title: Antioxidants in detoxification of arsenic-induced oxidative injury in rabbits: preliminary results.
abstract: 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 microg/g and 34.0 +/- 5.9 microg/L, respectively. Administration of arsenic trioxide significantly increased arsenic concentrations in hair and in urine to 2.8 +/- 0.40 microg/g (p<0.001) and 7372 +/- 1392.0 microg/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 microM vs. pre-arsenic, 5 +/- 0.7 microM, p<0.05), and NOx concentration (post-arsenic, 465 +/- 38.5 microM vs. pre-arsenic, 320 +/- 24.7 microM, 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.
authors.affiliation: Physiology Laboratory, Clinical Sciences Division, ICDDR,B: Centre for Health and Population Research, Dhaka, Bangladesh. rabbani@icddrb.org
authors.forename: Golam Hassan
authors.initials: GH
authors.lastname: Rabbani
authors.forename: Shyamal Kumar
authors.initials: SK
authors.lastname: Saha
authors.forename: Mastura
authors.initials: M
authors.lastname: Akhtar
authors.forename: Farzana
authors.initials: F
authors.lastname: Marni
authors.forename: Amal Krishna
authors.initials: AK
authors.lastname: Mitra
authors.forename: Shamsir
authors.initials: S
authors.lastname: Ahmed
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alauddin
authors.forename: Maya
authors.initials: M
authors.lastname: Bhattacharjee
authors.forename: Shamima
authors.initials: S
authors.lastname: Sultana
authors.forename: A K Azad
authors.initials: AK
authors.lastname: Chowdhury
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001151:Arsenic / Q000652:urine; D020261:Arsenic Poisoning / Q000188:drug therapy* / Q000503:physiopathology*; D016166:Free Radical Scavengers / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D006197:Hair / Q000737:chemistry; D009569:Nitric Oxide / Q000032:analysis; D018384:Oxidative Stress; D011817:Rabbits
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D005978:Glutathione; D001151:Arsenic