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Tytuł oryginału:
The novel PARP inhibitor 5-aminoisoquinolinone reduces the liver injury caused by ischemia nad reperfusion in the rat.
Autorzy:
Mota-Filipe
Helder,
Sepodes
Bruno,
McDonald
Michelle,
Cuzzocrea
Salvatore,
Pinto
Rui,
Thiemermann
Christoph
Źródło:
Med. Sci. Monitor 2002: 8 (11) s.BR444-BR453, il., tab., bibliogr. 42 poz.
Sygnatura GBL:
313,278
Hasła klasyfikacyjne GBL:
farmacja
gastroenterologia
Typ dokumentu:
tytuł obcojęzyczny
praca doświadczalna
Wskaźnik treści:
zwierzęta
szczury
Streszczenie angielskie:
Background: This study was designed to investigate the effects of 5-aminoisoquinolinone (5 -AIQ), a watersoluble potent inhibitor of poly-(ADP-ribose) polymerase (PARP) in a rat model of liver ischemia-reperfusion injury. Material/Methods: Male Wistar rats were anesthetised with sodium pentobarbital (60 mg/kg, i.p.) and subjected to liver ischemia (for 30 minutes) and reperfusion (for 2 hours). Liver injury was assessed by measuring (i) the serum levels of transaminases, lactate dehydrogenase, ç-glutamyl transferase, (ii) lipid peroxidation in liver tissue and (iii) by immunohistochemistry for PARP and intracellular adhesion molecule 1 (ICAM-1). Resutls: Pre-treatment of rats (five minutes prior to onset of liver ischemia) with the PARP inhibitor 5-AIQ (3 mg/kg, i.v.) rather than vehicle reduced the rise in the serum levle sof transaminases, lactate dehydrogenase, and ç-glutamyl transferase as well as the degree of lipid peroxidation (measured as levels of malondialdehyde in the liver) caused by ischemia-reperfusion of the liver. Liver secitons obtained from 5-AIQ treated rats showed reduced PARP activation and less staining for ICAM-1. Conclusions: Taken together, these results show that 5-AIQ, a new water-soluble potent inhibitor of poly(ADP-ribose) polymerase, reduces the tissue injury associated with ischemia-reperfusion of the liver. we propose that 5-AIQ may be useful in the therapy conditions associated with ischemia-reperfusion of the liver which remains an important clincal problem during shock, liver surgery, and liver transplantation.
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