No abstract

1. Recombinant human erythropoietin (rHuEPO) has been used for the management of renal anaemia. Recent studies suggest pleiotropic properties of rHuEPO in various tissues. The aim of the present study was to investigate the vasoprotective effects of rHuEPO in renal failure rats. 2. Rats subjected to 5/6 and 17/18 nephrectomy (5/6Nx and 17/18Nx rats, respectively) were treated with rHuEPO (75 U/kg, s.c.) three times a week for 2 weeks. 3. Administration of rHuEPO to 5/6Nx or 17/18Nx rats had no effect on systolic blood pressure or decreased haematocrit. However, rHuEPO treatment normalized proteinuria and creatinine clearance in 5/6Nx, but not in 17/18Nx, rats. 4. Vasodilation in response to acetylcholine in aortic rings was impaired in 5/6Nx and 17/18Nx rats and improved by rHuEPO in both groups. Immunohistochemical analysis revealed that macrophage infiltration into adventitial areas and the expression of osteopontin were enhanced in aortas from 5/6Nx and 17/18Nx rats, but that rHuEPO suppressed these effects. In addition, rHuEPO attenuated medial hyperplasia and NADPH oxidase-derived superoxide production in 5/6Nx and 17/18Nx rats. 5. Activation of the Akt signalling pathway was evident in rHuEPO-treated rats as the increased expression of phosphorylated Akt and glycogen synthase kinase-3β. Treatment with rHuEPO restored the expression of phosphorylated endothelial nitric oxide synthase in the aorta and urinary excretion of NO(x) in nephrectomized rats. 6. These results suggest that a low dose of rHuEPO results in the normalization of endothelial function, vascular inflammation and oxidative stress in rats with renal ablation beyond haematopoiesis. In addition, these vasoprotective effects are observed even in a state of deteriorating renal dysfunction.

No abstract

Erythropoietin (EPO) has been used for the management of renal anemia. Recent studies suggest the pleiotropic properties of EPO in various tissues such as brain, kidney and vasculature. Diabetes mellitus is a major risk for development of vascular impairment. The aim of the present study was to investigate the hypothesis that EPO would be beneficial in inhibiting diabetic macroangiopathy. Recombinant human EPO (rHuEPO; 150 U/kg, 3 times/week, s.c.) was administered to streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.v.) significantly increased macrophage infiltration and adhesion molecules, monocyte chemoattractant protein-1 and osteopontin mRNA levels in the aorta. These inflammatory changes were suppressed by rHuEPO. Vasodilation in response to acetylcholine in the aortic ring was impaired in the diabetic rats, and improved by rHuEPO. rHuEPO inhibited the aortic expression of mRNA for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the NADPH oxidase-dependent superoxide production and the increase in plasma malondialdehyde concentration in diabetic rats. rHuEPO also decreased the level of the receptor for advanced glycation end products in the aorta. We also found an increased expression of phospho-Akt and endothelial nitric oxide synthase and plasma NOx level in the rHuEPO-treated group. On the other hand, rHuEPO did not affect blood glucose levels, hemoglobin A_1c, blood pressure or hematocrit in diabetic rats. These results indicate that rHuEPO exerts pleiotropic antioxidant and anti-inflammatory properties in diabetic rat aorta.

The influence of ciclosporin (Cs) on liver regeneration was studied in rats and mice with or without thymus after two-third hepatectomy. Rats were treated at –24, 0, and +24 h posthepatectomy with oral Cs, 5, 10, or 20 mg/kg. Before hepatectomy, mice were given a 4-day course of Cs 10 mg/kg. The peak mitosis (30 h posthepatectomy) of remnant hepatocytes in rats was doubled by the two lower dosages of Cs but was suppressed by the highest dosage compared with control. In addition, the rise in serum transaminase and total bilirubin concentrations was proportionate to the increase in Cs dosage given. Cs increased hepatocyte division in thymic mice but was hepatotoxic in athymic nude mice. These data present evidence that Cs is both hepatotrophic and hepatotoxic in regenerating liver.