Turkish Journal of Medical Sciences
Abstract
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. Materials and 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). Conclusion: 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.
DOI
10.3906/sag-1308-48
Keywords
Acetaminophen, toxicity, PARP inhibition, neopterin, nitrosative stress, oxidative stress
First Page
18
Last Page
26
Recommended Citation
DÖNMEZ, M, UYSAL, B, POYRAZOĞLU, Y, ÖZTAŞ, Y. E, TÜRKER, T, KALDIRIM, Ü, & KORKMAZ, A (2015). PARP inhibition prevents acetaminophen-induced liver injury and increases survival rate in rats. Turkish Journal of Medical Sciences 45 (1): 18-26. https://doi.org/10.3906/sag-1308-48
