The role of leukotriene inhibition using a 5-lipoxygenase (5-LO) inhibitor in a joint contracture model

Journal of Experimental Orthopaedics

Original Paper

David Berkoff¹  Alexander D. Jeffs¹  Michael Boyd²  Alexander Bassil³  Matthew Shelton⁴  Landon Larabee⁴  Ross Taylor⁵ 

[1] Department of Orthopaedics, The University of North Carolina, Chapel Hill, NC, USA;Department of Orthopaedics, The University of North Carolina, Chapel Hill, NC, USA;Department of Family Medicine, The University of North Carolina, Chapel Hill, NC, USA;Duke University School of Medicine, Durham, NC, USA;The University of North Carolina School of Medicine, Chapel Hill, NC, USA;Wake Forest University School of Medicine, Winston Salem, NC, USA;

关键词: Arthrofibrosis;    Leukotriene;    Contracture;    Caffeic Acid;    And 5-Lipoxygenase;   

DOI  :  10.1186/s40634-023-00616-w

 received in 2022-12-18, accepted in 2023-05-05,  发布年份 2023

来源: Springer

【 摘 要 】

PurposeArthrofibrosis is a common inflammatory complication of joint trauma and surgery. 5lipoxygenase (5-LO) is a key enzyme involved in inflammation. Inhibition of 5-LO has been shown to reduce inflammation in heart and lung models but has not been examined in a joint contracture model.MethodsTwenty-six rats underwent joint contracture. Six rats served as non-surgical controls. A 5-LO inhibitor, caffeic acid (CA), suspended in 10% ethanol was orally administered to 14 rats and ethanol without CA to the remaining 12 rats daily for 21 days. Leukotriene B4 (LTB4) levels were measured, both systemically and locally. 5-LO levels in the posterior capsule were quantified by measuring the ratio of the length of the posterior capsule demonstrating 5-LO immunostaining to the total length of the capsule.ResultsJoint contracture was successfully achieved in all rats who underwent manipulation. Levels of 5- LO measured in the posterior capsule were significantly increased in the animals who underwent surgery (56%/44–64) compared to the non-surgical control animals (7%/4–9). LTB4 levels were found to be significantly lower in the non-surgical control animals (107.79 ± 34.08 pg/ml) compared to all surgical animals (157.6 ± 55.3 pg/ml).ConclusionSurgical intervention resulted in increased 5-LO activity of the synovial surface of the posterior capsule and increased LTB4 levels in the patellar tendon—fat pad. Oral administration of the 5LO inhibitor, CA, was ineffective at reducing systemic and local LTB4 levels and preventing knee joint contracture. Inhibiting 5-LO activity may still be effective in preventing arthrofibrosis and warrants further investigation.

【 授权许可】

CC BY   
© The Author(s) 2023

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