The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats

Department of Physiology, Medical Faculty, Dumlupinar University, Central Campus, Tavsanlı Road, 43270 Kutahya, Turkey.
Molecular Biology Reports (Impact Factor: 2.02). 06/2012; 39(10):9775-82. DOI: 10.1007/s11033-012-1843-1
Source: PubMed


The aim of the present study was to evaluate the effects of phosphodiesterase type 5 (PDE5) inhibitory drugs, Tadalafil and Sildenafil, on inducible NOS (iNOS), endothelial NOS (eNOS) and p53 genes expressions and apoptosis in ischemia/reperfusion (I/R) induced oxidative injury in rat renal tissue. Eighty Sprague-Dawley rats (300-350 g) were divided into four groups. In ischemia/reperfusion group, rats were subjected to renal ischemia by clamping the left pedicle for 60 min, and then reperfused for 90 min. On the other hand, in other two groups the rats were individually pretreated with Tadalafil and Sildenafil 1 h before the induction of ischemia. Malondialdehyde (MDA) is determined in renal tissue homogenates by high-performance liquid chromatography, the number of apoptotic cell were calculated by TUNEL method and p53 and eNOS expression were detected with immunohistochemistry. On the other hand, myeloperoxidase (MPO) levels were measured by spectrophotometric method and the mRNA level of iNOS in renal tissue was determined by Real-time PCR (RT-PCR). Our results indicate that MDA and MPO levels were increased in the I/R group than those in the control group. Both Tadalafil and Sildenafil treatment decreased the MDA levels in ischemia/reperfusion group, whereas this effect was more potent with Sildenafil. RT-PCR results showed that, iNOS gen expression increased in the I/R group, but decreased in the PDE5 inhibitory drugs treated group. Apoptotic cells, eNOS levels and p53 positive cells were also decreased in PDE5 inhibitory drugs treated group. We suggest that Tadalafil and Sildenafil have beneficial effects against I/R related renal tissue injury and this protective effect is clearer for Sildenafil than Tadalafil.

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    • "In the present study, the ability of sildenafil to ameliorate gentamicin-induced elevation in malondialdehyde level is consistent with the findings of Cadirci et al. [7] who showed that sildenafil decreases malondialdehyde in the kidney tissues of cecal ligation and puncture-induced septic rats. Moreover, sildenafil treatment decreased MDA levels in renal ischemia-reperfusion injury in rats [14]. This inhibitory effect of sildenafil on lipid peroxidation may be a result of its suppressing effect on iNOS expression [15]. "
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    ABSTRACT: Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.
    Journal of Toxicology 07/2014; 2014(10):489382. DOI:10.1155/2014/489382
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    • "Given the reduced blood flow to the clipped kidney, oxygen deprivation and oxidative stress are unavoidable [55,56]. In this context, ROS overproduction reduces NO bioavailability in the renal vasculature via a scavenging effect and/or NOS uncoupling, leading to the increased production of •O2– and H2O2[4,57-59]. "
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    ABSTRACT: Background/aims: To evaluate the effects of sildenafil on antioxidant enzyme activities, lipid peroxidation and histopathological changes in ovarian tissue after ischemia-reperfusion (I/R) injury in a rat model. Methods: A total of 18 adult female Wistar albino rats weighing 200-250 g were studied as follows: (1) control group: sham operation, (2) I/R group: 3 h of reperfusion after 3 h of ischemia and (3) I/R + sildenafil group: 3 h of reperfusion after 3 h of ischemia; half an hour before reperfusion, sildenafil (1.4 mg·kg(-1)) was given by oral gavage. At the end of the reperfusion periods, the ovarian tissues were removed for histopathological examination and to determine malondialdehyde (MDA) levels and glutathione peroxidase, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities. Results: The I/R group had higher ovarian tissue MDA levels than the control group and the IR + sildenafil group (p = 0.016 and p = 0.044, respectively). MPO activity was lower in the IR + sildenafil group compared with the I/R group (p = 0.022). SOD activity was lower in the I/R group compared with the control group and the I/R + sildenafil group (p = 0.030 and p = 0.015, respectively). The I/R + sildenafil group had improved histological appearance which was not different to the control group (p > 0.05). Conclusion: The biochemical and histopathological results of this experimental study demonstrated that I/R injury in the ovary is ameliorated by sildenafil treatment.
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