Anti-inflammatory and antioxidative effects of essential oil of Hyptis crenata on the intestinal injuries induced by methotrexate

Yuri de Abreu Gomes-Vasconcelos , Pedro Lucas Martins-Santiago , Dalgimar Beserra de Menezes , José Lima de Carvalho Rocha , Rutyleia Alves-Soares , Maria Diana Moreira-Gomes , Francisco Walber Ferreira-da-Silva , Kerly Shamyra da Silva-Alves , José Henrique Leal-Cardoso , Andrelina Noronha Coelho-de-Souza
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Abstract

Methotrexate (MTX) is an important drug for the treatment of cancer and other diseases. However, it induces many gastrointestinal inflammation-related side effects. The essential oil of Hyptis crenata (EOHc) has gastrointestinal protective and anti-inflammatory properties. Therefore, we aimed to investigate the effect of EOHc on MTX-induced intestinal inflammation in rats. Male Wistar rats were administered MTX or Saline for 3 days and EOHc (300 mg/kg) or vehicle for an additional 3 or 7 days. Half of the animal was euthanized 3 days after the end of MTX treatment (inflammation phase) and the remaining half euthanized 4 days later (post-inflammation phase). The MPO levels in the mucositis inflammation-related phase of the MTX-treated group were 284 % of the control in the duodenum (cont: 50,9 ± 9,97 U/mg of protein) and 231 % of the control in the ileum (cont: 30,4 ± 6,60 U/mg of protein). In the EOHc group, the levels were 50 % of control in the duodenum and 113 % in the ileum. During this phase, EOHc prevented the increase in TBARs levels and the decrease in thiol levels in the duodenum and jejunum. In the post-inflammation phase of mucositis, EOHc prevented the gastrointestinal transit alteration and, in general, increased food and water consumption. In conclusion, the observed effects, particularly the anti-inflammatory and antioxidant effects of EOHc, as well as its previously reported low toxicity, position EOHc as a promising candidate for reducing gastrointestinal side effects associated with the use of MTX.
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百里香精油对甲氨蝶呤引起的肠道损伤的抗炎和抗氧化作用
甲氨蝶呤(MTX)是治疗癌症和其他疾病的重要药物。然而,它会诱发许多与胃肠道炎症有关的副作用。百里香精油(EOHc)具有胃肠道保护和抗炎特性。因此,我们旨在研究 EOHc 对 MTX 诱导的大鼠肠道炎症的影响。雄性 Wistar 大鼠先服用 MTX 或生理盐水 3 天,然后再服用 EOHc(300 毫克/千克)或药物 3 天或 7 天。一半动物在 MTX 治疗结束 3 天后(炎症期)安乐死,另一半在 4 天后(炎症后期)安乐死。在粘膜炎炎症相关阶段,MTX 治疗组十二指肠的 MPO 水平是对照组的 284%(对照组:50.9 ± 9.97 U/mg 蛋白),回肠的 MPO 水平是对照组的 231%(对照组:30.4 ± 6.60 U/mg 蛋白)。在 EOHc 组,十二指肠和回肠中的蛋白质水平分别为对照组的 50% 和 113%。在这一阶段,EOHc 阻止了十二指肠和空肠中 TBARs 水平的升高和硫醇水平的降低。在粘膜炎的炎症后阶段,EOHc 可防止胃肠道转运功能的改变,并在总体上增加食物和水的消耗量。总之,观察到的效果,特别是 EOHc 的抗炎和抗氧化作用,以及之前报告的低毒性,使 EOHc 成为减少与使用 MTX 相关的胃肠道副作用的一种有前途的候选药物。
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