Spironolactone improves nephropathy by enhancing glucose-6-phosphate dehydrogenase activity and reducing oxidative stress in diabetic hypertensive rat

Autor(es)

Pessoa, Bruno S. ^[1] ; Peixoto, Elisa B. M. I. ^[1] ; Papadimitriou, Alexandros ^[1] ; Lopes de Faria, Jacqueline M. ^[1] ; Lopes de Faria, Jose B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Fac Med Sci, Renal Pathophysiol Lab, Dept Internal Med, BR-13083887 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM; v. 13, n. 1, p. 56-66, MAR 2012.
• Citações Web of Science: 16

Resumo

Spironolactone (SPR), a mineralocorticoid receptor blocker, diminishes hyperglycemia-induced reduction in glucose-6-phosphate dehydrogenase (G6PD) activity, improving oxidative stress damage. This study investigated whether SPR ameliorates nephropathy by increasing G6PD activity and reducing oxidative stress in spontaneously hypertensive diabetic rats (SHRs). The streptozotocin-induced diabetic rats received or not SPR 50 mg/kg per day, for eight weeks. A human mesangial cell line was cultured in normal or high glucose conditions, with or without SPR, for 24 h. Plasma glucose levels and systolic blood pressure were unaltered by diabetes or by SPR treatment. Albuminuria, fibronectin expression, 8-OHdG urinary levels, lipid peroxidation and p47phox expression were higher in the diabetic rats compared with the control and were reduced by SPR. The antioxidant GSH/GSSG ratio was reduced in the diabetic rats and the treatment reestablished it. Diabetes-induced SGK1 up-regulation was inhibited by SPR. Reactive oxygen species (ROS) and superoxide production induced by NADPH oxidase were increased by hyperglycemia and high glucose, in vivo and in vitro, respectively, and were reduced with SPR. Hyperglycemia and high glucose decreased G6PD activity, which was restored with SPR. These results suggest that SPR ameliorates nephropathy in diabetic SHRs by restoring G6PD activity and diminishes oxidative stress without affecting glycaemia and blood pressure. (AU)

• Processo FAPESP: 08/52575-9 - Qual o mecanismo primario responsavel pela melhora da nefropatia diabetica experimental com o emprego da espironolactona: reducao da inflamacao ou do estresse oxidativo?
• Beneficiário: Bruno Sevá Pessôa
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/57560-0 - Efeitos do chá verde (Camellia sinensis), do cacau e de um doador de óxido nítrico na nefropatia e retinopatia diabética: papel da redução do estresse oxidativo e da inflamação e do aumento do óxido nítrico
• Beneficiário: Jose Butori Lopes de Faria
• Modalidade de apoio: Auxílio à Pesquisa - Temático