a School of Laboratory Medicine , Chengdu Medical College , Chengdu , Sichuan , PR China.
b Laboratory of Veterinary Drug Residue Prevention and Control Technology of Animal-derived Food , Chengdu Medical College , Chengdu , Sichuan , PR China.
Pharm Biol. 2018 Dec;56(1):337-343. doi: 10.1080/13880209.2018.1470191.
Citral is used as a potential natural treatment for various infectious diseases.
To examine the effect of citral on the mRNA expression and activities of cytochrome P450 (CYP450) enzymes and establish the relationship between citral-induced liver injury and oxidative stress.
ICR mice were randomly divided into citral (20, 200, and 2000 mg/kglow), Tween-80, and control groups (0.9% saline), 10 mice in each group. The citral-treated groups were intragastrically administered citral for 3 d, control groups treated with 0.5% Tween-80 and 0.9% saline in the same way. Liver injury and CYP450 enzymes were analyzed by analyzing the histopathological changes and the changes of related enzymes.
Citral treatment (2000 mg/kg) for 3 d increased serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels, as well as glutathione, gydroxyl radicals, malonaldehyde and total superoxide dismutase contents, but decreased the content of total antioxidant capacity. In doses of 20 and 200 mg/kg groups mice, the contents of NO were decreased significantly and other changes were similar to the 2000 mg/kg group mice, but the liver damage was most severe in the 2000 mg/kg group. Citral induced the mRNA expression and activities of CYP450 1A2, 2D22, and 2E1 in the liver of mice at doses of 20 and 200 mg/kg. There were no changes in testing indexes in Tween-80 treated group mice. Due to its toxic effects, the CYP induction effect of citral negatively correlated with its dose. Although the mRNA expression of CYP450 3A11 was induced by citral, its activity was not affected by low and moderate doses of citral. CYP450 3A11 activity was significantly decreased by high-dose citral.
Citral is hepatotoxic and induced oxidative stress in higher dose, which has a negative effect on CYP450 enzymes. These data suggest caution needs to be taken in order to avoid citral-drug interactions in human beings.
柠檬醛被用作治疗各种传染病的潜在天然药物。
研究柠檬醛对细胞色素 P450（CYP450）酶的 mRNA 表达和活性的影响，并建立柠檬醛诱导的肝损伤与氧化应激之间的关系。
ICR 小鼠随机分为柠檬醛（20、200 和 2000mg/kg 低剂量）、吐温-80 和对照组（0.9%生理盐水），每组 10 只。柠檬醛处理组连续 3 天经口给予柠檬醛，对照组以同样的方式给予 0.5%吐温-80 和 0.9%生理盐水。通过分析组织病理学变化和相关酶的变化来分析肝损伤和 CYP450 酶。
连续 3 天给予 2000mg/kg 剂量的柠檬醛可导致血清谷氨酸丙酮酸转氨酶和谷氨酸草酰乙酸转氨酶水平升高，以及谷胱甘肽、羟基自由基、丙二醛和总超氧化物歧化酶含量升高，但总抗氧化能力含量降低。在 20 和 200mg/kg 剂量组，NO 含量显著降低，其他变化与 2000mg/kg 剂量组相似，但以 2000mg/kg 剂量组的肝损伤最为严重。柠檬醛在 20 和 200mg/kg 剂量下诱导了小鼠肝脏 CYP450 1A2、2D22 和 2E1 的 mRNA 表达和活性。吐温-80 处理组小鼠的检测指标无变化。由于其毒性作用，柠檬醛的 CYP 诱导作用与其剂量呈负相关。虽然柠檬醛诱导了 CYP450 3A11 的 mRNA 表达，但它的活性不受低剂量和中剂量柠檬醛的影响。高剂量的柠檬醛显著降低了 CYP450 3A11 的活性。
柠檬醛在高剂量时具有肝毒性和诱导氧化应激作用，对 CYP450 酶有负面影响。这些数据表明，在人类中需要谨慎使用柠檬醛，以避免其与药物发生相互作用。
