Vliv nesteroidních protizánětlivých léčiv s různými mechanismy účinku na tělesnou teplotu a dráhu cyklooxygenázy kaskády kyseliny arachidonové na modelu akutního celkového ochlazení (vzduchová hypotermie) u potkanů
Authors:
Sergiy Shtrygol; Olga Tovchiga; Olesia Kudina; Olga Koiro; Tetiana Yudkevich; Tetiana Gorbach
Published in:
Čes. slov. Farm., 2022; 71, 214-223
Category:
Original Article
doi:
https://doi.org/https://doi.org/10.5817/CSF2022-5-214
Overview
NSAID jsou slibné látky pro prevenci poškození chladem (frigoprotektiva). Vliv profylaktického podávání neselektivního inhibitoru COX diklofenaku sodného (7 mg/kg) a vysoce selektivního inhibitoru COX-2 etorikoxibu (5 mg/kg) na biomarkery cyklooxygenázové dráhy byl studován na modelu akutního celkového ochlazení (vzduchová hypotermie při –18 °C po dobu 2 hodin). Diklofenak zcela zabránil poklesu tělesné teploty a předčil etorikoxib. V játrech potkanů byl bezprostředně po expozici chladu mírně zvýšen obsah COX-1, velmi výrazně obsah COX-2, snížena hladina PGE2 a zvýšeny hladiny PGF2α a zejména PGI2 a TXB2. V krevním séru byla hladina COX-1 snížena a změny hladin COX-2 a prostaglandinů byly podobné jako v játrech. Diklofenak působil mírně směrem k normalizaci obou izoforem COX v játrech, mírně zvyšoval obsah PGE2 a snižoval – PGF2α a TXB2, aniž by měnil hladinu PGI2. V séru diklofenak snížil hladinu COX-1 na podnormální hodnoty a jeho účinek na ostatní biomarkery byl podobný jako v játrech, s výjimkou mírného snížení PGI2. Diklofenak byl tedy horší než etorikoxib, který normalizoval COX-1, COX-2, PGE2, PGI2 v játrech, snížil obsah PGF2α a TXB2 v játrech na podnormální hodnoty, zatímco v krevním séru snížil COX-1, COX-2, PGE2 na podnormální hodnoty, normalizoval PGF2α a PGI2, významně snížil TXB2. Opačný stupeň intenzity vlivu diklofenaku a etorikoxibu na cyklooxygenázovou dráhu a tělesnou teplotu svědčí o disociaci protizánětlivé a frigoprotektivní aktivity. Inhibice oxidačního stresu není pro frigoprotektivní aktivitu NSAID rozhodující, protože diklofenak i přes slabší vliv na obsah 8-isoprostanu v játrech stále vykazuje maximální frigoprotektivní aktivitu.
Klíčová slova:
tělesná teplota – prevence poškození chladem – cyklooxygenáza – prostaglandiny – diklofenak sodná sůl – etorikoxib – frigoprotektivní aktivita
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