Romanian Society of Pharmaceutical Sciences
 

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FISH-OIL PRECONDITIONING MODULATES PLASMA MCP-1 AND TIMP-1 LEVELS AFTER EXPERIMENTAL INDUCED TRANSIENT CEREBRAL ISCHEMIA

ADINA HUȚANU 1,2, EMOKE HORVATH 3, ALEX ORĂDAN 4, SEPTIMIU VOIDĂZAN 5, LIVIU CHIRIAC 6, DANIELA LUCIA MUNTEAN 7*, MINODORA DOBREANU 1,2

1.University of Medicine and Pharmacy of Târgu Mureș, Târgu Mureș, Romania
2 .Center for Advanced Medical and Pharmaceutical Research Târgu Mureș, Târgu Mureș, Romania
3 .Pathology Department, University of Medicine and Pharmacy, Târgu Mureș, Romania
4 .“Iuliu Hațieganu” University of Medicine and Pharmacy, Center for Animal Facility, Cluj-Napoca, Romania,
5 .Department of Epidemiology, University of Medicine and Pharmacy Târgu Mureș, Romania
6 .National Magnetic Resonance Center, Faculty of Physics, Babeș-Bolyai University, Cluj-Napoca, Romania
7 .Department of Analytical Chemistry and Drug Analysis, University of Medicine and Pharmacy, Târgu Mureș, Romania

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The aim of the study was to assess the dynamic changes in cytokines profile and their correlation to immunohistochemistry brain modifications after transient middle cerebral artery occlusion (tMCAO) in saline-treated ischemic rats compared to fish oil preconditioned rats. 30 Wistar male adult rats randomly divided into sham (n = 10), ischemic (n = 10), and fish oil (FO) (n = 10) groups underwent tMCAO using a silicone monofilament technique with a minimum invasive procedure. Blood was withdrawn at 6 hrs and 24 hrs after reperfusion, and ischemia was verified 24 hrs after reperfusion by MRI (magnetic resonance imaging) acquisition. Neurological assessment was performed using a five-point scale. Five cytokines (TNF-alfa, IL6, TIMP-1, MCP-1, and VEGF) were simultaneously analysed using the multiplex immunoassay based on xMAP (multi-analyte profiling) technology. Plasma concentration of TIMP-1 was higher in ischemic and FO group compared to sham, 6 hrs after reperfusion; in the ischemic group, the concentration of TIMP-1 raised significantly at 24 hrs (37.28 ± 4.85 pg/mL) compared to FO group (14.11 ± 1.79 ng/mL), p < 0.0001. Plasma MCP-1 concentration did not differ between sham (0.69 ± 0.18 pg/mL) and FO group (0.798 ± 0.060 pg/mL), while in the ischemic group level was significantly higher (1.627 ± 0.19 pg/mL), p = 0.0001. Whilst in the ischemic group, concentrations were elevated at both points of measurement, in the FO group the level significantly decreased after 24 hrs (p = 0.0005). Omega 3 PUFA (polyunsaturated fatty acid) decreased plasma MCP-1 level, a key cytokine involved in the inflammatory cell migration. Additionally, in Omega 3 preconditioned group, TIMP-1 expression was lower, probably due to a lower activation of matrix metalloproteinases.