1H-NMR-Based Analysis for Exploring Knee Synovial Fluid Metabolite Changes after Local Cryotherapy in Knee Arthritis Patients

Abstract

Rehabilitation using cryotherapy has widely been used in inflammatory diseases to relieve pain and decrease the disease activity. The aim of this study was to explore the metabolite changes in inflammatory knee-joint synovial fluids following local cryotherapy treatment (ice or cold CO2). We used proton nuclear magnetic resonance (1H NMR) spectroscopy to assess the metabolite patterns in synovial fluid (SF) in patients with knee arthritis (n = 46) before (D0) and after (D1, 24 h later) two applications of local cryotherapy. Spectra from aqueous samples and organic extracts were obtained with an 11.75 Tesla spectrometer. The metabolite concentrations within the SF were compared between D1 and D0 using multiple comparisons with the application of a false discovery rate (FDR) adjusted at 10% for each metabolite. A total of 32 metabolites/chemical structures were identified including amino acids, organic acids, fatty acids or sugars. Pyruvate, alanine, citrate, threonine was significantly higher at D1 vs D0 (p < 0.05). Tyrosine concentration significantly decreases after cryotherapy application (p < 0.001). We did not observe any effect of gender and cooling technique on metabolite concentrations between D0 and D1 (p > 0.05). The present study provides new insight into a short-term effect of cold stimulus in synovial fluid from patients with knee arthritis. Our observations suggest that the increased level of metabolites involved in energy metabolism may explain the underlying molecular pathways that mediate the antioxidant and anti-inflammatory capacities of cryotherapy.

Effects of local cryotherapy on systemic endothelial activation, dysfunction, and vascular inflammation in adjuvant-induced arthritis (AIA) rats

“…When subchronically applied on inflamed joints, cryotherapy by itself exerted positive effects on disease activity, as demonstrated in patients with RA [12,33] and in AIA rats [13]. At the joint level, local cryotherapy decreased synovial Doppler hypersignal [34], IL-6, IL-17A, IL-1β but not TNF-α expression [13], and increased levels of metabolites of energy metabolism linked to antioxidant and anti-inflammatory activities [35]. The new finding of the present study is that local cryotherapy exerted positive effects remoted from the joint, improving all the aspects of AIA-induced systemic vascular pathology.…”

Pi-Dan-Jian-Qing Decoction Ameliorates Type 2 Diabetes Mellitus Through Regulating the Gut Microbiota and Serum Metabolism

“…Citric acid can be cleaved by ATP-citrate synthase (ACLY) to acetyl coenzyme A and oxaloacetate (OAA) ( Wang et al., 2021 ). Acetyl coenzyme A provides a basis for the synthesis of lipids, including arachidonic acid, which produces inflammatory mediators such as prostaglandins, leukotrienes, and thromboxanes ( Douzi et al., 2020 ). OAA is the second product of citric acid and can beconverted to malic acid, which is in turn oxidized by malic enzyme to pyruvic acid to form nicotinamide adenine dinucleotide phosphate (NADPH), which can produce ROS by the action of NADPH oxidase, and the excess ROS can lead to oxidative stress ( Munhoz et al., 2016 ).…”

Effect of Siphonochilus aethiopicus Methanolic Extract on Oxidative Stress Markers, Biochemical and Hematological Parameters in Experimentally Induced Arthritis Model in Mice

“…Phytotherapy is becoming increasingly popular in the modern world to address disease progression and extra-articular manifestations of rheumatoid arthritis due to cardiovascular complications, mood disorders, gastrointestinal and respiratory disorders, immunodeficiency, and blood disorders associated with various available rheumatoid arthritis therapies [12]. Among plants traditinally used in the treatment of inflammatory diseases in Cameroon, Siphonochilus aethiopicus is very much prized.…”