To assess the oxidative injuries caused by arsenic toxicity in rabbits and evaluate the detoxifying effects of exogenous antioxidants, we administered arsenic trioxide (3-5 mg/kg/day) in rabbits through a feeding tube for seven days. These rabbits were then treated with a recipe of vitamins, zinc, selenium (VZS) or a plant polyphenol or a placebo for the next seven days. Blood samples were collected from ear vein for spectrophotometric assay of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and nitrite/nitrate (NOx; index of nitric oxide formation) before arsenic administration, seven days after arsenic administration, and seven days after antioxidant treatment. The total arsenic concentrations in hair and spot urine samples of rabbits before arsenic administration were 0.6 ± 0.21 μg/g and 34.0 ± 5.9 μg/L, respectively. Administration of arsenic trioxide significantly increased arsenic concentrations in hair and in urine to 2.8 ± 0.40 μg/g (p < 0.001) and 7372 ± 1392.0 μg/L (p < 0.001), respectively. Arsenic administration to rabbits significantly reduced GSH concentration (post-arsenic, 17.5 ± 0.81 mg/dL vs. pre-arsenic, 32.0 ± 0.76 mg/dL, p < 0,001), increased TBARS concentration (post-arsenic, 8 ± 1.1 μM vs. pre-arsenic, 5 ± 0.7 μM, p < 0.05), and NOx concentration (post-arsenic, 465 ± 38.5 μM vs. pre-arsenic, 320 ± 24.7 μM, p < 0.001) as compared to the pre-arsenic levels. There was a negative correlation between TBARS and GSH concentrations (r = -0.464, p < 0.01) and between NOx and GSH concentrations (r = -0.381, p < 0.05) of intoxicated rabbits. The recovery of the depleted GSH was significantly greater in the polyphenols (77.0 ± 12.0%) or VZS (67.0 ± 17.0%) treatment groups compared with the placebo group (36.0 ± 7.0%). The decrease in NOx level of arsenic-treated rabbits was significantly greater in polyphenols treatment group than the placebo group (60.0 ± 9.0% vs. 17.0 ± 6.0%, p < 0.001). These results indicate that arsenic induces toxicity in rabbits associated with an increase in lipid peroxidation. Arsenic toxicity increases nitric oxide production in the body. Exogenous antioxidants such as polyphenols and recipe of vitamins, zinc, and selenium are useful for arsenic detoxification.
|Original language||English (US)|
|Number of pages||15|
|Journal||Journal of Environmental Science and Health - Part A Toxic/Hazardous Substances and Environmental Engineering|
|State||Published - 2003|
Bibliographical noteFunding Information:
This study was supported by ICDDR,B: Centre for Health and Population Research, Dhaka, Bangladesh, Ministry of Science and Technology, Government of Bangladesh, and UNICEF, Dhaka, Bangladesh. We thank Renata Pharmaceuticals for donating the study drugs.
Copyright 2008 Elsevier B.V., All rights reserved.
- Nitric oxide
- Rabbit model