Thorium-induced oxidative stress mediated toxicity in mice and its abrogation by diethylenetriamine pentaacetate.
OBJECTIVE
Thorium ((232)Th, IV) preferentially accumulates in the liver, femur and spleen, which necessitates evaluation of its toxic effect in these organs. The present study was aimed at evaluation of liver function, oxidative stress and histological alterations in these organs.


METHODS
Swiss albino mice were administered either with Thorium nitrate (10 mg/kg body weight/day equivalent to 1,090 pCi/kg body weight/day) for 30 days (1/40th dose of LD(50/30); the dose of thorium required to kill 50% of the test cohort within 30 days) intraperitoneally or with calcium salt of diethylenetriamine pentaacetate (Ca-DTPA, 100 micromole/kg body/weight) intravenously or both. Liver function tests and oxidative damage was assessed. The concentration of Th in the tissues was determined by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method.


RESULTS
Administration of Th prevented the increase in the body and liver weight and altered liver functions. Th treatment to mice showed a decrease in the activities and gene expression of antioxidant enzymes, and increased lipid peroxidation and protein carbonylation. The extent of observed oxidative damage was correlated with accumulation of Th in examined organs and further associated with histological alterations. Furthermore it was found that these effects were significantly lower when the chelating agent, Ca-DTPA, was given 1 h after Th injection.


CONCLUSIONS
Administration of subtoxic concentration of Th to mice markedly altered the liver functions and induced oxidative stress in the liver, femur and spleen of mice. The results further demonstrated that Ca-DTPA significantly protected mice against the toxic effects of Th.
Kumar
Amit
A
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
Mishra
Pravin
P
Ghosh
Somnath
S
Sharma
Pragya
P
Ali
Manjoor
M
Pandey
B N
BN
Mishra
Kaushala Prasad
KP
D000818:Animals; D005260:Female; D007502:Iron Chelating Agents / Q000008:administration & dosage; D008107:Liver Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D018384:Oxidative Stress / Q000528:radiation effects*; D004369:Pentetic Acid / Q000008:administration & dosage*; D011832:Radiation Injuries / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000528:radiation effects*; D013910:Thorium / Q000633:toxicity*
D007502:Iron Chelating Agents; D013910:Thorium; D004369:Pentetic Acid