Effects of oral cystine and glutamine on exercise-induced changes in gastrointestinal permeability and damage markers in young men.

PURPOSE: Although acute prolonged strenuous exercise has been shown to increase markers of gastrointestinal permeability and damage, little is known regarding the efficacy of nutritional supplement interventions on the attenuation of exercise-induced gastrointestinal syndrome. This study addressed the effects of oral amino acid supplementation on markers of gastrointestinal permeability and damage in response to exercise. METHODS: Sixteen active men aged 22.7 ± 2.6 years (mean ± standard deviation) completed placebo or cystine and glutamine supplementation trials in random order. Participants received either a placebo or cystine and glutamine supplements, three times a day for 5 days, separated by a 2-week washout period. On day 6, participants took their designated supplements 30 min before running at a speed corresponding to 75% of maximal oxygen uptake for 1 h, followed by a 4-h rest period. Blood samples were collected pre-exercise, immediately post-exercise, 30 min post-exercise, and 1, 2 and 4 h post-exercise on day 6. The plasma lactulose to mannitol ratio (L:M) and plasma intestinal fatty acid-binding protein (I-FABP) were used as markers of gastrointestinal permeability and damage, respectively. RESULTS: Plasma L:M (linear mixed model, coefficient ± standard error: - 0.011 ± 0.004, P = 0.0090) and changes (i.e., from pre-exercise) in plasma I-FABP (linear mixed model, - 195.3 ± 65.7 coefficient ± standard error (pg/mL), P = 0.0035) were lower in the cystine and glutamine supplementation trial than in the placebo trial. CONCLUSION: Oral cystine and glutamine supplementation attenuated the markers of gastrointestinal permeability and damage after 1 h of strenuous running in young men. TRIAL REGISTRATION NUMBER: UMIN000026008. DATE OF REGISTRATION: 13 December 2018.

Reduced PDGF-AA in subchondral bone leads to articular cartilage degeneration after strenuous running.

To identify the effects of running on articular cartilage and subchondral bone remodeling, C57BL/6 mice were randomly divided into three groups: control, moderate-, and strenuous running. Magnetic resonance imaging showed bone marrow lesions in the knee subchondral bone in the strenuous-running group in contrast with the other two groups. The microcomputed tomography analysis showed promoted bone formation in the subchondral bone in mice subjected to strenuous running. Histological and immunohistochemistry results indicated that terminal differentiation of chondrocytes and degeneration of articular cartilage were enhanced but, synthesis of platelet-derived growth factor-AA (PDGF-AA) in the subchondral bone was suppressed after strenuous running. In vitro, excessive mechanical treatments suppressed the expression of PDGF-AA in osteoblasts, and the condition medium from mechanical-treated osteoblasts stimulated maturation and terminal differentiation of chondrocytes. These results indicate that strenuous running suppresses the synthesis of PDGF-AA in subchondral bone, leading to downregulated PDGF/Akt signal in articular cartilage and thus cartilage degeneration.

Strenuous running exacerbates knee cartilage erosion induced by low amount of mono-iodoacetate in rats.

BACKGROUND: It is still debated whether strenuous running in the inflammatory phase produces beneficial or harmful effect in rat knees. We examined (1) the dropout rate of rats during a 30-km running protocol, (2) influences of strenuous running and/or low amounts of mono-iodoacetate injection on cartilage, and (3) the effect of strenuous running on synovitis. METHODS: Rats were forced to run 30 km over 6 weeks and the dropout rate was examined. One week after 0.1 mg mono-iodoacetate was injected into the right knee, rats were forced to run either 15 km or not run at all over 3 weeks, after which knee cartilage was evaluated. Synovium at the infrapatellar fat pad was also examined histologically. RESULTS: Even though all 12 rats run up to 15 km, only 6 rats completed 30 km of running. Macroscopically, 0.1 mg mono-iodoacetate induced erosion at the tibial cartilage irrespective of 15 km of running. Histologically, 0.1 mg mono-iodoacetate induced loss of cartilage matrix in the tibial cartilage, and an additional 15 km of strenuous running significantly exacerbated the loss. Synovitis caused by mono-iodoacetate improved after running. CONCLUSIONS: Only 50% of rats completed 30 km of running because of foot problems. Strenuous running further exacerbated tibial cartilage erosion but did not influence synovitis induced by mono-iodoacetate.

Different responses of articular cartilage to strenuous running and joint immobilization.

OBJECTIVE: To compare the pathological changes in cartilage derived from rats that developed osteoarthritis either by joint immobilization or by strenuous treadmill running in order to better understand their respective pathomechanism. METHOD: A total of 24 male Wistar rats were randomly assigned to three groups: sedentary control (CON), immobilization (IM), and strenuous running (SR). For rats in the IM group, unilateral knee joint was immobilized in flexion. Rats in the SR group underwent treadmill running with high intensity. Eight weeks later, all animals were sacrificed. Femoral condyles were collected to take histological observation for cartilage characteristic and immunohistochemistry for collagen type II. In addition, cartilage samples were obtained to assess gene expression of aggrecan, collagen type II, biglycan, and fibromodulin by quantitative RT-PCR. RESULTS: Gross and histological observation showed osteoarthritic changes in groups SR and IM; however, more severe cartilage degradation was revealed in the latter. Proteoglycan and collagen II content decreased in groups SR and IM in comparison to group CON, with more loss in group IM. In group SR, mRNA levels in femoral cartilage were found to be unaltered for all the molecules measured. On the contrary, these molecules were significantly downregulated in group IM. CONCLUSION: Differences in gross observation, histological characteristics, and gene expression of proteoglycans and collagen II suggest that both knee immobilization and strenuous running would lead to degenerative change of cartilage, but at different stages of the degenerative process.