Department of Pharmacology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
Eur J Pharmacol. 2010 Feb 25;628(1-3):274-81. doi: 10.1016/j.ejphar.2009.11.027. Epub 2009 Nov 15.
Acetaminophen is one of the most popular analgesic and antipyretic drugs and its overdose, which can cause severe damage to liver and kidneys, is one of the most common reasons of emergency admissions. In this study we investigated the effects of curcumin, derived from plant Curcuma longa, on acetaminophen toxicity, and the possibility of combining therapy of curcumin and N-acetyl cysteine (NAC) to treat this toxicity. The experiments were conducted on 72 male Sprague-Dawley rats randomly divided into 12 groups. Control group was left without treatment, and the other groups were treated with different combinations of acetaminophen, curcumin and NAC. 15min after intraperitoneal injection, the blood level of curcumin was measured using HPLC. Blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), blood urea nitrogen and creatinine were determined 18 and 42h after acetaminophen injection. One week later, the left kidney and the caudate lobe of the liver were harvested to assay glutathione peroxidase, catalase and malondialdehyde. The right kidney and the remaining lobes of the liver were used for histopathology. Analysis of organ function and oxidation parameters showed that curcumin significantly reduced toxic effects of acetaminophen on the liver and kidneys in a dose-dependent manner and significantly potentiated the protective effects of NAC. These findings were confirmed by histopathology. It is concluded that curcumin can protect the liver and kidney from the damage caused by acetaminophen overdose. Moreover, curcumin has the potential to be used in a combination therapy with NAC, significantly decreasing the therapeutic dose of NAC and therefore its side-effects.
对乙酰氨基酚是最常用的解热镇痛药之一,其过量使用可导致肝肾功能严重损伤,是急诊入院最常见的原因之一。在这项研究中,我们研究了姜黄素(植物姜黄中的一种成分)对乙酰氨基酚毒性的影响,以及姜黄素和 N-乙酰半胱氨酸(NAC)联合治疗这种毒性的可能性。实验在 72 只雄性 Sprague-Dawley 大鼠上进行,随机分为 12 组。对照组不给予任何治疗,其他组给予不同剂量的对乙酰氨基酚、姜黄素和 NAC 联合治疗。腹腔注射 15min 后,采用 HPLC 法测定血中姜黄素浓度。注射对乙酰氨基酚后 18h 和 42h 测定血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、血尿素氮和肌酐水平。1 周后,取左肾和尾状叶肝脏进行谷胱甘肽过氧化物酶、过氧化氢酶和丙二醛测定,右肾和剩余肝叶用于组织病理学检查。器官功能和氧化参数分析表明,姜黄素可剂量依赖性地减轻对乙酰氨基酚对肝、肾的毒性作用,显著增强 NAC 的保护作用。组织病理学检查结果也证实了这一点。研究结果表明,姜黄素可保护肝、肾免受对乙酰氨基酚过量的损伤。此外,姜黄素与 NAC 联合应用具有潜力,可显著降低 NAC 的治疗剂量,从而减少其副作用。