02 May 2003
Role of poly(ADP-ribose) polymerase (PARP) activation in the pathogenesis of toxic liver injury
J. Mabley, A. Salzman, C. SzaboMed Sci Monit 2003; 9(1): 37-0 :: ID: 15100
Abstract
Poly(ADP-ribose)polymerase (PARP) is a multifunctional nuclear enzyme, overactivation of which promotes inflammatory mediator expression and cell dysfunction. Acetaminophen (Tylenol) induces an acute liver toxicity followed by death via free radical and oxidant generation. We investigated whether a potent, novel inhibitor of PARP, INO-1001, can protect against acetaminophen induced liver damage. Treatment of male BALB/c mice with acetaminophen (350 mg/kg i.p.) results in 80% mortality at 24h. Simultaneous treatment with INO-1001 (10 or 30 mg/kg orally) reduced mortality to 10% and 0% respectively. Moreover, delaying the start of INO-1001 administration (10 or 30mg/kg orally) to 4h after acetaminophen administration still protects the mice reducing mortality to 15% and 30%, respectively. Analysis of serum and liver removed 8h after acetaminophen administration showed increased serum AST (from 132I14 to 2440I252 U/L) and liver MDA (from 1.9I0.1 to 4.4I0.3 nmol/mg protein). Simultaneous treatment with INO-1001 (10 or 30 mg/kg) decreased the serum AST to 572I88 and 438I78 U/L and the liver MDA to 2.2I0.4 and 2I0.2 nmol/mg protein respectively. In conclusion, PARP activation contributes to acetaminophen hepatotoxicity. References: 1.Virág L, Szabó C: The therapeutic potential of PARP inhibition. Pharmacological Reviews, 2002; 54: 375-429
Keywords: peroxynitrite, Liver, Hepatocytes, Acetaminophen
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
08 Mar 2024 : Clinical Research
Evaluation of Foot Structure in Preschool Children Based on Body MassMed Sci Monit In Press; DOI: 10.12659/MSM.943765
15 Apr 2024 : Laboratory Research
The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in OsteoarthritisMed Sci Monit In Press; DOI: 10.12659/MSM.943738
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
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 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952