02 May 2003 : Case report
Effect of 5-aminoisoquinolinone, a water soluble, potent inhibitor of the activity of poly (ADP-ribose) polymerase, in a rodent model of lung injuryL. Dugo, S. Cuzzocrea, M. McDonald, E. Mazzon, I. Serraino, M. Threadgill, A. Caputi, C. Thiemermann
Med Sci Monit 2003; 9(1): 22- :: ID: 15069
Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation. Continuous or excessive activation of PARP produces extended chains of ADP-ribose on nuclear proteins and results in a substantial depletion of intracellular NAD+ and subsequently ATP, which may lead to cell death [1,2]. Production of reactive oxidants such as hydrogen peroxide, superoxide anions, hydrogen peroxide or hydroxyl radical at the site of inflammation contributes of tissue damage .The aim of the present study was to evaluate the effects of a novel and potent inhibitor of PARP activity, 5-Aminoisoquinolinone (5-AIQ), on neutrophil recruitment in the acute inflammation induced by zymosan-activated plasma in mice. Intra-thoracic administration of zymosan-activated plasma leads to an increase in neutrophil infiltration of the lung at 24hr. The potent PARP inhibitor 5-AIQ reduced the degree of lung injury and attenuated the expression of P-selectin and ICAM-1 as well as the recruitment of neutrophils into the lung during acute inflammation. The up-regulation/expression of P-selectin and ICAM-1 in human endothelial cells exposed to oxidative stress (peroxynitrite) or to a pro-inflammatory cytokine (tumor necrosis factor alpha, TNF-a) was also attenuated by 5-AIQ.These findings provide the first evidence that the activation of PARP participates in neutrophil-mediated lung injury by regulating the expression of P-selectin and ICAM-1.References: 1.Schraufstatter IU, Hinshaw DB, Hyslop PA, Spragg RG, Cochrane CG: J Clin Invest, 1986; 77: 1312-20 2.Thies RL, Autor AP: Arch Biochem Biophys, 1991; 286: 353-63 3.Cuzzocrea S, Costantino G, Mazzon E, Caputi AP: Br J Pharmacol, 1999; 126: 407-14
Keywords: 5-aminoisoquinolinone pleurisy, oxygen radicals, poly (ADP-ribose) synthetase, zymosan-activated plasma
01 June 2023 : EditorialEditorial: Infectious Disease Surveillance Using Artificial Intelligence (AI) and its Role in Epidemic and Pandemic Preparedness
Med Sci Monit 2023; 29:e941209
01 Jun 2023 : Clinical ResearchRoot Canal Numbers and Configurations in 1080 Permanent Canine Teeth in 270 Saudi Subjects Using Cone-Beam ...
Med Sci Monit In Press; DOI: 10.12659/MSM.940472
01 Jun 2023 : Clinical ResearchInternal Orifice Alloy Closure: A New Procedure for Treatment of Perianal Fistulizing Crohn’s Disease
Med Sci Monit In Press; DOI: 10.12659/MSM.940873
01 Jun 2023 : Clinical ResearchEffectiveness of Needle Aspiration versus Surgical Excision for Symptomatic Synovial Cysts of the Hip: A Si...
Med Sci Monit In Press; DOI: 10.12659/MSM.940187
01 Jun 2023 : Clinical ResearchInfluence of Insulin Resistance on Diabetes Nephropathy
Med Sci Monit In Press; DOI: 10.12659/MSM.939482
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
01 Jan 2022 : EditorialEditorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...
Med Sci Monit 2022; 28:e935952