BACKGROUND: Oxidative stress has been implicated in the initiation of hepatic damage caused by various agents. Not much data on oxidative stress in liver in chronic arsenic exposure are available in the literature. We therefore studied this aspect in a murine model. METHODS: BALB/c mice were given arsenic-contaminated (3.2 mg/L) or arsenic-free (< 0.01 mg/L, control) drinking water ad libitum. Batches of mice were sacrificed after 2 and 4 months, and blood samples and liver tissue were collected. Liver histology was examined and levels of hepatic reduced glutathione (GSH), malondialdehyde, and enzymes of the antioxidant defense system in the liver tissue were determined. Arsenic content in liver tissues obtained at 4 months was estimated. RESULTS: Two-month exposure to arsenic caused significant elevation of hepatic GSH (11.4 [0.8] micrograms/mg protein) compared to control mice (9.3 [0.4]; p < 0.01). Levels of enzymes related to GSH homeostasis were also elevated. At 4 months, hepatic GSH was significantly reduced (8.4 [0.5] micrograms/mg protein) when compared to control mice (9.3 [0.4]; p < 0.01). Arsenic content in the liver tissue after 4 months of exposure was significantly higher (0.40 [0.05] microgram/g) as compared to control mice (0.04 [0.04]; p < 0.01). CONCLUSION: The results suggest that the antioxidant defense system in the liver of mice is activated after exposure to arsenic for 2 months. However, prolonged exposure to arsenic probably causes overuse failure of this system, which might result in initiation of biochemical injury to the liver.
BACKGROUND: Oxidative stress has been implicated in the initiation of hepatic damage caused by various agents. Not much data on oxidative stress in liver in chronic arsenic exposure are available in the literature. We therefore studied this aspect in a murine model. METHODS: BALB/c mice were given arsenic-contaminated (3.2 mg/L) or arsenic-free (< 0.01 mg/L, control) drinking water ad libitum. Batches of mice were sacrificed after 2 and 4 months, and blood samples and liver tissue were collected. Liver histology was examined and levels of hepatic reduced glutathione (GSH), malondialdehyde, and enzymes of the antioxidant defense system in the liver tissue were determined. Arsenic content in liver tissues obtained at 4 months was estimated. RESULTS: Two-month exposure to arsenic caused significant elevation of hepatic GSH (11.4 [0.8] micrograms/mg protein) compared to control mice (9.3 [0.4]; p < 0.01). Levels of enzymes related to GSH homeostasis were also elevated. At 4 months, hepatic GSH was significantly reduced (8.4 [0.5] micrograms/mg protein) when compared to control mice (9.3 [0.4]; p < 0.01). Arsenic content in the liver tissue after 4 months of exposure was significantly higher (0.40 [0.05] microgram/g) as compared to control mice (0.04 [0.04]; p < 0.01). CONCLUSION: The results suggest that the antioxidant defense system in the liver of mice is activated after exposure to arsenic for 2 months. However, prolonged exposure to arsenic probably causes overuse failure of this system, which might result in initiation of biochemical injury to the liver.
Authors: Xiang Zhang; Walter H Watson; Xue Shi; Xiaoli Wei; Imhoi Koo; Robin H Schmidt; Xinmin Yin; Seong Ho Kim; Andrew Vaughn; Craig J McClain; Gavin E Arteel Journal: J Proteome Res Date: 2013-12-17 Impact factor: 4.466