Contribution of Glutathione and Metallothionein to Acute Toxicity of Cadmium

摘要

Cadmium (Cd) is a harmful heavy metal widely present in the environment. Liver and kidney are the target tissues of acute and chronic Cd exposure, respectively. Glutathione (GSH) and metallothionein (MT)-I/II are known as defensive factors against Cd, but no studies have been conducted to compare them at the same time. In this study, to clarify the contribution of GSH and MT-I/II to acute toxicity of Cd, we examined using GSH-depleted mice and MT-I/II null mice. GSH-depleted mice were prepared by subcutaneously administering L-Buthionine-sulfoximine after 20 h of fasting to 10-week-old female C57BL/6J wild-type mice. GSH-depleted mice, MT-I/II null mice, and wild-type mice were subcutaneously treated with 17.5 μmol Cd/kg. Twenty-four hours later, GOT and GPT activities, and urea nitrogen (BUN) and creatinine (Cre) levels in the serum were measured as an indicator of hepatotoxicity and nephrotoxicity. Cd did not induced hepatotoxicity and nephrotoxicity in wild-type mice. On the other hand, GOT and GPT activities, and BUN and Cre levels in GSH-depleted mice and MT-I/II null mice were significantly increased by Cd. Both hepatotoxicity and nephrotoxicity in GSH-depleted mice treated with Cd were stronger than those in MT-I/II null mice. All of GSH-depleted MT-I/II null mice died by Cd. These results suggested that GSH plays an important role as a biological protective factor against acute toxicity of Cd compared with MT-I/II.