The role of prostaglandins in acute hepatotoxicity (CROSBI ID 537559)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Ćavar, Ivan ; Renić, Marija ; Kelava, Tomislav ; Aleksić, Joško ; Čulo, Filip
engleski
The role of prostaglandins in acute hepatotoxicity
Previously we have shown that liver cells of mice intoxicated with high dose of acetaminophen (Paracetamol, APAP) synthesize increased quantities of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and thromboxane (TXA2). The aim of study was to determine which of these prostanoids contribute to defensive reaction of host to toxic effect of APAP (i.e. is hepatoprotective) and those which increase the toxic effect of APAP (i.e. is pathogenic). The toxicity of APAP was determined by observing the survival of mice given a lethal dose of APAP by gastric lavage and concentration of serum aminotransferases (AST and ALT) in mice given a sublethal dose of APAP. The concentration of particular prostanoid in body fluid of mice was modulated either by giving exogenously its stabile analog or giving specific anti-PG antibodies or inhibitors of specific receptors. In previous investigations we have shown that 16-16-dimethyl-PGE2 (a stable analogue of PGE2) had a strong protective effect if given to mice before or after APAP ; in contrast, application of specific anti- PGE2 antibodies increased toxic effect of APAP. Here we have shown that anti-TXB2 antibodies have opposite effect than anti-PGE2 antibodies, i.e., when given to APAP intoxicated mice, they decreased significantly serum AST and ALT levels. Recombinant TXB2 (0, 2 mg/kg) had no significant effect on AST and ALT levels in same mice. Presently we are testing the effect of various prostanoids agonists and antagonist on survival of intoxicated mice. The effect protective PG-s on synthesis of hepatotrophic cytokine, IL-6 and induction of Stat3 protein will also be tested.
prostaglandin; acetaminophen; hepatotoxicity
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Podaci o prilogu
30-x.
2007.
objavljeno
Podaci o matičnoj publikaciji
Annual Meeting of the Croatian Immunological Society. Rovinj , Book of Abstracts 2007
Podaci o skupu
Annual meeting of the Croatian Immunological Society 2007
poster
19.10.2007-21.10.2007
Rovinj, Hrvatska