Renoprotective effects of telmisartan in the 5/6 nephrectomised rats

Tsunenari, Ichiro; Ohmura, Tsuyoshi; Seidler, Randolph; Chachin, Motohiko; Hayashi, Toshihiro; Konomi, Ayako; Matsumaru, Takehisa; Sumida, Toshiyuki; Hayashi, Naoyuki; Horie, Yoshiharu

doi:10.3317/jraas.2007.017

Cited by 27 publications

(18 citation statements)

References 33 publications

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“…We further speculated by blocking the actions of TNF-␣ and IL-1␤ that we will be able to reduce renal dysfunction even when the therapy is started after the onset of proteinuria. We also used enalapril as a positive control for these studies because ANG II is a known inflammatory mediator and angiotensin-converting enzyme inhibitors (ACEI) are known to ameliorate both experimental and human renal failure (46,56).…”

mentioning

confidence: 99%

Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in ⅚ nephrectomized rats: role of phospholipase and cyclooxygenase

Ghosh¹,

Krieg²,

Massey³

et al. 2012

American Journal of Physiology-Renal Physiology

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Ghosh SS, Krieg R, Massey HD, Sica DA, Fakhry I, Ghosh S, Gehr TW. Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in 5 ⁄6 nephrectomized rats: role of phospholipase and cyclooxygenase. Am J Physiol Renal Physiol 302: F439-F454, 2012. First published October 26, 2011 doi:10.1152/ajprenal.00356.2010.-Previously, we showed that curcumin prevents chronic kidney disease (CKD) development in 5 ⁄6 nephrectomized (Nx) rats when given within 1 wk after Nx (Ghosh SS, Massey HD, Krieg R, Fazelbhoy ZA, Ghosh S, Sica DA, Fakhry I, Gehr TW. Am J Physiol Renal Physiol 296: F1146 -F1157, 2009). To better mimic the scenario for renal disease in humans, we began curcumin and enalapril therapy when proteinuria was already established. We hypothesized that curcumin, by blocking the inflammatory mediators TNF-␣ and IL-1␤, could also reduce cyclooxygenase (COX) and phospholipase expression in the kidney. Nx animals were divided into untreated Nx, curcumin-treated, and enalapril-treated groups. Curcumin (75 mg/kg) and enalapril (10 mg/kg) were administered for 10 wk. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was comparably reduced by curcumin and enalapril, with only enalapril significantly lowering blood pressure. Compared with controls, Nx animals had higher plasma/kidney TNF-␣ and IL-1␤, which were reduced by curcumin and enalapril treatment. Nx animals had significantly elevated kidney levels of cytosolic PLA 2, calcium-independent intracellular PLA 2, COX 1, and COX 2, which were comparably reduced by curcumin and enalapril. Studies in mesangial cells and macrophages were carried out to establish that the in vivo increase in PLA 2 and COX were mediated by TNF-␣ and IL-1␤ and that curcumin, by antagonizing the cytokines, could significantly reduce both PLA2 and COX. We conclude that curcumin ameliorates CKD by blocking inflammatory signals even if it is given at a later stage of the disease.

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confidence: 99%

Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in ⅚ nephrectomized rats: role of phospholipase and cyclooxygenase

Ghosh¹,

Krieg²,

Massey³

et al. 2012

American Journal of Physiology-Renal Physiology

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“…The renoprotective effect of telmisartan was also demonstrated in spontaneously hypertensive rats, 11 partially nephrectomized rats, 12 and cyclosporine A-induced nephrotoxicity in pigs. 13 In addition, telmisartan possesses antioxidant and anti-inflammatory effects independent of AT1 receptor-blocking activity.…”

Section: Introductionmentioning

confidence: 84%

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

et al. 2010

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It was demonstrated that fenofibrate and telmisartan exerted renoprotective effects in ischemia/reperfusion (I/R) injury. Because the combination of fenofibrate and telmisartan synergistically enhanced peroxisome proliferator-activated receptor (PPAR) activation, we hypothesized that the combination of both drugs may exert prolonged beneficial effects in renal I/R injury than fenofibrate alone. Forty-eight male Wistar albino rats were divided into eight groups. Hyperlipidemia was induced by cholesterol feeding for 4 weeks. At the end of the fourth week, renal I/R injury was performed by occlusion of both renal vascular pedicles for 60 minutes, followed by 24 hours of reperfusion. In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia. At the end of the experiment, blood and kidneys were isolated for biochemical and histological analysis. I/R in hyperlipidemic rat shows significantly increased lipid peroxidation, nitric oxide, and myeloperoxidase activity, and depletion of antioxidant enzyme compared with control rats, and that was significantly restored after fenofibrate and telmisartan treatment. Also, significant increases in serum homocysteine level were detected following I/R. Fenofibrate treatment further elevated homocysteine level, which was reduced by telmisartan in combination with fenofibrate. The most significant histological damage was found in the hyperlipidemic rat subjected to renal I/R, which was reduced significantly with combination therapy. The results of this study concluded that fenofibrate alone and in combination with telmisartan significantly ameliorated renal I/R injury. The additive beneficial effect of telmisartan is predicted to reduce homocysteine-induced oxidative stress through reduced nitric oxide production during I/R.

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“…The 5/6 nephrectomy model is a common one for CRF [17,18] . Sclerosis of the residual nephrons gradually occurs in response to the high perfusion, high pressure, and high filtration caused by 5/6 nephrectomy.…”

Section: Discussionmentioning

confidence: 99%

Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure

Xie

et al. 2012

Acta Pharmacol Sin

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Aim: Sulodexide, a glycosaminoglycan, could reduce albuminuria in diabetic patients. The aim of this study was to determine whether sulodexide could be used to treat chronic kidney failure in rats. Methods: Sixty Wistar rats undergone 5/6 nephrectomy, then were randomly divided into 4 groups: the model group, sulodexide group (sulodexide 5 mg/kg per day, im), irbesartan group irbesartan (20 mg/kg per day, ig) and sulodexide plus irbesartan group. Another 12 rats were enrolled into the sham operation group. After the treatments for 4, 8 and 12 weeks, urinary protein and serum creatinine levels were measured. After 12 weeks, serum cholesterin and triglycerides levels were measured, and the degrees of glomerular sclerosis and renal tubulointerstitial fibrosis were scored. The expression of aminopeptidase P (JG-12) in the renal tissue was examined using immunohistochemical staining. The renal expressions of endothelial nitric oxide synthase (eNOS) and tissue type plasminogen activator (tPA) were detected with RT-PCR and Western blot. Results: Proteinuria was markedly attenuated in the sulodexide-treated groups. After 4 and 8 weeks only the sulodexide-treated groups showed significant reduction in serum creatinine; while after 12 weeks all the three treatment groups showed significant reduction in serum creatinine. Furthermore, all the three treatment groups showed significant reduction in the scores of glomerular sclerosis and tubulointerstitial fibrosis. The glomerular expression of JG-12 was increased in both the sulodexide group and the sulodexide plus irbesartan group, but not in the irbesartan group. The eNOS mRNA and protein expression was decreased and the tPA mRNA and protein expression was significantly increased in the model group compared with Sham group. Sulodexide, irbesartan, and their combination reversed the decrease of eNOS expression but increased the tPA expression much more compared with model group. Conclusion: Sulodexide was similar to irbesartan that can decrease proteinuria and attenuate renal lesions in 5/6 nephrectomy rats. The renal protection by sulodexide might be achieved via its impact on renal vascular endothelial cells.

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Renoprotective effects of telmisartan in the 5/6 nephrectomised rats

Cited by 27 publications

References 33 publications

Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in ⅚ nephrectomized rats: role of phospholipase and cyclooxygenase

Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in ⅚ nephrectomized rats: role of phospholipase and cyclooxygenase

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure

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