21 November 2002
The novel PARP inhibitor 5-aminoisoquinolinone reduces the liver injury caused by ischemia and reperfusion in the rat.
Helder Mota-Filipe, Bruno Sepodes, Michelle McDonald, Salvatore Cuzzocrea, Rui Pinto, Christoph ThiemermannMed Sci Monit 2002; 8(11): BR444-453 :: ID: 4846
Abstract
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.
Keywords: Immunohistochemistry, Intercellular Adhesion Molecule-1 - blood, Isoquinolines - pharmacology, L-Lactate Dehydrogenase - blood, Lipid Peroxidation, Lipid Peroxidation, Liver - drug effects, Liver - injuries, Liver - metabolism, Poly(ADP-ribose) Polymerases - antagonists & inhibitors, Rats, Time Factors, Transaminases - blood, gamma-Glutamyltransferase - blood
Editorial
01 February 2025 : Editorial
Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-SmokersDOI: 10.12659/MSM.948255
Med Sci Monit 2025; 31:e948255
In Press
Clinical Research
Correlation Descriptive Study on Nurses' Professional Values and Job Satisfaction and the Ethical Climate o...Med Sci Monit In Press; DOI: 10.12659/MSM.945639
Clinical Research
Pre- and Post-Surgical MRI Analysis of Levator Ani in Pelvic Organ Prolapse Patients: A Single-Center StudyMed Sci Monit In Press; DOI: 10.12659/MSM.945993
Clinical Research
Comparative Impact of Kinesio Taping and Post-Isometric Muscle Relaxation on Pain and Myofascial Mechanics ...Med Sci Monit In Press; DOI: 10.12659/MSM.945376
Clinical Research
Surgical Efficacy in Varicocele Ligation with Ephedrine-Assisted Blood Pressure ControlMed Sci Monit In Press; DOI: 10.12659/MSM.946234
Most Viewed Current Articles
17 Jan 2024 : Review article 6,968,210
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research 701,772
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Mar 2024 : Editorial 25,357
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...DOI :10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
28 Jan 2024 : Review article 19,972
A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and FutureDOI :10.12659/MSM.943912
Med Sci Monit 2024; 30:e943912