title: PARP inhibition prevents acetaminophen-induced liver injury and increases survival rate in rats.
abstract: OBJECTIVE
  Acetaminophen (APAP) overdose results in severe liver damage that may develop into acute liver failure. Recent studies have demonstrated that inhibition of poly(ADP-ribose) polymerase (PARP) decreases tissue necrosis and inflammation. We evaluated the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, in a rodent model of APAP-induced hepatotoxicity.
  
  
  METHODS
  Twenty-four Sprague-Dawley rats were divided equally into 3 experimental groups: sham group, APAP group, and APAP + 3-AB group. In the experimental treatment groups APAP was administered orally at 1 g/kg and, in the APAP + 3-AB group, 3-AB was administered intraperitoneally at a dose of 20 mg/kg exactly 1 h after APAP treatment. Surviving animals were euthanized 48 h after initial APAP administration. Blood samples and liver tissues were collected for histopathological and biochemical analysis.
  
  
  RESULTS
  A panel of oxidative stress parameters, as well as serum aspartate aminotransferase, alanine aminotransferase, neopterin, and nitrite/nitrate and histological injury scores, were significantly reduced among the APAP + 3-AB treatment group relative to the group treated with APAP alone (P < 0.05, APAP vs. APAP + 3-AB).
  
  
  CONCLUSIONS
  The present study demonstrates that 3-AB inhibited APAP-induced hepatic injury and reduced neopterin levels. Results of the present study indicate that PARP inhibitors may be an effective adjuvant therapy resulting in improved outcomes in APAP-induced hepatotoxicity.
authors: Melahat
authors: M
authors: Dönmez
authors: Bülent
authors: B
authors: Uysal
authors: Yavuz
authors: Y
authors: Poyrazoğlu
authors: Yeşim E R
authors: YE
authors: Öztas
authors: Türker
authors: T
authors: Türker
authors: Ümit
authors: Ü
authors: Kaldirim
authors: Ahmet
authors: A
authors: Korkmaz
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D019798:Neopterin / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D020011:Protective Agents; D000082:Acetaminophen; D019798:Neopterin; C025160:3-aminobenzamide