Captopril protects mice bone marrow cells against genotoxicity induced by gamma irradiation.
The radioprotective effects of captopril were investigated by using the micronucleus test for anticlastogenic and cell proliferation activity. A single intraperitoneal administration of captopril at doses of 10, 25 and 50 mg/kg 1 h prior to gamma irradiation (2 Gy) reduced the frequencies of micronuleated polychromatic erythrocytes (MnPCEs). All three doses of captopril significantly reduced the frequencies of MnPCEs and increased polychromatic erythrocytes (PCE)/PCE+NCE (normochromatic erythrocyte) ratio in mice bone marrow compared to the non-drug-treated irradiated control (p < 0.001). The optimum dose for protection in mouse was 10 mg/kg to protect mice bone marrow 2.18-fold against the clastogenic effects of gamma-irradiation with respect to the non-drug-treated irradiated control. There was a drug dose-response effect of captopril in increasing the PCE/PCE+NCE ratio in bone marrow cells. The maximum protective effect of captopril was at a dose of 25 mg/kg for increasing the PCE/PCE + NCE ratio. Captopril exhibited concentration-dependent antioxidant activity, scavenging > 96% of the 1,1-diphenyl-2-picryl hydrazyl free radicals when used at a concentration of 0.2 mM. In this study captopril reduced lipid peroxidation induced by hydrogen peroxide in mice liver. It appears that captopril, due to its free radical scavenging properties, protects mice bone marrow cells from radiation-induced DNA damage and genotoxicity.
Hosseinimehr
Seyed Jalal
SJ
Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. sjhosseinim@yahoo.com
Mahmoudzadeh
Aziz
A
Akhlagpour
Shahram
S
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000528:radiation effects*; D002216:Captopril / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005720:Gamma Rays; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D015162:Micronucleus Tests; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D008315:Malondialdehyde; D002216:Captopril