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吲哚美辛和环磷酰胺而非英夫利昔单抗对佐剂诱导性关节炎引起的肝脏代谢变化的保护作用。

Protective effects of indomethacin and cyclophosphamide but not of infliximab on liver metabolic changes caused by adjuvant-induced arthritis.

机构信息

Department of Pharmacy and Pharmacology, University of Maringá, Bloco K68-106, Avenida Colombo, 5790, CEP: 87020-900, Maringá, Paraná, Brazil.

出版信息

Inflammation. 2011 Dec;34(6):519-30. doi: 10.1007/s10753-010-9259-3.

Abstract

In the study, indomethacin, cyclophosphamide, and infliximab were administered to adjuvant-induced arthritic rats to determine if they were able to prevent the abnormalities caused by arthritis on hepatic metabolism. The drugs were administered to arthritic rats, and at the clinical onset of arthritis (day 14 after adjuvant injection), the livers were perfused to evaluate gluconeogenesis, ureagenesis, oxygen uptake, L: -lactate, pyruvate, and ammonia release from L: -alanine. The effects of the drugs on body weight gain and the signs of arthritis (paw edema, appearance of secondary lesions, and weights of lymphoid tissues) were also evaluated. Cyclophosphamide could completely prevent liver metabolic changes and the inflammatory response. Indomethacin restored ureagenesis, minimized the decrease in gluconeogenesis, and exerted a partially beneficial effect on inflammatory reactions. Infliximab did not improve arthritis-induced liver metabolic alterations or inflammatory responses. These results suggest the participation of prostaglandins, but not TNF-α, on arthritis-induced liver metabolic alterations.

摘要

在这项研究中,给佐剂诱导关节炎大鼠施用吲哚美辛、环磷酰胺和英夫利昔单抗,以确定它们是否能够预防关节炎对肝脏代谢造成的异常。在关节炎大鼠中给予这些药物,在关节炎的临床发病(佐剂注射后第 14 天)时,对肝脏进行灌流以评估糖异生、尿素生成、耗氧量、L:-乳酸、丙酮酸和从 L:-丙氨酸释放的氨。还评估了药物对体重增加和关节炎迹象(爪肿胀、继发性病变出现和淋巴组织重量)的影响。环磷酰胺可以完全预防肝脏代谢变化和炎症反应。吲哚美辛恢复了尿素生成,最大限度地减少了糖异生的减少,并对炎症反应产生了部分有益的影响。英夫利昔单抗不能改善关节炎引起的肝脏代谢改变或炎症反应。这些结果表明,前列腺素参与了关节炎引起的肝脏代谢改变,但 TNF-α 没有参与。

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