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槲皮素降低了双氯芬酸在大鼠关节炎痛风疼痛模型中的镇痛效果。

Quercetin decreases the antinociceptive effect of diclofenac in an arthritic gout-pain model in rats.

机构信息

Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, México.

Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional (IPN), Ciudad de México, México.

出版信息

J Pharm Pharmacol. 2021 Sep 7;73(10):1310-1318. doi: 10.1093/jpp/rgab093.

Abstract

OBJECTIVE

To analyse the antinociceptive interaction between quercetin (QUER) and diclofenac (DIC) in experimental arthritic gout-pain.

METHODS

The antinociceptive effect of DIC and QUER alone and in combination were evaluated using an arthritic gout-pain model. Pain was induced through intra-articular administration of uric acid in the rats and the treatments were administered 2 h later. Additionally, the cyclooxygenase (COX) activity was determined in rats treated with DIC, QUER and their combination.

KEY FINDINGS

DIC induced a maximal effect of 69.7 ± 2.7% with 3.1 mg/kg; whereas QUER only produced 17.6 ± 2.6% with the maximal dose (316 mg/kg). Ten of twelve DIC + QUER combinations showed a lesser antinociceptive effect than DIC alone did (P < 0.05). Moreover, DIC reduced total-COX (70.4 ± 1.3 versus 52.4 ± 1.8 and 77.4 ± 9.0 versus 56.1 ± 1.3, P < 0.05) and COX-2 (60.1 ± 1.0 versus 42.4 ± 1.8 and 58.1 ± 2.4 versus 48.7 ± 1.3, P < 0.05) activity after 1 and 3 h, respectively. Nevertheless, only the COX-2 activity induced by DIC was prevented in the presence of QUER (63.2 ± 3.0 versus 60.1 ± 1.0 and 56.6 ± 1.3 versus 58.1 ± 2.4 at 1 and 3 h, respectively).

CONCLUSIONS

All these data demonstrated that the simultaneous administration of QUER + DIC produces an unfavorable interaction on the antinociceptive effect of DIC. Therefore, this combination might not be recommendable to relieve arthritic gout-pain.

摘要

目的

分析槲皮素(QUER)和双氯芬酸(DIC)在实验性痛风性关节炎疼痛中的抗伤害作用。

方法

采用痛风性关节炎模型评价 DIC 和 QUER 单独及联合应用的镇痛作用。尿酸关节内给药诱导疼痛,2 小时后给予治疗。此外,还测定了给予 DIC、QUER 及其联合用药的大鼠的环氧化酶(COX)活性。

主要发现

DIC 以 3.1mg/kg 诱导最大效应 69.7±2.7%;而 QUER 仅以最大剂量(316mg/kg)产生 17.6±2.6%。十二种 DIC+QUER 组合中的十种的镇痛作用小于 DIC 单独使用时的镇痛作用(P<0.05)。此外,DIC 在 1 和 3 小时时分别降低总 COX(70.4±1.3 比 52.4±1.8 和 77.4±9.0 比 56.1±1.3,P<0.05)和 COX-2(60.1±1.0 比 42.4±1.8 和 58.1±2.4 比 48.7±1.3,P<0.05)活性。然而,只有在 QUER 存在的情况下,DIC 诱导的 COX-2 活性才被阻止(1 和 3 小时时分别为 63.2±3.0 比 60.1±1.0 和 56.6±1.3 比 58.1±2.4)。

结论

所有这些数据表明,同时给予 QUER+DIC 对 DIC 的镇痛作用产生不利的相互作用。因此,这种联合用药可能不适合缓解痛风性关节炎疼痛。

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