Toxicity and Oxidative Stress Induced by Organic Arsenical Diphenylarsinic Acid and Inorganic Arsenicals and Their Effects on Spatial Learning Ability in Mice

Abstract

In the present study, we investigated the oxidative stress induced by arsenical compounds in mice. Catalase (CAT) activity in the liver was decreased significantly when an organic arsenical compound, diphenylarsinic acid (DPAA), was administered to mice for 7 and 28 consecutive days. Reduced glutathione (GSH) was decreased significantly in the blood of the mice treated for 7 days with another organic arsenical, phenylmethyl arsonic acid (PMAA), and an inorganic arsenical, Na₂HAsO₄, as well as DPAA. GSH was also decreased significantly in the brain of the mice treated for 28 days with DPAA. Arsenic concentrations in the brain of the mice administered DPAA for 7 or 28 days were 1.6-3.0 times higher than those in the livers of these mice. The levels were about 3.0-14 times higher than those in the brains of mice administered inorganic arsenicals, suggesting that organic arsenicals tended to be more highly accumulated in the brain than inorganic arsenicals. The Morris water maze test supported these results, i.e., the latency time of the mice administered DPAA was significantly longer than that of the mice administered Na₂HAsO₄ or NaAsO₂, as well as that of controls without arsenical. These results showed that DPAA decreased GSH in the blood, liver and brain, and that DPAA was more easily transferred to the brain. It was suggested that spatial learning ability was depressed by the accumulation of DPAA in the brain.