RESUMEN

Preconditioning episodes of ischemia/reperfusion (IR) induce protection against acute kidney injury (AKI), however their long-term effect still unknown. We evaluated AKI to chronic kidney disease (CKD) transition, after three-mild or three-severe episodes of IR. AKI was induced by single bilateral IR (1IR), or three episodes of IR separated by 10-day intervals (3IR) of mild (20 min) or severe (45 min) ischemia. Sham-operated rats served as controls. During 9-months, the 1IR group (20 or 45 min) developed CKD evidenced by progressive proteinuria and renal fibrosis. In contrast, the long-term adverse effects of AKI were markedly ameliorated in the 3IR group. The acute response in 3IR, contrasted with the 1IR group, that was characterized by an increment in heme oxygenase-1 (HO-1) and an anti-inflammatory response mediated by a NFkB-p65 phosphorylation and IL-6 decrease, together with an increase in TGF-ß, and IL-10 expression, as well as in M2-macrophages. In addition, three episodes of IR downregulated endoplasmic reticulum (ER) stress markers expression, CHOP and BiP. Thus, repeated episodes of IR with 10-day intervals induced long-term renal protection accompanied with HO-1 overexpression and M2-macrophages increase.

Asunto(s)

Lesión Renal Aguda , Insuficiencia Renal Crónica , Daño por Reperfusión , Ratas , Animales , Hemo-Oxigenasa 1 , Daño por Reperfusión/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/metabolismo , Insuficiencia Renal Crónica/metabolismo , Riñón/metabolismo , Isquemia/complicaciones , Antiinflamatorios/farmacología , Hemo/farmacología

RESUMEN

The present study was designed to investigate the possible role of magnesium (Mg2+) on activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ) and inhibition of nuclear factor-KB (NFKB p65) in muscle to increase glucose transporter 4 (GLUT4) gene expression. Fifty rats were divided into five groups, namely non-diabetic control (NDC), Mg2+-treated non-diabetic control (Mg2+-NDC), chronic diabetic (CD), Mg2+-treated chronic diabetic (Mg2+-CD), and insulin-treated chronic diabetic (Ins-CD). Diabetes was induced with streptozotocin (STZ) injection. The Mg2+-CD and Mg2+-NDC groups received 10 g/l of magnesium sulfate (MgSO4) added to drinking water and Ins-CD group received 2.5 U/kg of insulin. The blood glucose level and body weight were measured every week. After 16 weeks, intraperitoneal glucose tolerance test (IPGTT) was done and then animals were decapitated, blood samples were taken to determine the plasma levels of Mg2+ and gastrocnemius muscle legs were isolated for both PPAR-γ and NFKB (p65) genes and proteins expression. Administration of MgSO4 improved IPGTT, lowered blood glucose levels and increased PPAR-γ gene and protein expression. Diabetes increased NFKB gene and protein expression. Although Mg2+ therapy could not decrease NFKB (p65) gene expression, the protein decreased by Mg2+ therapy. Insulin decreased NFKB (p65) gene and protein expression, without any effect on PPAR-γ gene and protein expression. According to our findings it seems that suppressing NFKB (p65) protein synthesis and increases in PPAR-γ gene and protein expression could help Mg2+ administration to decreases blood glucose levels. But decreasing in NFKB (p65) gene and protein expression help insulin to decrease blood glucose level.