Epoetin beta pegol prevents endothelial dysfunction as evaluated by flow-mediated dilation in chronic kidney disease rats

Serizawa, Kenichi; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Hirata, Michinori; Endo, Koichi

doi:10.1016/j.ejphar.2015.09.034

Cited by 13 publications

(14 citation statements)

References 52 publications

(52 reference statements)

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“…Previously, we also demonstrated that prophylactic administration of C.E.R.A. prevented the reduction of FMD in 5/6 nephrectomized rats . This study is the first report to indicate a therapeutic effect of C.E.R.A.…”

Section: Discussionsupporting

confidence: 75%

“…Our previous report showed that repeated treatment with C.E.R.A. reduced oxidative stress in the femoral arteries of 5/6 nephrectomized rats . In addition, it was also reported that treatment with C.E.R.A.…”

Section: Discussionmentioning

confidence: 89%

“…A previous report demonstrated that C.E.R.A. prevented the reduction of FMD in CKD rats . However, there is as yet no evidence about the effect of C.E.R.A.…”

Section: Introductionmentioning

confidence: 94%

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Epoetin beta pegol ameliorates flow‐mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats

Serizawa¹,

Tashiro²,

Kawasaki³

et al. 2017

Cardiovascular Therapeutics

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SummaryBackground/AimsPatients with diabetic nephropathy have a high cardiovascular mortality. Epoetin beta pegol (continuous erythropoietin receptor activator, C.E.R.A.) is a drug for the treatment of renal anemia. In this study, we investigated the effect of C.E.R.A. on vascular endothelial function as evaluated by flow‐mediated dilation (FMD) and the relationship between hematopoiesis and FMD in diabetic nephropathy rats.MethodsMale Spontaneously Diabetic Torii rats (SDT, 22 weeks old) were used. C.E.R.A. (0.6, 1.2 μg/kg) was administered subcutaneously once every 2 weeks for 8 weeks. At 1 week after last administration (31 weeks old), we assessed FMD in the femoral arteries of anesthetized rats using a high‐resolution ultrasound system. FMD was also measured 1 week after single C.E.R.A. treatment (5.0 μg/kg) to examine the influence of hematopoiesis.ResultsFlow‐mediated dilation was significantly decreased in SDT rats before the start of C.E.R.A. treatment (22 weeks old). Repeated administration of C.E.R.A. dose‐dependently improved FMD in SDT rats (31 weeks old) without changing blood glucose, nitroglycerin‐induced vasodilation, or kidney function. Long‐term administration of C.E.R.A. improved the state of endothelial nitric oxide synthase uncoupling in the femoral arteries of SDT rats, which showed a positive correlation with FMD. On the other hand, there was no correlation between FMD and Hb or Hct in SDT rats. Furthermore, at 1 week after single administration of C.E.R.A., FMD was not significantly improved although hemoglobin levels were comparable with levels following long‐term C.E.R.A. treatment.ConclusionLong‐term treatment with C.E.R.A. improved FMD in SDT rats even after onset of endothelial dysfunction.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 89%

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Epoetin beta pegol ameliorates flow‐mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats

Serizawa¹,

Tashiro²,

Kawasaki³

et al. 2017

Cardiovascular Therapeutics

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“…For instance, EPO has been shown to prevent podocyte injury-induced nephrotic syndrome [63,64] and improve the endothelial function in 5/6 nephrectomized rats [65]. Interestingly, Eren et al found that EPO attenuated albuminuria and reduced tubular injury, inflammation, and interstitial fibrosis by inhibiting inflammatory markers and oxidative stress [66].…”

Section: Mechanisms Underlying the Renoprotection Exerted By Sglt2mentioning

confidence: 99%

SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy

Kawanami

Matoba

Takeda

et al. 2017

IJMS

136

103

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Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) worldwide. Glycemic and blood pressure (BP) control are important but not sufficient to attenuate the incidence and progression of DN. Sodium–glucose cotransporter (SGLT) 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D) and type 2 diabetes (T2D), indicating a potential renoprotective effect beyond glucose reduction. Renoprotection by SGLT2 inhibitors has been demonstrated in T2D patients with a high cardiovascular risk in randomized controlled trials (RCTs). These favorable effects of SGLT2 inhibitors are explained by several potential mechanisms, including the attenuation of glomerular hyperfiltration, inflammation and oxidative stress. In this review article, we discuss the renoprotective effects of SGLT2 inhibitors by integrating experimental findings with the available clinical data.

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“…Increased incidence of cardiovascular system dysfunction is associated with chronic kidney disease (CKD) (Serizawa et al, 2015). Alterations in the kidneys and heart occur in CKD (Hernández-Reséndiz et al, 2015;Thaung et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Impact of liraglutide versus atorvastatin on cardiovascular changes in rat model of adenine induced chronic renal failure

Shata¹,

Elmorsy²,

Elesawy³

et al. 2017

Afr. J. Pharm. Pharmacol.

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The prevalence of cardiovascular changes markedly increases with deterioration of patient's renal function and can stack up 65 to 70% in end-stage renal disease. A rapid fall in renal function is often associated with uncontrolled congestive heart failure. Beyond their lipid-lowering effect, statins have been shown to protect the heart in different diseases. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue, used to control diabetes. It improves cardiac dysfunction in non-diabetics, but underlying mechanisms remain to some extent, unclear. Fifty two male Sprague-Dawley rats weighing 200 to 250 g were grouped into negative control, positive control, liraglutide treated group (0.3 mg/kg), atorvastatin treated group (10 mg/kg), liraglutide and atorvastatin treated group (0.3 and 10 mg/kg, respectively), liraglutide and atorvastatin treated group (0.15 and 5 mg/kg, respectively). Combination of both drugs significantly reduce creatine phosphokinase isoenzyme (CK-MB) in both doses (p<0.008, p <0.002) and lactate dehydrognase (LDH) (p<0.04, p<0.01). Liraglutide alone or in combination with atorvastatin in both doses (p<0.02, p<0.01 and p<0.01) significantly increased superoxide dismutase (SOD). Atorvastatin alone (p<0.02) or in combination with liraglutide in both doses (p<0.001, p<0.001) induced a significant decrease of malondialdehyde (MDA). Atorvastatin alone (p<0.01) or in combination with liraglutide in both doses induced a significant amelioration of nitric oxide (NO) and cholesterol (p<0.01 and p<0.02). Significant improvements in blood urea nitrogen (BUN) and glucose profile were seen with all tested drugs either single or in combination. Combined implementation of both drugs improves histopathological changes of cardiac muscle fibres. Liraglutide has promising effects on cardiovascular changes in adenine induced chronic nephropathy through modulation of LDH, CK-MB and improvement of NO and SOD. Also, it can mitigate fibrosis and cardiac tissue changes. Its effects markedly increase in conjunction with atorvastatin. Combined administration of liraglutide and atorvastatin in a high dose has a reliable effect on improving outcome in biochemical and histopthological cardiac muscle fibers changes.

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Epoetin beta pegol prevents endothelial dysfunction as evaluated by flow-mediated dilation in chronic kidney disease rats

Cited by 13 publications

References 52 publications

Epoetin beta pegol ameliorates flow‐mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats

Epoetin beta pegol ameliorates flow‐mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats

SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy

Impact of liraglutide versus atorvastatin on cardiovascular changes in rat model of adenine induced chronic renal failure

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