Sildenafil attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity

Lee, Kang Wook; Jeong, Jin Young; Lim, Beom Jin; Chang, Yoon-Kyung; Lee, Sang-Ju; Na, Ki Young; Shin, Young-Tai; Choi, Dae Eun

doi:10.1016/j.tox.2008.12.017

Cited by 76 publications

(64 citation statements)

References 21 publications

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“…They have been shown to exert a potent antiproliferative effect, preventing mesangial cell proliferation and extracellular matrix expansion; outcomes that cannot be replicated through a comparable reduction in BP using hydralazine. 69,70 Studies have also demonstrated the beneficial effects of PDE5 inhibition on renal cell apoptosis, 68,71 oxidative stress, 72 and inflammation 73 in CKD models. Therefore, preclinical data support this approach.…”

Section: Pde Type 5 Inhibitionmentioning

confidence: 99%

Potential Therapeutic Role of Phosphodiesterase Type 5 Inhibition in Hypertension and Chronic Kidney Disease

Brown

Dhaun²,

Goddard³

et al. 2014

Hypertension

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Section: Pde Type 5 Inhibitionmentioning

confidence: 99%

Potential Therapeutic Role of Phosphodiesterase Type 5 Inhibition in Hypertension and Chronic Kidney Disease

Brown

Dhaun²,

Goddard³

et al. 2014

Hypertension

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“…Cysteamine which is used in the treatment of cystinosis enters the lysosome by a specific transporter for aminothiols or aminosulfides (Pisoni et al, 1995). Lee et al (2009) suggested that SIL has a renoprotective effect and attenuates experimental cisplatin-induced nephrotoxicity by preventing apoptosis. This finding with the findings of the current study may endorse further clinical investigations in human to evaluate the possible usefulness of SIL with cyteamine in cases of cystinosis to prevent its possible ulcerogenic effect on the duodenum and prevent the detrimental effect of cystinosis on the kidney.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of sildenafil against cysteamine induced duodenal ulcer in Wistar rats

Elberry¹

2013

Afr. J. Pharm. Pharmacol.

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The aim of the current study was to investigate the possible protective effect of sildenafil (SIL) on cysteamine induced peptic ulcer in Wistar rats. Rats were randomly divided into five groups; six animals each. Normal control group; in which animals received an aqueous solution of Tween 80 (1 ml/kg) as a vehicle, two doses orally at an interval of 4 h. SIL group, in which animals received 25 mg/kg SIL orally 30 min before vehicle administration. Cysteamine group; in which duodenal ulceration was induced by two oral doses of cysteamine-HCl (450 mg/kg in 10% aqueous solution) at an interval of 4 h. Cysteamine+omepeazole group; in which animals were pretreated with 20 mg/kg omeprazole orally 30 min before cysteamine. Cysteamine+SIL group; in which animals were pretreated with 25 mg/kg SIL orally, 30 min before cysteamine. Twenty-four hours after the last dose of vehicle or cysteamine, rats were euthanized and the duodena were removed to determine the number of ulcers, ulcer surface area, ulcer score and ulcer index as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS) in tissue homogenates referring to the malondialdehyde, reduced glutathione (GSH) and oxidized glutathione (GSSG). The results of the present study showed that SIL treatment decreased the number of ulcers, the ulcer surface area, the ulcer score and the ulcer index in the cysteamine induced duodenal ulcer. Moreover, SIL ameliorated the biochemical changes that were induced by cysteamine. In conclusion, SIL attenuates experimentally induced peptic ulceration using cysteamine partially through induction of nitrogen oxide (NO) and antioxidant effect which may be useful in the treatment of cystinosis.

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“…As it has been demonstrated that PDE inhibitors alone (including ZAP) reduce the nephrotoxicity in AKI models (14,15,16,47,48), we used a suboptimal dose of ZAP, settled in 5-10 mg/kg body weight, (49,50).…”

Section: The Protective Effect Of Ilk Depletion On Cis-induced Aki Dementioning

confidence: 99%

“…Furthermore, there is abundant literature pointing to the relevant cytoprotective effect of agents that increase cGMP, which have been shown to be beneficial under several clinical and experimental conditions (10)(11)(12) including renal protection under nephrotoxic agents (13)(14)(15)(16). However, the nature of this protection has not been definitively elucidated.…”

mentioning

confidence: 99%

Renal Integrin-Linked Kinase Depletion Induces Kidney cGMP-Axis Upregulation: Consequences on Basal and Acutely Damaged Renal Function

Cano-Peñalver

Griera

García-Jérez

et al. 2015

Mol Med

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Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and produces cGMP, which activates cGMP-dependent protein kinases (PKG) and is hydrolyzed by specific phosphodiesterases (PDE). The vasodilatory and cytoprotective capacity of cGMP-axis activation results in a therapeutic strategy for several pathologies. Integrin-linked kinase (ILK), a major scaffold protein between the extracellular matrix and intracellular signaling pathways, may modulate the expression and functionality of the cGMP-axis-related proteins. We introduce ILK as a novel modulator in renal homeostasis as well as a potential target for cisplatin (CIS)-induced acute kidney injury (AKI) improvement. We used an adult mice model of depletion of ILK (cKD-ILK), which showed basal increase of sGC and PKG expressions and activities in renal cortex when compared with wildtype (WT) littermates. Twenty-four h activation of sGC activation with NO enhanced the filtration rate in cKD-ILK. During AKI, cKD-ILK maintained the cGMP-axis upregulation with consequent filtration rates enhancement and ameliorated CIS-dependent tubular epithelial-to-mesenchymal transition and inflammation and markers. To emphasize the role of cGMP-axis upregulation due to ILK depletion, we modulated the cGMP axis under AKI in vivo and in renal cultured cells. A suboptimal dose of the PDE inhibitor ZAP enhanced the beneficial effects of the ILK depletion in AKI mice. On the other hand, CIS increased contractility-related events in cultured glomerular mesangial cells and necrosis rates in cultured tubular cells; ILK depletion protected the cells while sGC blockade with ODQ fully recovered the damage.

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Sildenafil attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity

Cited by 76 publications

References 21 publications

Potential Therapeutic Role of Phosphodiesterase Type 5 Inhibition in Hypertension and Chronic Kidney Disease

Potential Therapeutic Role of Phosphodiesterase Type 5 Inhibition in Hypertension and Chronic Kidney Disease

Protective effect of sildenafil against cysteamine induced duodenal ulcer in Wistar rats

Renal Integrin-Linked Kinase Depletion Induces Kidney cGMP-Axis Upregulation: Consequences on Basal and Acutely Damaged Renal Function

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