Turk J Med Sci. 2015;45(1):18-26. doi: 10.3906/sag-1308-48.
BACKGROUND/AIM: 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.
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.
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).
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.
背景/目的：对乙酰氨基酚（APAP）过量会导致严重的肝损伤，进而可能发展为急性肝衰竭。最近的研究表明，抑制聚（ADP-核糖）聚合酶（PARP）可减少组织坏死和炎症。我们评估了 PARP 抑制剂 3-氨基苯甲酰胺（3-AB）在 APAP 诱导的肝毒性啮齿动物模型中的疗效。
24 只 Sprague-Dawley 大鼠平均分为 3 组：假手术组、APAP 组和 APAP+3-AB 组。在实验组中，APAP 经口给予 1 g/kg，在 APAP+3-AB 组中，APAP 处理后 1 小时内腹膜内给予 3-AB，剂量为 20mg/kg。初始 APAP 给药后 48 小时处死存活动物。采集血样和肝组织进行组织病理学和生化分析。
APAP+3-AB 治疗组的一组氧化应激参数，以及血清天冬氨酸氨基转移酶、丙氨酸氨基转移酶、新蝶呤、亚硝酸盐/硝酸盐和组织学损伤评分，与单独用 APAP 治疗的组相比显著降低（P<0.05，APAP 与 APAP+3-AB）。
本研究表明 3-AB 抑制 APAP 诱导的肝损伤并降低新蝶呤水平。本研究结果表明，PARP 抑制剂可能是一种有效的辅助治疗方法，可改善 APAP 诱导的肝毒性的结局。
