Simvastatin improves the healing of infected skin wounds of rats

Rêgo, Amália Cínthia Meneses; Filho, Irami Araújo; Damasceno, Bolívar Ponciano Goulart de Lima; Egito, Eryvaldo Sócrates Tabosa do; Silveira, Ivanaldo Amâncio da; Brandão-Neto, José; Medeiros, Aldo Cunha

doi:10.1590/s0102-86502007000700012

Cited by 40 publications

(34 citation statements)

References 26 publications

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“…It has been also demonstrated that statin decreases the expression of cytokines 26 . Moreover, recent experimental studies have demonstrated the antiinflammatory action of statins in improving the healing of infected wounds in rats 6 , as well as in abdominal sepsis 7 .…”

Section: Discussionmentioning

confidence: 99%

“…Statins have been shown to be especially effective in reducing low-density lipoprotein cholesterol (LDL) and, to a lesser extent, triglyceride levels 2 . Statins' antiinflammatory effects have been proposed not only to reduce cardiovascular disease, but also to help improve other conditions that are not influenced by lipid levels, including rheumatoid arthritis 3 , stroke 4 , graft rejection 5 and infection 6,7 .…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

et al. 2010

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PURPOSE: Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. METHODS: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-α, IL-1β, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. RESULTS: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-α, IL-1β and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. CONCLUSION: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

et al. 2010

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“…Rat open skin wounds infected with Gram-positive and -negative Review bacteria were treated with topical simvastatin (10 mg/ml) or saline. Along with lower expression of TNF-a and IL-1b, researchers found infection in only one out of seven rats in the simvastatin treated group, while all rats in the saline group showed polymicrobial infections [68]. The ability of statins to reduce infection was also apparent in a study assessing the use of statins on methicillin-susceptible and -resistant Staphylococcus aureus, and vancomycin-sensitive and -resistant enterococci blood culture isolates.…”

Section: Statins and Bacterial Infectionmentioning

confidence: 99%

Statins as potential therapeutic agents for healing disorders

Stojadinović

Lebrun

Pastar

et al. 2010

Expert Review of Dermatology

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Statins, HMG-CoA reductase inhibitors, are common cholesterol-lowering drugs. Recent studies suggest that statins may have potential as novel treatments for diverse conditions, ranging from sepsis and inflammatory diseases to chronic wounds and bone fractures. The diverse pleiotropic actions of statins are probably related to reduced isoprenylation of downstream targets of the mevalonate pathway and their binding to several nuclear hormone receptors. Statins exert their anti-inflammatory effect by inhibiting the release of C-reactive peptide, chemokines, cytokines and adhesion molecules, which may make them a powerful addition to the dermatologic antiinflammatory medication arsenal. Along with reducing inflammation, statins have the potential to heal chronic wounds by decreasing farnesyl pyrophosphate, facilitating vascular relaxation, promoting neovascularization and reducing bacterial load. A review of the literature elucidates that route of administration, dose and type of statin appear to impact the outcome. A better understanding of their effects at the cellular and molecular level in skin is necessary for their future use.

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“…Although inhibition of cholesterol synthesis and reduction in lipid levels are clinically important uses of the statins, they also show additional cholesterol-independent effects. These cholesterol-independent pleiotropic actions of statins involve immunomodulatory effects, decrease of oxidative stress, anabolic effects on bone, and stimulation of fracture healing (19 -22) and wound healing (23)(24)(25).…”

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confidence: 99%

Farnesyl Pyrophosphate Inhibits Epithelialization and Wound Healing through the Glucocorticoid Receptor

Vukelic

Stojadinović

Pastar

et al. 2010

Journal of Biological Chemistry

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Farnesyl pyrophosphate (FPP), a key intermediate in the mevalonate pathway and protein farnesylation, can act as an agonist for several nuclear hormone receptors. Here we show a novel mechanism by which FPP inhibits wound healing acting as an agonist for glucocorticoid receptor (GR). Elevation of endogenous FPP by the squalene synthetase inhibitor zaragozic acid A (ZGA) or addition of FPP to the cell culture medium results in activation and nuclear translocation of the GR, a known wound healing inhibitor. We used functional studies to evaluate the effects of FPP on wound healing. Both FPP and ZGA inhibited keratinocyte migration and epithelialization in vitro and ex vivo. These effects were independent of farnesylation and indicate that modulation of FPP levels in skin may be beneficial for wound healing. FPP inhibition of keratinocyte migration and wound healing proceeds, in part, by repression of the keratin 6 gene. Furthermore, we show that the 3-hydroxy-3-methylglutaryl-CoA-reductase inhibitor mevastatin, which blocks FPP formation, not only promotes epithelialization in acute wounds but also reverses the effect of ZGA on activation of the GR and inhibition of epithelialization. We conclude that FPP inhibits wound healing by acting as a GR agonist. Of special interest is that FPP is naturally present in cells prior to glucocorticoid synthesis and that FPP levels can be further altered by the statins. Therefore, our findings may provide a better understanding of the pleiotropic effects of statins as well as molecular mechanisms by which they may accelerate wound healing.

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Simvastatin improves the healing of infected skin wounds of rats

Abstract: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising.

Cited by 40 publications

References 26 publications

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

Statins as potential therapeutic agents for healing disorders

Farnesyl Pyrophosphate Inhibits Epithelialization and Wound Healing through the Glucocorticoid Receptor

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