Simvastatin and Indomethacin Have Similar Anti‐Inflammatory Activity in a Rat Model of Acute Local Inflammation

Abstract

Statins, such as simvastatin, lower circulating cholesterol levels and are widely prescribed for the treatment of hypercholesterolaemia. Several studies have shown unexpected effects of statins on inflammation. We studied the anti-inflammatory effect of simvastatin using a standard model of an acute local inflammation, the carrageenan-induced footpad oedema. Experimental groups (n = 6 -8) were given simvastatin in a dose range 5-30 mg/kg, indomethacin 1-8 mg/kg and methylcellulose (control) per os . Footpad volume was measured with a plethysmograph and compared with the pre-injection volume of the same paw. Swelling (in microlitres) was then calculated, and in drug-treated animals, per cent inhibition was derived through comparison with the control group. Histopathological examination of the skin biopsies was performed to examine severity of paw skin lesions and to confirm the simvastatin-induced inhibition of acute inflammation. Both simvastatin and indomethacin administered orally, 1 hr before carrageenan injection, significantly reduced the extent of footpad oedema. Indomethacin dose-dependently blocked the swelling; the maximal effect was obtained with 8 mg/kg by 48.3% (P < 0.05). Simvastatin produced a comparable anti-inflammatory activity at a dose of 5 mg/kg (32%), while 10 and 30 mg/kg caused a 47.6% and 51.7% reduction, respectively, with the maximal effect observed at 20 mg/kg by 57.2% (P < 0.05). The comparison of the ED 50 of these agents on molar basis showed equipotent anti-inflammatory activity. Histopathological examination of the footpad skin biopsies revealed that simvastatin, dose-dependently and comparablly to indomethacin, reduced polymorphonuclear leucocyte infiltration. These data support the hypothesis that simvastatin has an acute anti-inflammatory activity.

Effects of local simvastatin–alendronate conjugate in preventing periodontitis bone loss

“…These findings were consistent with, and may partially explain, the preservation of interproximal bone volume and bone thickness in the SIM–ALN–CD/LPS group. These results were not unexpected because simvastatin previously has been shown to reduce inflammation and osteoclast numbers in rats. Alendronate has long been known to inhibit osteoclast activity in rats ; however, local alendronate may have little effect on osteoclast numbers and inflammation .…”

Protective Mechanisms of Simvastatin in Experimental Periodontal Disease

“…Prevalent hemodialysis patients under statins treatment presented significantly reduced MPO activity 35 . Nezić et al 36 observed that, at a dose range of 5 to 30 mg/kg, simvastatin reduced polymorphonuclear leukocyte infiltration in the carrageenan‐induced footpad edema model, dose dependently and comparably to indomethacin.…”

Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells’ Survival and Hindering Cytochrome C-Mediated Apoptosis

“…(0.25 LD 50 /kg). This experimental sepsis is a widely accepted model that is featured with high-grade acute systemic inflammation, inflammatory infiltration, increased oxidative stress, and apoptosis of organ tissues [ 14 , 38 , 39 ]. Simvastatin was administered in the three different dose regimens (10, 20, and 40 mg/kg p.o.…”

“…Numerous experimental studies demonstrated that statins, well-known lipid-lowering drugs, improved survival, and prevent tissue and organ injuries in local inflammation [ 14 ] or sepsis induced by LPS or CLP [ 15 , 16 ]. By inhibition of hydroxy-3-methylglutaryl-CoA (HMG-CoA), reductase statins block the mevalonate pathway and activation of intermediate products involved in cell signaling pathways, such as apoptosis or cell survival.…”