Effects of statins beyond lipid lowering: Potential for clinical benefits

Almuti, Khalid; Rimawi, Rola; Spevack, Daniel M.; Ostfeld, Robert J.

doi:10.1016/j.ijcard.2005.05.056

Cited by 112 publications

(96 citation statements)

References 109 publications

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“…One agent that has shown potential in sepsis therapy is simvastatin, a lipid-lowering drug targeting 3-hydroxy-3-methylglytaryl coenzyme A (HMG-CoA) reductase, which also exhibits pleiotropic antiinflammatory, antiplatelet and vasodilatory activities (9)(10)(11)(12). Results of a randomized, doubleblind, placebo-controlled clinical trial associated simvastatin administration with lower levels of inflammatory cytokines in patients with acute bacterial infections while another study suggested that prior statin therapy may have a role in the primary prevention and management of severe sepsis syndrome (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway

Apaya

Lin

Chiou

et al. 2015

Mol Med

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Section: Introductionmentioning

confidence: 99%

Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway

Apaya

Lin

Chiou

et al. 2015

Mol Med

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“…Since then, their role in the reduction of serum lipids has been extensively investigated in both experimental and clinical trials (1). Statins are among the most widely used prescription drugs, and exert their lipid-lowering actions by reversible and competitive inhibition of the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), the rate-limiting step in the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, a precursor of cholesterol (2).…”

Section: Introductionmentioning

confidence: 99%

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Gonçalves

Calou

Siqueira

et al. 2011

Braz J Med Biol Res

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Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37% inhibition, respectively). Inhibitions of 20, 45 and 80% were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70%, respectively) and second phase (73, 57, and 66% inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86%, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.

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“…These conclusions resulted from the observation that the benefits provided by statins do not only depend on its LDL-lowering effect, but also on the impact of these drugs on organs, systems and morbid status, regardless of its original mechanism of action, which are properties called "pleotropic effects". These effects, promoted by several mechanisms, suggest the extended therapeutic action of statins, including: the anti-inflammatory power, as they reduce the plasma concentration of cytokines -tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6) -and positively act in situations with significant elevation of C-reactive protein (CRP) 1,3,[9][10][11][12][13][14][15][16][17][18][19][20] .…”

Section: Other Benefits Of Statins (Pleiotropy)mentioning

confidence: 99%

Can statins improve outcome in colorectal surgery?: Part I

Santos¹

2012

J. Coloproctol. (Rio J.)

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Statins are recommended for people who have high serum cholesterol, and this role of statins has been well documented. However, some activities of statins, independent of their lipid-lowering effect, in conditions such as systemic inflammatory response syndrome, nephropathy, and other anti-inflammatory activities that reduce proinflammatory cytokines, are called "pleiotropic" effects of statins. For this reason, many candidates for surgical treatment are users of statins. As a result, benefits are observed in these patients, such as minimized postoperative complications, especially in cardiac or coronary surgery. This study was designed with the purpose of determining the current status of the use of statins as an adjuvant in the prevention of postoperative complications in colorectal surgery. Ongoing studies and future researches will help clarify the potential impact of statins on the prophylaxis of postoperative complications.Keywords: statins; postoperative complications; colorectal surgery. RESUMO:As estatinas são drogas com o poder de inibir a hidroxi-metil-glutaril coenzima A redutase (HMG-CoA redutase), enzima que age na ativação da cadeia metabólica do colesterol. Portanto, sua principal ação, entre outros efeitos, é diminuir a concentração sérica total desse lipídeo. Por essa razão, muitas pessoas candidatas ao tratamento cirúrgico são pacientes usuários das estatinas. Seus outros efeitos, independente de sua capacidade para baixar os lipídeos circulantes, são denominados "efeitos pleiotrópicos" e estão, principalmente, relacionados à ação de bloqueio das atividades pró-inflamatórias, sobretudo minimizando, nos cardiopatas ou coronariopatas submetidos às operações cardíacas ou coronarianas, a prevalência da síndrome da reação inflamatória sistêmica, inclusive quando desencadeada por infecção. Estudos recentes têm sido elaborados para maiores conhecimentos dos mecanismos de ação das estatinas, especialmente em pacientes cardiopatas submetidos a tratamentos cirúrgicos não cardíacos ou em outros pacientes com o propósito de fazer a profilaxia das complicações pós-operatórias, inclusive as relacionadas diretamente com os agentes infecciosos. O presente manuscrito foi delineado com o objetivo de se conhecer a situação atual do uso das estatinas como adjuvante na prevenção das complicações pós-cirúrgicas em operações colorretais.Palavras-chave: estatinas; complicações pós-operatórias; cirurgias colorretais.

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Effects of statins beyond lipid lowering: Potential for clinical benefits

Cited by 112 publications

References 109 publications

Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway

Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Can statins improve outcome in colorectal surgery?: Part I

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