Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

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 Thiemermann

Med 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: Cells, Cultured, 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, Rats, Wistar, Reperfusion Injury, Time Factors, Transaminases - blood, gamma-Glutamyltransferase - blood

0 Comments

Editorial

01 August 2022 : Editorial  

Editorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937927

Med Sci Monit 2022; 28:e937927

In Press

10 Aug 2022 : Review article  

Programmed Cell Death in Diabetic Nephropathy: A Review of Apoptosis, Autophagy, and Necroptosis

Med Sci Monit In Press; DOI: 10.12659/MSM.937766  

10 Aug 2022 : Database Analysis  

Use and Effects of Augmentation of Labor with Oxytocin: A Single-Center, Retrospective, Case-Control Study ...

Med Sci Monit In Press; DOI: 10.12659/MSM.937557  

08 Aug 2022 : Clinical Research  

A 3-Year Clinical Evaluation of Endodontically Treated Posterior Teeth Restored with Resin Nanoceramic Comp...

Med Sci Monit In Press; DOI: 10.12659/MSM.937331  

08 Aug 2022 : Clinical Research  

Hemoglobin/Red Blood Cell Distribution Width Ratio in Peripheral Blood Is Positively Associated with Progno...

Med Sci Monit In Press; DOI: 10.12659/MSM.937146  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750