title: 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.
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Medical Faculty, University of Banja Luka, Banja Luka, Republic of Srpska, Bosnia and Herzegovina. lanaphare@yahoo.com
authors.forename: Lana
authors.initials: L
authors.lastname: Nezić
authors.forename: Ranko
authors.initials: R
authors.lastname: Skrbić
authors.forename: Silva
authors.initials: S
authors.lastname: Dobrić
authors.forename: Milos P
authors.initials: MP
authors.lastname: Stojiljković
authors.forename: Vesna
authors.initials: V
authors.lastname: Jaćević
authors.forename: Svjetlana Stoisavljević
authors.initials: SS
authors.lastname: Satara
authors.forename: Zoran A
authors.initials: ZA
authors.lastname: Milovanović
authors.forename: Natasa
authors.initials: N
authors.lastname: Stojaković
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D002351:Carrageenan; D019821:Simvastatin; D007213:Indomethacin