Прегледај по Аутор "Nežić, Lana"

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    Effect of simvastatin on proinflammatory cytokines production during lipopolysaccharide-induced inflammation in rats
    (Slovak Academy of Sciences, 2009) Nežić, Lana; Škrbić, Ranko; Dobrić, Silva; Stojiljković, Miloš P.; Šatara, Svjetlana S.; Milovanović, Zoran A.; Stojaković, Nataša
    The effect of simvastatin applied in a short-term pretreatment on proinflammatory cytokines production in acute systemic inflammation induced by endotoxin – lipopolysaccharide (LPS) in rats was investigated. Both LPS and simvastatin doses were established in separate experiments in which increasing doses of both compounds were given to obtain the LD50 LPS and the maximally protective dose of simvastatin against LD50 LPS. To determine the anti-inflammatory effect, simvastatin was given orally for 5 days, followed by a single intraperitoneal non-lethal dose of LPS (0.25 LD50). Plasma concentrations of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-6 were measured by enzyme-linked immunosorbent assay. The acute i.p. LD50 LPS amounted to 22.15 mg/kg. Simvastatin of 20 mg/kg p.o. was maximally protective against LD50 LPS, and this dose was used for studying its effects on LPS-induced cytokines production. Cytokines concentrations were significantly increased upon challenge of non-lethal dose of LPS. The peak levels of TNF-α and IL-1β were significantly suppressed by simvastatin, compared to control rats only treated with dimethylsulfoxide before LPS. In contrast, simvastatin did not affect IL-6 levels at all timepoints. Simvastatin pretreatment given orally produced acute anti-inflammatory effects by inhibiting TNF-α and IL-1β, but no IL-6 production.
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    Simvastatin and Indomethacin Have Similar Anti-Inflammatory Activity in a Rat Model of Acute Local Inflammation
    (Wiley, 2009) Nežić, Lana; Škrbić, Ranko; Dobrić, Silva; Stojiljković, Miloš P.; Jaćević, Vesna; Stoisavljević Šatara, Svjetlana; Milovanović, Zoran A.; Stojaković, Nataša
    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 ED50 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.