Chemoprotective effects of captopril against cyclophosphamide-induced genotoxicity in mouse bone marrow cells.
The protective effects of captopril (CAP) against toxicity induced by cyclophosphamide (CP) in mice were investigated using the micronucleus assay for anticlastogenic activity in mouse bone marrow cells and liver glutathione (GSH) content. A single intraperitoneal (i.p.) injection of CAP at 50, 100, and 200 mg/kg 1 h prior to cyclophosphamide (50 mg/kg) reduced the frequency of micronucleated polychromatic erythrocytes (MnPCEs). All three doses of CAP significantly reduced the frequency of MnPCEs in mouse bone marrow compared to the group treated with CP alone (P<0.0001-0.01). CP significantly depleted the GSH content in liver but the application of CAP at a dose of 100 mg/kg 1 h before CP treatment repleted the GSH content. CAP 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. It appears that CAP, due to its antioxidant activity and by increasing GSH levels, can modulate the reduced cellular thiol content induced by CP and reduce the genotoxicity of CP in bone marrow cells.
Hosseinimehr
S J
SJ
Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. sjhosseinim@yahoo.com
Karami
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016587:Antimutagenic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D002216:Captopril / Q000627:therapeutic use*; D018890:Chemoprevention; D003520:Cyclophosphamide / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004900:Erythroblasts / Q000187:drug effects / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016587:Antimutagenic Agents; D000975:Antioxidants; D009153:Mutagens; D003520:Cyclophosphamide; D002216:Captopril; D005978:Glutathione