COX-2/PGI2 pathway is involved in neuroprotection induced by N1-methylnicotinamide in hypoxia/ischemia of newborn rats

• Autorzy: Slomka M. , Ziembowicz A. , Lazarewicz J.W.
• Języki publikacji: EN

Abstrakty

EN

1-Methylnicotinamide (MNA) is a key metabolite of nicotinamide, which is an important cofactor in many metabolic pathways with intrinsic cytoprotective properties. Recent studies demonstrated that MNA induces in the periphery the anti-inflammatory and vasoprotective effects mediated by the COX-2/ PGI2 signaling pathway. The role of this pathway in the protection against ischemic injury has been emphasized by the increased risk of myocardial infarction, stroke or susceptibility to excitotoxic insults caused by COX-2 inhibitors. This suggests that administration of MNA resulting in activation of COX-2/PGI2 might provide neuroprotection in brain ischemia. The aim of this study was to evaluate neuroprotective abilities of MNA in the model of brain hypoxia/ischemia (HI) in 7-day old rat pups, and to assess its effects on COX-2 activity and eicosanoid levels in the ischemic brain. The results demonstrated that i.p. administration of 62.5 mg/kg MNA 30 min after HI induced a significant neuroprotection and a marked increase in COX-2 activity 6 and 24 h after the insult. This effect was not accompanied by changes in the COX-2 protein level, as measured with Western blotting. The analysis of the level of eicosanoids: 6-keto-PGF1alpha-a which is a stabile metabolite of PGI2, PGE2, and TXB2 in brain of rats treated with MNA after HI demonstrated in the ipsilateral cortex a significant increase in 6-keto-PGF1alpha 30 min after the treatment, while PGE2 and TXB2 levels did not change. Pretreatment with rofecoxib (COX-2 inhibitor) or indomethacin (unselective COX inhibitor) decreased the level of 6-keto-PGF1alpha in the ipsilateral cortex to values observed in the untreated ischemic brain. To test the hypothesis that neuroprotection evoked by MNA in HI model depends on activation of prostacylin receptors, the selective antagonist of these receptors RO 324479 was applied. However, pretreatment of rat pups subjected to HI with RO 324479 (10 mg/ kg i.p.) did not influence significantly the neuroprotective effect of MNA. Further studies are needed to assess the role of COX-2/PGI2 in the MNA-evoked neuroprotection.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.153

Twórcy

autor

Slomka M.

• Mossakowski Medical Research Centre, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland

autor

Ziembowicz A.

• Mossakowski Medical Research Centre, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland

autor

Lazarewicz J.W.

• Mossakowski Medical Research Centre, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland