Naslov
The protection of liver toxicity of acetaminophen by cAMP

Autori
Čulo, Filip ; Renić, Marija ; Aleksić, Joško ; Matić, Tomas

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Book of Abstracts of the 6th European Congress of Immunology / - Pariz : European Federation of Immunological Societes, 2006, 493-493

Skup
6th European Congress of Immunology

Mjesto i datum
Pariz, Francuska, 06.09.2006. - 09.09.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
IL-1alpha; acetaminophen; cAMP; rolipram; DDA; liver toxicity

Sažetak
It is known that proinflammatory cytokines influence the effect of hepatotoxic chemicals on liver (1). Previously we have shown that IL-1alpha and IL-6 have hepatoprotective effect if given to mice before administration of acetaminophen (APAP) and that this effect is partially mediated by PGE2 (1, 2). Since many inflammatory cytokines stimulate the synthesis of cAMP as well as PGE2, we investigated the effect of agonists, antagonists and inhibitors of cAMP degradation on APAP toxicity. APP (300 mg/kg) was administered intragastrically to mice which were given one to two hours before or up to 3 hours after a stable agonist of cAMP (dibutyryl-cAMP – Db-cAMP), antagonist (2, 3-dideoxyadenosine – DDA) or inhibitor of phoshodiesterase IV (Rolipram). All agents were given i.p. The survival of mice was followed for 72 hours and level of serum aminotransferases (AST and ALT) were determined 18-24 hours after administration of APAP. Db-cAMP (25 mg/kg) as well as Rolipram (8 mg/kg) significantly increased the survival of mice and reduced AST and ALT serum concentration if given 1-2 hours before or up to 2 hours after AAP administration. Db-cAMP had the same effect if given 3 hours after AAP, but effect was not statistically significant. On the contrary, DDA (160 microg/kg) decreased the survival of mice and increased serum aminotransferase concentration if given 2 hours before or ½ ; hours after AAP, but only effect on aminotransferase level was statistically significant. The treatment of animals with APAP greatly decreased the level of cAMP (20 or more times) in liver in vivo (the degradation of cAMP was blocked by rolipram). IL-1alpha, which was previously shown to have protective effect on APAP toxicity, if given before APAP, greatly increased the synthesis of cAMP in liver in vivo in comparison to saline control (to approximately 2/3 level in normal mice), and this effect could be blocked almost completely with DDA, given after IL-1α but before AAP. Presently, we are investigating signaling ways of this protective effect, using more specific inhibitors of cAMP or its downstream intracellular mediators.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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