Ebselen attenuates cyclophosphamide-induced oxidative stress and DNA damage in mice.
The role of selenium, a trace element in the human diet, has been extensively studied against cancer, immunity and infectious/inflammatory diseases. The purpose of the present study was to investigate the beneficial effect of ebselen, an organo-selenium compound, against cyclophosphamide-induced oxidative stress and DNA damage in mice. Malondialdehyde and total glutathione were estimated in the liver to detect the oxidative stress induced by cyclophosphamide. Standard and modified comet assays (the latter incorporated lesion-specific enzymes, formamidopyrimidine-DNA glycosylase and endonuclease-III) were used to detect the normal and oxidative stress-induced DNA damage by cyclophosphamide in the mouse bone marrow and the peripheral blood lymphocytes. In addition, a micronucleus assay capable of detecting DNA damage was also carried out in the mouse bone marrow and the peripheral blood reticulocytes induced by cyclophosphamide. The results confirm that pre-treatment with ebselen (2.5, 5 and 10 mg/kg) for 5 consecutive days decreased the oxidative stress induced by cyclophosphamide (100 mg/kg) based on the restoration in concentration of malondialdehyde and glutathione in the liver and decreased DNA damage and micronuclei count in the bone marrow and the peripheral blood. It is concluded that pre-treatment with ebselen attenuates cyclophosphamide-induced oxidative stress and the resultant DNA damage in mice.
Tripathi
D N
DN
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Punjab-160062, India.
Jena
G B
GB
D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D054833:Isoindoles; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*
D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D003520:Cyclophosphamide; D005978:Glutathione