerebral cortex exposed to arsenic. Significantly elevated 8-nitroguanine immunoreactivity is observed in the granular cells of cerebellum of mice exposed to arsenic; 8-nitroguanine expression was primarily distributed in the nucleus. The density and number of 8-nitroguanine immunopositive cells were decreased in the cerebellum of mice administered both arsenic and taurine. Little or no 8-nitroguanine expression was observed in the cerebellum of control group. Bar: Cerebrum = 100 µm. Cerebellum = 200 µm.

Figure 3

Effect of taurine on the formation of 8-nitroguanine in the cerebral cortex of mice brain exposed to arsenic. 8-Nitroguanine immunopositive cells in the cortex of mice brain in the control, arsenic and arsenic/taurine. Each microscopic scoring damage value represents the mean ± S.E.M of 10 microscopic fields in each animal. *P < 0.01 compared with the control group, and ^##P < 0.01 compared with the arsenic+taurine group.