title: Effect of captopril and the bradykinin-PKC pathway on ROS production in type 1 diabetic rats.
abstract: The aim of this study was to investigate the possible effects of captopril as a promoter in modulating the oxidant-antioxidant balance in rats with type 1 diabetes, and the influence of protein kinase C (PKC) pathways in the production of reactive oxygen species (ROS) induced by bradykinin in type 1 diabetic rats. This study evaluated the redox status in both the cardiac tissue and at the cellular level (neutrophils). Two concentrations of captopril were utilized: (i) 5 mg·(kg body mass)(-1), which was considered a therapeutic dose; and (ii) 10 mg·(kg body mass)(-1). Body mass, plasma glucose, and serum insulin were evaluated. To investigate the redox status of the cardiac tissue, we analyzed lipid peroxidation, concentration of carbonylated protein, catalase activity, and the concentration of glutathione. For a more accurate assessment of the possible antioxidant effect of captopril, we also analyzed ROS in neutrophils (in vivo), and ROS production induced by bradykinin and the influence of the PKC pathway in this production (in vitro). Our data show that the hearts of diabetic animals have increased oxidative damage, exemplified by the increased concentration of carbonylated protein and thiobarbituric acid reactive substances (TBARS). However, animals treated with captopril at both concentrations showed lower concentrations of carbonylated protein compared with untreated diabetic animals. We found an increase of catalase activity in the heart of diabetic rats, which was reversed by captopril treatment at both of the dosages tested. Our data showed that captopril was able to reduce ROS production in the neutrophils of diabetic rats at a dose of 10 mg captopril·(kg body mass)(-1). However, the antioxidant effect of captopril is independent of bradykinin. Diabetes induces oxidative stress, and these results suggest that captopril has an antioxidant effect and can modulate the production of ROS in circulating neutrophils.
authors: a Programa de Pós-graduação em Ciências Biológicas do Núcleo de Pesquisas em Ciências Biológicas - NUPEB, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, MG, 35400-000, Brazil.
authors: Glaucy
authors: G
authors: Rodrigues de Araujo
authors: Karine
authors: K
authors: Granato de Faria
authors: Wanderson Geraldo
authors: WG
authors: Lima
authors: Bruno da Cruz
authors: Bda C
authors: Pádua
authors: Joamyr Victor
authors: JV
authors: Rossoni
authors: Aline Arlindo
authors: AA
authors: Souza
authors: Deoclecio
authors: D
authors: Chianca-Júnior
authors: Marcelo Eustáquio
authors: ME
authors: Silva
authors: Maria Lucia
authors: ML
authors: Pedrosa
authors: Miriam Martins
authors: MM
authors: Chaves
authors: Daniela Caldeira
authors: DC
authors: Costa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000097:blood; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D017382:Reactive Oxygen Species; D002216:Captopril; D011493:Protein Kinase C; D001920:Bradykinin