Attoub Samir, Karam Sherif M, Nemmar Abderrahim, Arafat Kholoud, John Annie, Al-Dhaheri Wafa, Al Sultan Mahmood Ahmed, Raza Haider
Department of Pharmacology and Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
Cell Physiol Biochem. 2014;33(5):1400-10. doi: 10.1159/000358706. Epub 2014 May 5.
Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro.
Pistacia lentiscus oil (100µl) was administered orally into mice for 5 days.
Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant statistical difference when compared to control mice. Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia lentiscus oil when compared to the control group. Examination of gastrointestinal tissues sections revealed similar structural features with no difference in cell proliferation. In this context, pharmacological dilutions of Pistacia lentiscus oil (10(-6) - 10(-3)) did not affect the viability (cell death and proliferation) of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma cells HepG2. However, it appears that at the dose and time point studied, Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has specifically inhibited the activities and the expression of CYP2E1, CYP3A4, CYP1A1 and CYP1A2 differentially in different tissues. Our results also demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the GSH-dependent redox homoeostasis and detoxification mechanism in the tissues.
These data suggest a good safety profile of short term oral use of Pistacia lentiscus oil as a monotherapy in the treatment of various skin, respiratory, and gastrointestinal disorders. However, due to its inhibitory effect of various cytochrome P450s and mainly CYP3A4, this might have implications on the bioavailability and metabolism of drugs taken in combination with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil is intended to be uses in combination with other pharmacological agents in order to avoid potential drug-drug interaction leading to toxicity. This study will help in safer use of Pistacia lentiscus oil for therapeutic purpose.
乳香黄连木（漆树科）是一种开花植物，传统上用于治疗各种皮肤、呼吸道和胃肠道疾病。本研究的目的是评估乳香黄连木油在体内和体外是否具有任何短期毒性作用。
将乳香黄连木油（100µl）口服给予小鼠，持续5天。
体重测量未显示任何体重减轻。与对照小鼠相比，血清乳酸脱氢酶浓度未显示任何显著的统计学差异。同样，与对照组相比，血液、肾脏或肝脏功能测试表明乳香黄连木油无毒性。胃肠道组织切片检查显示结构特征相似，细胞增殖无差异。在此背景下，乳香黄连木油的药理稀释液（10⁻⁶ - 10⁻³）不影响小鼠胃干细胞、人结肠癌细胞HT29、人肝癌细胞HepG2的活力（细胞死亡和增殖）。然而，在所研究的剂量和时间点，乳香黄连木油处理似乎靶向了各种细胞色素P450，并在不同组织中差异地特异性抑制了CYP2E1、CYP3A4、CYP1A1和CYP1A2的活性和表达。我们的结果还表明，乳香黄连木油对组织中谷胱甘肽依赖性氧化还原稳态和解毒机制没有明显影响。
这些数据表明，短期口服乳香黄连木油作为单一疗法治疗各种皮肤、呼吸道和胃肠道疾病具有良好的安全性。然而，由于其对各种细胞色素P450，主要是CYP3A4的抑制作用，这可能会对与乳香黄连木油联合使用的药物的生物利用度和代谢产生影响。当乳香黄连木油打算与其他药物联合使用时，需要更多关注，以避免潜在的药物相互作用导致毒性。本研究将有助于更安全地将乳香黄连木油用于治疗目的。
Zotero 插件