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

Dantas, Anna Carolina Batista; Batista-Júnior, Francisco Fábio de Araújo; Macedo, Larissa Freitas; Mendes, Mariana Noronha Castro; Azevedo, Ítalo Medeiros; Medeiros, Aldo Cunha

doi:10.1590/s0102-86502010000100011

Cited by 37 publications

(21 citation statements)

References 26 publications

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“…The present results indicate that lovastatin has a potent anti-inflammatory activity since it inhibits carrageenan-induced peritonitis and paw edema. Although these findings are consistent with studies showing these effects of statins in many inflammation models, most of them were carried out with other statins, mainly simvastatin (21)(22)(23).…”

Section: Discussionsupporting

confidence: 89%

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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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Section: Discussionsupporting

confidence: 89%

“…Lovastatin inhibited MPO release in a concentration-dependent manner by 23,79, and 86% at the three concentrations tested, respectively. Indomethacin (35.7 µg/mL) used as a positive control inhibited MPO release by 93%.…”

Section: Effects Of Lovastatin On the Release Of Human Neutrophil Mpomentioning

confidence: 90%

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

View full text Add to dashboard Cite

show abstract

“…Studies showed that lovastatin has a potent anti-inflammatory activity since it inhibits carrageenan-induced peritonitis and paw edema. Although these findings are consistent with studies showing these effects of statins in many inflammation models, most of them were carried out with other statins, mainly simvastatin (Dantas et al, 2010;Massaro et al, 2010;. Studies demonstrate that simvastatin provides a highly effective therapy in treating murine Collagen-Induced Arthritis (CIA), a surrogate model for human Rheumatoid Arthritis (RA).…”

Section: Discussionsupporting

confidence: 78%

Effect of Intraperitoneally Injection of Different Doses of Lovastatin on Pain and Inflammatory Response Induced by Formalin in Mice

Mirhadi¹

2011

American Journal of Animal and Veterinary Sciences

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Problem statement:The 3-Hydroxy-3-Methyl Glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have been unequivocally shown to reduce cardiovascular morbidity and mortality. Their lipid-lowering actions are by reversible and competitive inhibition of the enzyme HMG-CoA reductase, a precursor of cholesterol. It has been suggested that statins appear to have therapeutic benefits in diseases that are unrelated to elevated serum cholesterol levels, such as pain and inflammatory. The aim of this study was to determination the effect of intraperitoneally injection of different doses of lovastatin on pain and inflammatory response induced by formalin in mice. Approach: Mice were divided into 9 groups randomly: the first group received saline normal (ip) (saline group); the second group received Carboxymethylcellulose (CMC) 0.5% (ip) (vehicle group) and the next groups received respectively different doses of lovastatin (1, 5, 10, 20, 40, 80 and 100 mg kg daily −1 ) for 4 days (ip) before formalin test. After intrapawly injection of formalin, the time of hind paw biting and licking time measured in 5 min interval for an hour. Results: Results showed that formalin induces biphasic pain response (the first phase: 0-5 min and the second phase 15-40 min after injection). Intraperitoneal injection of lovastatin showed significant (p<0.05) decrease of pain responses in the first and the second phase in a dose dependently manner. Conclusion: According to our results, lovastatin has analgesic and anti-inflammatory effects on mice. Nevertheless, new studies must be carried out in order to determine the beneficial effects of statins in treatment of pain and inflammatory.

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“…Hajipour et al (2009) showed that Simvastatin pretreatment reduced intestinal I/R injury and was associated with downregulation of serum TNF- α and tissue malondialdehyde level and Simvastatin administration maintained cellular antioxidant enzyme contents compared to the I/R group after 3-hour reperfusion time [26]. Dantas et al (2010) found that Simvastatin pretreatment attenuated cyclophosphamide-induced urothelium inflammation in an experimental rat model, through significantly reducing plasma level of proinflammatory cytokines (TNF- α , IL-6, and IL-1 β ) [27]. …”

Section: Discussionmentioning

confidence: 99%

Antiapoptotic Effect of Simvastatin Ameliorates Myocardial Ischemia/Reperfusion Injury

et al. 2013

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Background. Myocardial ischemial reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty, and coronary bypass surgery. Injury of myocardium due to ischemial reperfusion includes cardiac contractile dysfunction, arrhythmias, and irreversible myocytes damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. Objective. This study was undertaken to investigate the potential role of Simvastatin in the amelioration of myocardial I/R injury induced by ligation of coronary artery in a rat model. Materials and Methods. Adult male Swiss Albino rats were randomized into 4 equal groups. Group (1): sham group: rats underwent the same anesthetic and surgical procedures as those in the control group except ligation of LAD coronary artery, group (2): control group: rats were subjected to regional ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary artery, group (3): control vehicle group: rats received vehicle of Simvastatin (normal saline) via IP injection and were subjected to regional ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary artery, group (4): Simvastatin treated group: rats were pretreated with Simvastatin 1 mg/kg i.p. 1 hr before ligation of LAD coronary artery. At the end of experiment (2 hr of reperfusion), blood samples were collected from the heart for the measurement of plasma level of cardiac troponin I (cTnI). After that the heart was harvested and divided into 3 parts; one part was used for measurement of apoptosis, another part was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α, and the last part for histopathology study. Results. Compared with the sham group, levels of myocardial TNF-α and IL-1β, IL-6, MCP-1, and MIP-1α and plasma cTnI were increased (P < 0.05). Histologically, all rats in control group showed significant (P < 0.05) cardiac injury. Furthermore, all rats in control group showed significant (P < 0.05) apoptosis. Simvastatin significantly counteracted the increase in myocardium level of TNF-α, IL-1B, IL-6, MCP-1 and MIP-1α, plasma cTnI, and apoptosis (P < 0.05). Histological analysis revealed that Simvastatin markedly reduced (P < 0.05) the severity of heart injury in the rats that underwent LAD ligation procedure. Conclusions. The results of the present study reveal that Simvastatin may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions and apoptosis which were induced by I/R injury.

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

Cited by 37 publications

References 26 publications

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

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

Effect of Intraperitoneally Injection of Different Doses of Lovastatin on Pain and Inflammatory Response Induced by Formalin in Mice

Antiapoptotic Effect of Simvastatin Ameliorates Myocardial Ischemia/Reperfusion Injury

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