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

Abstract

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.

Carrageenan‐induced inflammation promotes ROS generation and neutrophil extracellular trap formation in a mouse model of peritonitis

“…It has been previously shown that carrageenan is able to induce neutrophil migration in different animal models [14][15][16][17]21]. We first sought to characterize the effect of carrageenan on neutrophil migration to mice peritoneum.…”

Virtual Histology Evaluation of Atherosclerosis Regression During Atorvastatin and Ezetimibe Administration - HEAVEN Study -

“…27 HMG CoA inhibitors (ie, statins) decrease the level of TNF-α. 28, 29 The interplay between HMG CoA and TNF-α is interesting. It is known that TNF-α induces apoptosis via inhibition of HMG CoA and adding mevalonat to the cell culture inhibits this effect.…”

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

“…Statins are also known for their pleiotropic effects, which are independent of their lipidlowering properties. Among the effects of statins, the most relevant are anti atherosclerotic and antiinflammatory actions, improvement of endothelial dysfunction, anti-thrombosis and anti-oxidant actions, prevention of Alzheimer's disease and antineoplasic actions (Gonçalves et al, 2011). Although such clinical benefits are mediated in part through lipid modulation, recent studies demonstrate broader properties for statins, particularly in modifying inflammatory pathways ongoing within the atherosclerotic lesion (Ross, 1999).…”

“…This observation prompted subsequent in vitro studies that demonstrated that statins interfered with production of several important proinflammatory mediators (Pahan et al, 1997). Most of the reports point to the antiinflammatory effects of statins focused on cardiovascular diseases and atherosclerosis and about orally administration of these drugs (Garjani et al, 2008;Gonçalves et al, 2011;Kumar et al, 2010). Also studies showed that statins has a biphasic pro-and antiinflammatory effect (Garjani et al, 2008).…”