Dose-response effect of L-citrulline on skeletal muscle damage after acute eccentric exercise: an in vivo study in mice

• Published in: PeerJ (San Francisco, CA) Vol. 11; p. e16684
• Main Authors: Ghozali, Dhoni Akbar, Doewes, Muchsin, Soetrisno, Soetrisno, Indarto, Dono, Ilyas, Muhana Fawwazy
• Format: Journal Article
• Language: English
• Published: United States PeerJ. Ltd 18.12.2023; PeerJ Inc
• Subjects: Biochemistry; Dose response; Eccentric exercise; Enzyme-linked immunosorbent assay; Ethylenediaminetetraacetic acid; Histology; L-citrulline; Muscles; NOX2; Rehabilitation; Skeletal muscle damage; Sports Injury; Sports Medicine; TNNI2; Canada; Indonesia; NF-κB; HSP-70; L-citrulline; Eccentric exercise; Skeletal muscle damage; Caspase 3; TNNI2; Dose response; IL-6; NOX2
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.16684

Eccentric exercise may trigger mechanical stress, resulting in muscle damage that may decrease athletic performance. L-citrulline potentially prevents skeletal muscle damage after acute eccentric exercise. This study aimed to assess the dose-response effect of L-citrulline as a preventive therapy for skeletal muscle damage in mice after acute eccentric exercise. This is a controlled laboratory study with a post-test-only design. Male mice (BALB/c,  = 25) were randomized into the following groups: a normal control (C1) (  = 5); a negative control (C2) with downhill running and placebo intervention (  = 5); treatment groups: T1 (  = 5), T2 (  = 5), and T3 (  = 5), were subjected to downhill running and 250, 500, and 1,000 mg/kg of L-citrulline, respectively, for seven days. Blood plasma was used to determine the levels of TNNI2 and gastrocnemius muscle tissue NOX2, IL-6, and caspase 3 using ELISA. NF-κB and HSP-70 expressions were determined by immunohistochemistry. Skeletal muscle damage (plasma TNNI2 levels) in mice after eccentric exercise was lower after 250 and 500 mg/kg of L-citrulline. Further, changes in oxidative stress markers, NOX2, were reduced after a 1,000 mg/kg dose. However, a lower level of change has been observed in levels of cellular response markers (NF-κB, HSP-70, IL-6, and caspase 3) after administration of L-citrulline doses of 250, 500, and 1,000 mg/kg. L-citrulline may prevent skeletal muscle damage in mice after acute eccentric exercise through antioxidant effects as well as inflammatory and apoptotic pathways. In relation to dose-related effects, it was found that L-citrulline doses of 250, 500, and 1,000 mg/kg significantly influenced the expression of NF-κB and HSP-70, as well as the levels of IL-6 and caspase 3. Meanwhile, only doses of 250 and 500 mg/kg had an impact on TNNI2 levels, and the 1,000 mg/kg dose affected NOX2 levels.