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异戊酸酯对瑞士小鼠氧化应激生物标志物和 GABA 能抗焦虑样特征的影响。

Effects of isopentyl ferulate on oxidative stress biomarkers and a possible GABAergic anxiolytic-like trait in Swiss mice.

机构信息

Postgraduate Program in Pharmacology, Federal University of Piauí, Teresina, Piauí, 64.049-550, Brazil.

Laboratory of Research in Experimental Neurochemistry of Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64.049-550, Brazil.

出版信息

Chem Biol Interact. 2018 Jun 1;289:119-128. doi: 10.1016/j.cbi.2018.03.009. Epub 2018 Mar 20.

Abstract

This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. In addition, the toxicity and antioxidant capacities were tested in Artemia salina and rat erythrocytes, respectively. The results suggest that, an acute administration of the IF at doses of 25, 50, 75 and 150 mg/kg (intraperitoneal, i.p.) significantly (p < 0.05) reduced the marble burying behavior of the animals as compared to the vehicle group, which demonstrates a calming effect of this chemical. It was observed that, the pre-treatment with flumazenil (2.5 mg/kg, i.p.), an antagonist of the gamma-amino butyrinc acid (GABA) receptor, significantly reversed the marble burying behavioral activity in the animals treated with the IF 150 mg/kg dose. Moreover, the reduction in nitrite content and lipid peroxidation levels, while an increased in the reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were also observed their hippocampus. Although, IF (2.36-14.16 mM) did not show toxicity in A. salina but exhibited a prominent antioxidant capacity in hydrogen peroxide-induced oxidative damage in rat erythrocytes. In conclusion, IF exhibited an anxiety-like effect in mice along with a potent antioxidant capacity, and we suppose it may have neuroprotective effects possibly via GABAergic transmission pathway.

摘要

本研究旨在评估异戊基阿魏酸(IF)的抗焦虑样作用及其可能的神经作用机制。为此,我们使用了瑞士白化小鼠的埋珠试验。测量了受试动物海马匀浆中涉及氧化应激的生物标志物。此外,分别在卤虫和大鼠红细胞中测试了毒性和抗氧化能力。结果表明,IF 在 25、50、75 和 150mg/kg(腹腔内,i.p.)剂量下的急性给药可显著(p<0.05)减少动物的埋珠行为,表明该化学物质具有镇静作用。观察到,用氟马西尼(2.5mg/kg,i.p.)预处理,GABA 受体拮抗剂,可显著逆转 IF 150mg/kg 剂量处理动物的埋珠行为活性。此外,还观察到其海马中的亚硝酸盐含量和脂质过氧化水平降低,而还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性增加。尽管 IF(2.36-14.16mM)在卤虫中没有显示出毒性,但在过氧化氢诱导的大鼠红细胞氧化损伤中表现出显著的抗氧化能力。总之,IF 在小鼠中表现出焦虑样作用,同时具有强大的抗氧化能力,我们推测它可能通过 GABA 能传递途径发挥神经保护作用。

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