BACKGROUND: This study was designed to investigate the effects of 5-aminoisoquinolinone (5-AIQ), a water-soluble 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, gamma-glutamyl transferase, (ii). lipid peroxidation in liver tissue and (iii). by immunohistochemistry for PARP and intracellular adhesion molecule 1 (ICAM-1). RESULTS: 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 levels of transaminases, lactate dehydrogenase, and gamma-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 sections 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 clinical problem during shock, liver surgery, and liver transplantation.
BACKGROUND: This study was designed to investigate the effects of 5-aminoisoquinolinone (5-AIQ), a water-soluble 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, gamma-glutamyl transferase, (ii). lipid peroxidation in liver tissue and (iii). by immunohistochemistry for PARP and intracellular adhesion molecule 1 (ICAM-1). RESULTS: 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 levels of transaminases, lactate dehydrogenase, and gamma-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 sections 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 clinical problem during shock, liver surgery, and liver transplantation.
Authors: Salvatore Cuzzocrea; Emanuela Mazzon; Rosanna Di Paola; Tiziana Genovese; Nimesh S A Patel; Carmelo Muià; Michael D Threadgill; Angelina De Sarro; Christoph Thiemermann Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2004-11-18 Impact factor: 3.000
Authors: M Haddad; H Rhinn; C Bloquel; B Coqueran; C Szabó; M Plotkine; D Scherman; I Margaill Journal: Br J Pharmacol Date: 2006-07-24 Impact factor: 8.739
Authors: Rainer Kiefmann; Kai Heckel; Martina Doerger; Sonja Schenkat; Christian Kupatt; Mechthild Stoeckelhuber; Józefa Wesierska-Gadek; Alwin E Goetz Journal: Intensive Care Med Date: 2004-06-10 Impact factor: 17.440
Authors: Hai Huang; Gary W Nace; Kerry-Ann McDonald; Sheng Tai; John R Klune; Brian R Rosborough; Qing Ding; Patricia Loughran; Xiaorong Zhu; Donna Beer-Stolz; Eugene B Chang; Timothy Billiar; Allan Tsung Journal: Hepatology Date: 2014-04-01 Impact factor: 17.425