Effects of pentoxifylline on gentamicin-induced nephrotoxicity

Kasap, Belde; Türkmen, Mehmet; Kıray, Müge; Kuralay, Filiz; Soylu, Alper; Tugyan, Kazim; Kavukçu, Salìh

doi:10.3109/0886022x.2013.828359

Cited by 10 publications

(9 citation statements)

References 23 publications

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“…In nephrotoxic animal models induced by gentamicin and amikacin, PTX showed antioxidative and renoprotective effects [11,18]. Wang et al [19] and Zhou et al [20] also reported its kidney protective effects by inhibiting the appearance of TNF-α, IL-1β, and NO and inhibiting tubulointerstitial fibrosis in animal models.…”

Section: Introductionmentioning

confidence: 97%

Effects of 1,7-Substituted Methylxanthine Derivatives on LPS-Stimulated Expression of Cytokines and Chemokines in Raw 264.7 and HK-2 Cells

Kang

Shin²

2015

Journal of Microbiology and Biotechnology

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Chronic kidney diseases are based on uncontrolled immunological and inflammatory responses to pathophysiological renal circumstances such as glomerulonephritis, which is caused by immunological mechanisms of glomerular inflammation with increased production of renal pro-inflammatory cytokines. Pentoxifylline (PTX) exhibits anti-inflammatory properties by inhibiting cytokine and chemokine production through aggregation of erythrocytes and thrombocytes. We synthesized a series of 1,7-substituted methylxanthine derivatives by the Traube purine reaction, and the formation of purine ring was completed through nitrosation, a reduction of the nitroso to the amine by catalytic hydrogenation as derivatives of PTX. Then we studied biological activities such as renal anti-inflammatory effects of the synthesized compounds in the production of cytokines such as nitric oxide (NO), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) and of chemokines such as monocyte chemoattractant protein-1 and IL-8 in Raw 264.7 and HK-2 cells. Renal antiinflammatory activities of this novel series of N-1 and N-7-substituted methylxanthine showed that the N-7 methyl-group-substituted analogs (S7b) showed selective 61% and 77% inhibition of the production of NO and IL-8. The other replacement of the N-1-(CH2)4COCH3 group, as in the case of compound S6c, also showed an effective 50% and 77% inhibition of TNF-α and IL-8 production in LPS-stimulated Raw 264.7 and HK-2 cells.

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Section: Introductionmentioning

confidence: 97%

Effects of 1,7-Substituted Methylxanthine Derivatives on LPS-Stimulated Expression of Cytokines and Chemokines in Raw 264.7 and HK-2 Cells

Kang

Shin²

2015

Journal of Microbiology and Biotechnology

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“…The pathogenesis of gentamicin nephrotoxicity involves multiple pathways, including oxidative stress, inflammation, reduced renal blood flow, and increased nitric oxide (NO) level [2, 3]. Several agents have been used, with various degrees of success, to ameliorate or prevent gentamicin nephrotoxicity [4–6]. …”

Section: Introductionmentioning

confidence: 99%

Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

Morsy

Ibrahim

Amin

et al. 2014

Journal of Toxicology

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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.

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“…The most common side effect of kanamycin is nephrotoxicity [2][3][4][5][6][7][8][9] and the drug accumulates in the kidneys 10-50 times more than in the plasma. Although it has been reported that kidney damage occurred in 25-50% of patients, pentoxifylline might show a renoprotective effect in some diseases resulting from its vasodilator, antioxidant, and microcirculatory features [9,11,15,22].…”

Section: Discussionmentioning

confidence: 99%

“…Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascular inflammation might also be observed in aminoglycoside-induced nephrotoxicity [9]. Pentoxifylline produces no histopathological changes or an induction of apoptosis in the kidneys [3], while necrosis and apoptosis of tubular epithelial cells, tubular dilatation, increased connective tissue mass in some areas of the interstitium, an enlarged glomerulus or Bowman's capsule, neutrophil or MNC infiltrates, and hemorrhage in some areas of the interstitium have been reported in amikacin-or gentamycin-induced nephrotoxicity [3,12,16,17]. In the current research, pentoxifylline prevented tubular damage induced by kanamycin, but did not inhibit infiltration by MNCs (Table 1, Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…The 32 rats were randomly divided into 4 groups as follows: control (n = 6), pentoxifylline (n = 6), kanamycin (n = 10), and kanamycin + pentoxifylline (n = 10). The control group received an intraperitoneal (IP) injection of 0.5 mL normal saline solution once/d (SID) for 20 d, the pentoxifylline group received an IP injection of 50 mg/kg pentoxifylline twice/d (BID) for 20 d (Trental amp™) 1 [3], the kanamycin group received a subcutaneous injection of 500 mg/kg kanamycin SID for 20 d (Kanovet enj sol™) 2 [14], and the kanamycin + pentoxifylline group received an SC injection of 500 mg/ kg kanamycin SID for 20 d together with an IP injection of 50 mg/kg pentoxifylline BID for 20 d. At the end of the 20 d period, blood samples were taken from the heart by cardiac puncture under general anesthesia (60 mg/kg sodium thiopental, IP, Pental sodium) 3 . After the blood samples were taken, the rats were euthanized by cervical dislocation under general anesthesia.…”

Section: Methodsmentioning

confidence: 99%

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Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats

Çorum

Özdemir

Hitit

et al. 2018

Acta Scientiae. Vet.

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Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the longterm. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents,can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented byusing pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objectiveof this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage.Materials, Methods & Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline,kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normalsaline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifyllinetwice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injectionsof 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac punctureunder general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediatelyremoved, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogramparameters were measured using a blood cell count apparatus and serum biochemical parameters were measured usingan autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifyllinesignificantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubulardilatation. Increases in relative kidney weights (P < 0.05) and in interstitial mononuclear cell (MNC) infiltrates wereobserved in the kanamycin and kanamycin + pentoxifylline groups compared to those in the control and pentoxifyllinegroups. Statistically significant changes were determined in the levels of some hemogram and biochemical parameterswithin reference ranges (P < 0.05).Discussion: In this study, both tubular degeneration and dilatation were observed in the kanamycin group. Pentoxifyllineinhibited (P < 0.05) kanamycin-induced tubular degeneration and appeared to also reduce tubular dilatation, although thisreduction was not significant. Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascularinflammation might also be observed in aminoglycoside-induced nephrotoxicity. In current research, pentoxifylline preventedtubular damage induced by kanamycin, but did not inhibit infiltration by MNCs. Pentoxifylline also amelioratedamikacin- or gentamycin-induced histopathologic changes, especially those associated with tubular structures. The protectiveeffects of pentoxifylline on kanamycin-induced tubular nephrotoxicity in this research might be a result of its stimulatingthe production of prostaglandin, a vasodilator, and of its improving microcirculation. Although the anti-inflammatoryeffects of pentoxifylline have been reported, these did not inhibit kanamycin-induced infiltration by interstitial MNCs inthe present study. These results could indicate that the anti-inflammatory effects of pentoxifylline are not obvious and/orare dose dependent. Statistically significantly changes were determined in the levels of some hemogram and biochemicalparameters in reference ranges. However, these changes were within the reference ranges for rats. These results suggestedthat kanamycin-induced tubular degeneration and dilatation might be prevented by administering pentoxifylline.

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Effects of pentoxifylline on gentamicin-induced nephrotoxicity

Cited by 10 publications

References 23 publications

Effects of 1,7-Substituted Methylxanthine Derivatives on LPS-Stimulated Expression of Cytokines and Chemokines in Raw 264.7 and HK-2 Cells

Effects of 1,7-Substituted Methylxanthine Derivatives on LPS-Stimulated Expression of Cytokines and Chemokines in Raw 264.7 and HK-2 Cells

Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats

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