Triiodothyronine attenuates the progression of renal injury in a rat model of chronic kidney disease

2018 ◽  
Vol 96 (6) ◽  
pp. 603-610 ◽  
Author(s):  
Sahar M. El Agaty
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
Renal Injury ◽  
Serum Levels ◽  
Female Rats ◽  
Renal Tubules ◽  
Oxide Synthase ◽  
Remnant Kidney

This study was designed to investigate whether and how triiodothyronine (T3) affects renal function in an experimental model of chronic kidney disease. Twenty-four female rats were divided into the following groups: sham-operated control group (n = 8), 5/6 nephrectomized group (Nx, n = 8), and 5/6 nephrectomized group treated with T3 for 2 weeks (T3-Nx, n = 8). T3 administration significantly decreased serum levels of urea, creatinine, tumour necrosis factorα, and interleukin-6 compared with serum levels in the Nx group. The levels of malondialdehyde, transforming growth factor β, fibronectin, and collagen IV, as well as the expression of inducible nitric oxide synthase, nuclear factor κB, poly(ADP-ribose) polymerase, caspase-3, and Bax were all significantly decreased, though not normalized, in the remnant kidney of rats in the T3-Nx group compared with Nx rats. Glutathione, heme oxygenase-1 levels, as well as endothelial nitric oxide synthase expression were increased in the remnant kidney of the T3-Nx group. Histological studies revealed focal necrosis of renal tubules associated with inflammatory cell infiltration and fibrosis in the Nx group. These changes were alleviated in T3-Nx rats. This study showed that T3 administration attenuated the clinical and histological signs of renal injury in 5/6 nephrectomized rats by mitigating renal oxidative stress, inflammation, apoptosis, and fibrosis.

scholarly journals Endothelial Nitric Oxide Synthase Gene Variation Associated With Chronic Kidney Disease After Liver Transplant

2010 ◽  
Vol 85 (9) ◽  
pp. 814-820 ◽  
Author(s):  
Kiran Bambha ◽  
W. Ray Kim ◽  
Charles B. Rosen ◽  
Rachel A. Pedersen ◽  
Cynthia Rys ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
Liver Transplant ◽  
Endothelial Nitric Oxide Synthase ◽  
Gene Variation ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Endothelial cell transfusion ameliorates endothelial dysfunction in 5/6 nephrectomized rats

2013 ◽  
Vol 305 (8) ◽  
pp. H1256-H1264 ◽  
Author(s):  
Maricica Pacurari ◽  
Dongqi Xing ◽  
Rob H. P. Hilgers ◽  
Yuan Yuan Guo ◽  
Zhengqin Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
Endothelial Nitric Oxide Synthase ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Endothelial dysfunction is prevalent in chronic kidney disease. This study tested the hypothesis that transfusion of rat aortic endothelial cells (ECs) ameliorates endothelial dysfunction in a rat model of chronic kidney disease. Male Sprague-Dawley rats underwent sham surgery or 5/6 nephrectomy (Nx). Five weeks after Nx, EC (1.5 × 106 cells/rat) or vehicle were transfused intravenously. One week later, vascular reactivity of mesenteric artery was assessed on a wire myograph. Sensitivity of endothelium-dependent relaxation to acetylcholine and maximum vasodilation were impaired by Nx and improved by EC transfusion. Using selective pharmacological nitric oxide synthase isoform inhibitors, we demonstrated that the negative effect of Nx on endothelial function and rescue by EC transfusion are, at least in part, endothelial nitric oxide synthase mediated. Plasma asymmetric dimethylarginine was increased by Nx and decreased by EC transfusion, whereas mRNA expression of dimethylarginine dimethylaminohydrolases 1 (DDAH1) was decreased by Nx and restored by EC transfusion. Immunohistochemical staining confirmed that local expression of DDAH1 is decreased by Nx and increased by EC transfusion. In conclusion, EC transfusion attenuates Nx-induced endothelium-dependent vascular dysfunction by regulating DDAH1 expression and enhancing endothelial nitric oxide synthase activity. These results suggest that EC-based therapy could provide a novel therapeutic strategy to improve vascular function in chronic kidney disease.

Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with chronic kidney disease

2011 ◽  
Vol 22 (6) ◽  
pp. 487-492 ◽  
Author(s):  
Manal F. Elshamaa ◽  
Samar Sabry ◽  
Ahmed Badr ◽  
Mostafa El-Ahmady ◽  
Eman A. Elghoroury ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
Endothelial Nitric Oxide Synthase ◽  
Vntr Polymorphism ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Sex-specific vascular responses of the rat aorta: effects of moderate term (intermediate stage) streptozotocin-induced diabetes

2016 ◽  
Vol 94 (4) ◽  
pp. 408-415 ◽  
Author(s):  
Xiaoyuan Han ◽  
Sonali Shaligram ◽  
Rui Zhang ◽  
Leigh Anderson ◽  
Roshanak Rahimian
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Intermediate Stage ◽  
Diabetic Rats ◽  
Female Rats ◽  
Diabetic Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Oxide Synthase

Hyperglycemia affects male and female vascular beds differently. We have previously shown that 1 week after the induction of diabetes with streptozotocin (STZ), male and female rats exhibit differences in aortic endothelial function. To examine this phenomenon further, aortic responses were studied in male and female rats 8 weeks after the induction of diabetes (intermediate stage). Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh) was measured in phenylephrine (PE) pre-contracted rat aortic rings. Concentration response curves to PE were generated before and after L-NAME, a nitric oxide synthase (NOS) inhibitor. Furthermore, mRNA expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase subunit (Nox1) were determined. At 8 weeks, diabetes impaired EDV to a greater extent in female than male aortae. Furthermore, the responsiveness to PE was significantly enhanced only in female diabetic rats, and basal NO, as indicated by the potentiation of the response to PE after L-NAME, was reduced in female diabetic rat aortae to the same levels as in males. In addition, eNOS mRNA expression was decreased, while the Nox1 expression was significantly enhanced in diabetic female rats. These results suggest that aortic function in female diabetic rats after 8 weeks exhibits a more prominent impairment and that NO may be involved.

scholarly journals Solubleα-Klotho Serum Levels in Chronic Kidney Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Silverio Rotondi ◽  
Marzia Pasquali ◽  
Lida Tartaglione ◽  
Maria Luisa Muci ◽  
Giusy Mandanici ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Clinical Significance ◽  
Serum Levels ◽  
Serum Phosphate ◽  
Renal Tubules ◽  
Ckd Stage ◽  
Tubular Transport ◽  
Negative Effect

Transmembraneα-Klotho (TM-Klotho), expressed in renal tubules, is a cofactor for FGF23-receptor. Circulating soluble-α-Klotho (s-Klotho) results from TM-Klotho shedding and acts on Phosphate (P) and Calcium (Ca) tubular transport. Decreased TM-Klotho, described in experimental chronic kidney disease (CKD), prevents actions of FGF23 and lessens circulating s-Klotho. Thus, levels of s-Klotho could represent a marker of CKD-MBD. To evaluate the clinical significance of s-Klotho in CKD we assayed serum s-Klotho and serum FGF23 in 68 patients (age58±15; eGFR45±21 mL/min). s-Klotho was lower than normal (519±183versus845±330 pg/mL,P<.0001) in renal patients and its reduction was detectable since CKD stage 2 (P<.01). s-Klotho correlated positively with eGFR and serum calcium (Cas) and negatively with serum phosphate (Ps), PTH and FGF23. FGF23 was higher than normal (73±51versus36±11,P<.0002) with significantly increased levels since CKD stage 2 (P<.001). Our data indicate a negative effect of renal disease on circulating s-Klotho starting very early in CKD. Assuming that s-Klotho mirrors TM-Klotho synthesis, low circulating s-Klotho seems to reflect the ensuing of tubular resistance to FGF23, which, accordingly, is increased. We endorse s-Klotho as an early marker of CKD-MBD.

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