Exhaustive Exercise Group Research Articles

Impact of ginger supplementation on serum PGE2, COX2, and IL-6 in response to exhaustive exercise in female taekwondo athletes

Abstract Inflammation and muscle soreness sometimes occur after high-intensity exercise in some athletes. This study aimed to determine the effect of a ginger supplement period on serum cyclooxygenase-2 (COX2), prostaglandin E2 (PGE2), and interleukin (IL)-6 in response to exhaustive exercise in female taekwondo athletes. In this semi-experimental study, 24 semi-professional female taekwondo athletes (mean age 19.75 ± 2.03 years, height 160 ± 6 cm, weight 53.99 ± 7.49 kg) were selected voluntarily. Subjects were randomly assigned to the ginger supplement + exhaustive (GE + EE) and exhaustive exercise (EE) groups. 24 doses of 2,000 mg of pure ginger supplement (3 days/week for 8 weeks) were taken in the morning and evening (4 capsules of 500 mg: 2 in the morning and 2 in the evening). Then Bruce’s test was performed as an exhaustive exercise. Blood samples were collected in two stages before and after the intervention, and serum levels of COX2, PGE2, and IL-6 were measured using the Elisa method. T-tests and analysis of variance with repeated measures were used to examine intra-group changes and compare between groups from pre-test to post-test using SPSS version 25 software. The results showed a significant increase in the level of serum COX2 (), and no significant increase in the level of serum PGE2 () and IL-6 () in the EE group compared to baseline levels. Also, there was a significant decrease in the level of serum PGE2 (), COX2 (), and IL-6 () in the group of GE + EE compared to baseline levels. In addition, there was a significant difference between the group of GE + EE and the EE (). GE + EE group, in comparison with the EE group, partially reduced inflammation. Taking 8-weeks of ginger supplementations can effectively reduce muscle inflammation following exhaustive exercise in female taekwondo athletes.

High-intensity interval training alleviates exhaustive exercise-induced HSP70-assisted selective autophagy in skeletal muscle

This study was designed to probe the effect of chaperone-assisted selective autophagy (CASA) on the maintenance of proteostasis during exhaustive exercise and uncover the alteration of CASA in muscle fibers with pre-high-intensity interval training (HIIT) intervention-induced muscle adaptation in response to exhaustive exercise. Rats were randomly divided into a control group; an exhaustive exercise group; and an HIIT + exhaustive exercise group. Results show myofibril damage and BiP levels were increased after exhaustive exercise, and the levels of the HSP70, BAG3, ubiquitin, autophagy-related proteins, and their interactions were increased. HIIT intervention before exhaustive exercise could decrease myofibril injury and BiP levels, accompanied by down-regulation of HSP70/BAG3 complex and selective autophagy. In conclusion, exhaustive exercise promotes CASA to clear protein aggregation for keeping proteostasis in muscle fibers; pre-HIIT intervention improves myofibril injury and unfold protein response caused by exhaustive exercise, which might contribute to inhibit the augmentation of CASA.

The effects of subtoxic dose of acetaminophen combined with exercise on the liver of rats.

Regular physical exercise is beneficial to the body. Acute exercise causes oxidant stress in many tissues including the liver by creating an unbalanced status between oxidant and antioxidant levels. Analgesic drugs are commonly consumed to reduce the pain after exercise. Acetaminophen (APAP), commonly used as an over-the-counter analgesic, can cause hepatotoxicity. The aim of this study was to investigate the effect and underlying mechanisms of APAP at subtoxic dose, which is given after the acute and exhaustive exercise on the rat livers. Male Wistar rats weighing 200-250 g were divided into 6 groups each consisting of 7 rats/group; Control, APAP (250 mg/kg, ip), Acute Exercise (AEx), Acute Exhaustive Exercise (AEEx), Acute Exercise and APAP (AEx+APAP) and Acute Exhaustive Exercise and APAP (AEEx+APAP) groups. Rats were exercised at moderate intensity or exhaustive on the treadmill and then received APAP. Tissue MDA levels were significantly increased in AEEx, AEx+APAP and AEEx+APAP groups compared with the control. There was no significant difference in GSH levels between groups. Tissue Sirtuin1 (Sirt1) levels of APAP, AEx and AEEx groups were significantly less than control. There was no significant difference between groups in VEGF levels. Liver damage score was significantly higher in all groups compared with control group. As a result, this study shows that subtoxic dose of APAP treatment alone or in combination with acute or exhaustive treadmill exercise can cause oxidative liver damage by affecting Sirt1 levels and without affecting VEGF levels.

L-Glutamine is better for treatment than prevention in exhaustive exercise.

Introduction: Glutamine is known as the richest nonessential amino acid in the human body. The intake of glutamine is not only beneficial to nutrition but also reported to enhance inflammation reducing bioactivity in exercise. Although studies have demonstrated that glutamine is beneficial for exercise, the optimal intake timing remains unclear. This study examined whether the effects of glutamine on tissue damage and physiology differ between intake timings. Methods: Rats were divided into without L-glutamine supplementation (vehicle), with L-glutamine before exhaustive exercise (prevention), and with L-glutamine after exhaustive exercise (treatment) groups. Exhaustive exercise was induced by treadmill running and L-glutamine was given by oral feeding. The exhaustive exercise began at a speed of 10miles/min and increased in increments of 1mile/min, to a maximum running speed of 15miles/min with no incline. The blood samples were collected before exhaustive exercise, 12h and 24h after exercise to compare the creatine kinase isozyme MM (CK-MM), red blood cell count and platelet count. The animals were euthanized on 24h after exercise, and tissue samples were collected for pathological examination and scored the severity of organ injury from 0 to 4. Results: The CK-MM was elevated gradually after exercise in the vehicle group; however, CK-MM was decreased after L-glutamine supplementation in the treatment group. The treatment group had higher red blood cell count and platelet count than the vehicle and prevention group after exercise. In addition, the treatment group had less tissue injury in the cardiac muscles, and kidneys than prevention group. Conclusion: The therapeutic effect of L-glutamine after exhaustive exercise was more effective than preventive before exercise.

Magnesium ions improve vasomotor function in exhausted rats.

To observe the effect of magnesium ion on vascular function in rats after long-term exhaustive exercise. Forty male SD rats were divided into two groups, the control group (CON group, n = 20) and the exhaustive exercise group (EEE group, n = 20). Exhausted rats performed 1W adaptive swimming exercise (6 times/W, 15min/time), and then followed by 3W formal exhaustive exercise intervention. Hematoxylin and eosin (HE) staining was used to detect the morphological changes of rat thoracic aorta. The contents of interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum of rats were determined by enzyme-linked immunosorbent assay (ELISA), and the contents of malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO) and endothelin 1 (ET-1) in serum of rats were determined by biochemical kit. Vascular ring test detects vascular function. Compared with the CON group, the smooth muscle layer of the EEE group became thicker, the cell arrangement was disordered, and the integrity of endothelial cells was destroyed; the serum Mg2+ in EEE group was decreased; the serum levels of IL-1β, TNF-α, MDA and ROS in EEE group were significantly higher than those in the CON group (P are all less than 0.05); the serum NO content in EEE group was significantly decreased, and the ratio of NO/ET-1 was significantly decreased. In the exhaustion group, the vasoconstriction response to KCl was increased, and the relaxation response to Ach was weakened, while 4.8mM Mg2+ could significantly improve this phenomenon (P are all less than 0.01). The damage of vascular morphology and function in rats after exhaustion exercise may be related to the significant increase of serum IL-1β, TNF-α, ROS, MDA and ET-1/NO ratio in rats after exhaustion exercise, while Mg2+ can significantly improve the vasomotor function of rats after exhaustion exercise.

Exercise preconditioning improves electrocardiographic signs of myocardial ischemic/hypoxic injury and malignant arrhythmias occurring after exhaustive exercise in rats

Exercise preconditioning (EP) has a good myocardial protective effect. This study explored whether EP improves electrocardiographic (ECG) signs of myocardial ischemic/hypoxic injury and the occurrence of malignant arrhythmia after exhaustive exercise. A total of 120 male SD rats were randomly divided into the control group (group C), early exercise preconditioning group (group EEP), late exercise preconditioning group (group LEP), exhaustive exercise group (group EE), early exercise preconditioning + exhaustive exercise group (group EEP + EE) and late exercise preconditioning + exhaustive exercise group (group LEP + EE). Changes in heart rate (HR), ST segment, T wave and QT corrected (QTc) intervals on ECG; hematoxylin-basic fuchsin-picric acid (HBFP) staining; and cTnI levels were used to study myocardial injury and the protective effect of EP. Compared with those in group C, the levels of plasma markers of myocardial injury, HBFP staining and ECG in group EE were significantly increased (P < 0.05). Compared with those in group EE, the levels of plasma markers of myocardial injury, HBFP staining and ECG in group EEP + EE and group LEP + EE were significantly decreased (P < 0.05). The results suggested that EP improved ECG signs of myocardial ischemic/hypoxic injury and malignant arrhythmias that occur after exhaustive exercise. The ST segment and T wave could also serve as indexes for evaluating exhaustive exercise-induced myocardial ischemia/hypoxia.

Effects of exhaustive exercise on coagulation state in rats

Objective: To investigate the effects of one-time exhaustive exercise on coagulation state in rats and its mechanism. Methods: Forty-eight SD rats were randomly divided into control group and exhaustive exercise group, 24 rats in each group. Rats in exhaustive exercise group were trained with treadmill training for 25～50 min at a time on non-slope treadmill and the initial speed of 5 m/min was uniformly accelerated to 25 m/min until the rats exhausted. Thrombelastography (TEG) was used to monitor the coagulation function of rats after training. The ligation model of inferior vena cava (IVC) was established to evaluate thrombosis. The phosphatidylserine (PS) exposure and Ca2+ concentration were detected by flow cytometry. The production of FXa and thrombin was detected by microplate reader. The clotting time was measured by using coagulometer. Results: Compared with the control group, the blood of rats in the exhaustive exercise group exhibited hypercoagulable state. The probability of thrombus formation, weight, length and ratio in the exhaustive exercise group were significantly higher than those in the control group (P＜0.01). The levels of PS exposure and intracellular Ca2+ concentration of red blood cells (RBCs) and platelets in the exhaustive exercise group were increased significantly (P＜0.01). The blood clotting time of RBCs and platelets was shortened (P＜0.01), and the production of FXa and thrombin was increased significantly (P＜0.01) in the exhausted exercise group, and both were inhibited by lactadherin (Lact, P＜0.01). Conclusion: The blood of exhaustive exercise rats is in a hypercoagulable state and the risk of thrombosis is increased. The increased PS exposure of RBCs and platelets caused by exhaustive exercise may be an important mechanism of thrombosis.

Experimental study of mitochondrion-targeted small molecule IR-61 ameliorated exhaustive exercise-induced cardiac injury in rats

To investigate the effects of mitochondrion-targeted cyanine fluorescent small molecule IR-61 on cardiac injury induced by exhaustive exercise in rats. Thirty-six adult male SD rats were randomly divided into 3 groups(n=12),control group (Ctrl), exhaustive exercise group (EE) and IR-61+ exhaustive exercise group (IR-61+EE). IR-61+EE group were intraperitoneally injected with 2 mg/kg IR-61 at the same time on day 1, 4 and 7. One hour after the end of the last drug administration, the two exhaustive exercise groups were subjected to exhaustive exercise modeling. The rats were placed on an animal treadmill with a slope of 0° at a speed of 10~15 m/min to coordinate their limbs running posture, and then ran at a speed of 25~30 m/min until exhaustion about 15 minutes later. After the animal models established, ECG was recorded by physiological recorder, myocardial injury was observed by light microscope, mitochondrial injury was observed by transmission electron microscope, myocardial cell apoptosis was detected by TUNEL method, markers of myocardial injury were detected by ELISA, and myocardial mitochondrial respiration rate was measured by high-resolution Oxygraph-2K mitochondrial instrument. ① Compared with Ctrl group, heart rate was increased, PR interval was shortened, QRS interval was prolonged, QTc was prolonged and ST segment was depressed significantly in EE group (P＜0.05). In EE group, myocardial fiber fracture and mitochondrial inner chamber swelling were obvious, mitochondrial crest was fuzzy, mitochondrial outer membrane was incomplete, and a large number of mitochondrial rupture and fusion were visible. In EE group, TUNEL staining cells were abundant, chromatin concentration and marginalization, nuclear membrane lysis, chromatin fragmentation into massive apoptotic bodies, apoptosis score increased (P＜0.05). The levels of creatine kinase isoenzyme-MB (CK-MB), cardiac troponin I(cTn-I) and N-terminal B-type natriuretic peptide (NT-proBNP) were increased in EE group (P＜0.05). Basal respiration rate, oxidative respiration rate of fatty acids and respiration rate of complex Ⅰ, Ⅱ and Ⅳ were all decreased (P＜ 0.05). ② Compared with EE group, the heart rate in IR-61+EE group was increased, PR interval was prolonged, QRS interval was shortened, QTc was shortened, ST segment was not significantly depressed (P＜0.05). In IR-61+EE group, myocardial fiber arrangement was loose, no obvious fracture was observed, mitochondrial inner ventricle was swelling, mitochondrial outer membrane was intact, TUNEL stained cells and unstained cells were observed, the overall morphology was more similar to Ctrl group. Apoptosis index was decreased (P＜0.05), the levels of CK-MB and cTn-I were decreased in IR-61+EE group (P＜0.05). The oxidative respiration rate of fatty acids and the respiration rate of complex Ⅱ and Ⅳ were increased (P＜0.05). Mitochondrion-targeted cyanine fluorescent small molecule IR-61 can improve cardiac electrical activity, reduce myocardial cell injury and mitochondrial injury, reduce myocardial cell apoptosis, and improve the myocardial mitochondrial energy metabolism condition in exhausted rats.

Assessment of Exhaustive Exercise under Internet of Things Exercise Monitoring System and Mechanism Analysis of Cardiovascular Endothelial Cell Apoptosis Induced by Oxidative Stress

To investigate the effect of high-intensity exhaustive exercise on body and the molecular mechanism of oxidative stress regulating apoptosis of cardiovascular endothelial cells (CVECs), 70 college students who took an aerobics course were recruited as the research subjects, all of which were divided into the high-intensity group (35 students) and the moderate-intensity group (35 students). The Internet of Things- (IoT-) based human exercise information monitoring system was employed to collect the electrocardiogram, serum indexes, and oxidative stress indexes of the two groups of subjects after exercise. Moreover, 30 clean male SD rats were divided into exhaustive exercise group ( n = 10 ), routine exercise group ( n = 10 ), and blank control group ( n = 10 ) using treadmill exercise as stress source, and various physiological indexes of the three groups were compared. In human experiments, the time-domain indexes of heart rate variability (HRV), 50 ms in the total number of sinus heartbeats (PNN50), the standard deviation of all NN intervals (SDNN), standard deviation of mean NN interval (SDANN), standard deviation of difference between adjacent NN intervals (SDSD), root mean square (RMSSD) in the high intensity group were lower than those in the moderate intensity group ( P &lt; 0.05 ). The levels of T-sensitive troponin I (Tnl-ultra), cortisol (COR), high-sensitive troponin T (TnT-hs), high-sensitive C-reactive protein (hs-CRP), and human heart-type fatty acid binding protein (HUMAN H-FABP) in high intensity group were higher than those in moderate intensity group ( P &lt; 0.05 ). Experiments on animals found that SOD content and mRNA expression of fork-head box 03A (FOX03A) and silencing-information regulator 1 (Sirtl) in serum of rats in exhaustion exercise group were lower than those in the routine exercise group and blank control group, while lactate dehydrogenase (LDH) and malondialdehyde (MDA) contents were opposite ( P &lt; 0.05 ). In short, strenuous exercise made the body in the state of acute stress, leading to the disturbance of cardiac autonomic nervous function and sympathetic nervous function, and increasing the risk of malignant arrhythmia. Oxidative stress induced by exhaustive exercise may promote the apoptosis of CVECs by reducing the expression of Sirtl and FOX03A and locating FOX03A to the nucleus.

Optimization of exercise preconditioning duration in protecting from exhausted exercise-induced cardiac injury in rats.

The effect of different duration of exercise preconditioning (EP) on protecting from exhaustive exercise-induced cardiac injury (EECI) has been optimized in rats. Male Sprague-Dawley rats were divided into six groups: the control group, exhaustive exercise (EE) group, EP 20-min + EE group, EP 40-min + EE group, EP 60-min + EE group and EP 80-min + EE group. The EP groups were subjected to treadmill running at the intensity of 74.0% V̇O2 max. Changes of exercise capacity, cardiac pathology, myocardial enzymology, electrocardiogram (ECG), cardiac function, and mitochondrial respiratory function were compared. Compared to the C group, the EE group has shown significant decrease of exercise capacity, elevation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTn-I) levels, cardiac morphology change, ECG disturbance, cardiac dysfunction and reduction of myocardial mitochondrial respiration function. Compared to the EE group, the EP groups have shown significant elevation of exercise capacity, decrease of serum NT-proBNP and cTn-I, improvement of cardiac function and myocardial mitochondrial electron transfer pathway complex I, II and IV activity. The correlation analyses showed protection of EP was proportional to EP duration from 20-min to 60-min. EE caused cardiac injury. EP could protect from EECI by alleviating myocardial damage, improving cardiac function and mitochondrial ETP complex I, II and IV activity. EP protection was positively correlated to EP duration from 20-min to 60-min with EP intensity fixed at 74.0% V̇O2 max.

Effects of acute endurance exercise and exhaustive exercise on innate immune signals induced by mtDNA

Objective: Numerous studies have shown that mitochondrial DNA (mtDNA) can trigger innate immune signaling, and exercise can induce mitochondrial stress. Therefore, this study is aimed at investigating the influence of different types of acute exercise on the innate immune signaling triggered by mtDNA. Methods: Male C57BL/6 mice ( n = 18) were randomly and equally divided into three groups. They were control group, acute moderate-intensity endurance exercise group (AMIE), and 3-day exhaustive exercise group (EE) respectively. Mice were sacrificed immediately after exercise. The spleen, liver, and blood were taken for analysis. Results: The amount of mtDNA in the liver cytoplasm and plasma was significantly decreased after AMIE ( p &lt; .05). However, the amount of mtDNA in plasma was increased after EE (p &lt; .05). The mRNA expression of TFAM, and most TLR9 and cGAS/STING signaling pathway-related genes in the liver and spleen was markedly elevated, whereas the expression of those genes in leukocytes was reduced after AMIE. Furthermore, AMIE significantly decreased the protein expression of NLRP3 inflammasome in the liver ( p &lt; .05) and STING in spleen ( p &lt; .01). Also, AMIE and EE caused a drop in circulating IFN-β levels ( p &lt; .05). Conclusion: A single bout of moderate-intensity exercise reduces mtDNA-induced innate immune signaling and suppresses inflammatory responses by decreasing hepatic cytoplasmic and circulating mtDNA. However, repeated bouts of exhaustive exercise stimulate innate immune signaling by increasing levels of circulating mtDNA.

EFFECTS OF EXHAUSTIVE EXERCISE AND CONTUSION ON AUTOPHAGY-RELATED FACTORS IN SKELETAL MUSCLE OF RATS

ABSTRACT Objective: To study the effects of exhaustive exercise and contusion on autophagy-related factors Beclin1, LC3 and PINK1 expression in the skeletal muscle of rats. Methods: Forty-two male SD rats were randomly divided into 7 groups, 6 rats in each group: C, D0, D24, D48, E0, E24, and E48. Each group of rats was killed and dissected at the different respective time points specified above. The whole quadriceps femoris of the left hind limbs were removed and divided into two parts, one for mRNAs of Beclin1, LC3 and PINK1 by real-time fluorescent quantitative PCR, and the other for LC3 protein by Western blotting. Results: Compared with group C, the contents of Beclin1 mRNA, PINK1 mRNA, and LC3 mRNA in the immediate exhaustive exercise group (E0) were significantly reduced p&lt;0.01. However, the levels of PINK1 mRNA, LC3 mRNA, and LC3 protein in skeletal muscle cells increased significantly in the 48 hours after exhaustion (E48) p&lt;0.05, suggesting that cell autophagy had an increasing trend during the recovery period. Meanwhile, compared with the C group, the contents of Beclin1 mRNA, PINK1 mRNA, and LC3 mRNA in the immediate blunt contusion group (D0) increased significantly p&lt;0.01 and were followed by a downward trend. Conclusion: Generally, there were differences between the blunt contusion and exhausted exercise models at each recovery phase. The gene expression of the autophagy-related factors was not high in the early exhaustive exercise recovery phase and subsequently followed an upward trend. But the above factors increased significantly in the immediate and early recovery phases after blunt contusion. Injury from blunt contusion may be more severe than exhaustive exercise-induced-injury, so the autophagy starts earlier according to the changes in autophagy-related factors. Level of evidence III; Therapeutic studies investigating the results of treatment.

Optimization of different intensities of exercise preconditioning in protecting exhausted exercise induced heart injury in rats

This study was to optimize the exercise preconditioning (EP) intensity in protecting from exhaustive exercise-induced cardiac injury (EECI). A total of 98 male Sprague-Dawley rats were divided into 7 groups (n ​= ​14): the control group (C), the exhaustive exercise group (EE) and the EP ​+ ​EE groups, which include the V10 (53.0%̇O2max), V15 (58.4%̇O2max), V20 (67.0%̇O2max), V26 (74.0%̇O2max) and V30 (80.0%̇O2max) groups. Except the C group, the other groups were subjected to treadmill running. The serum contents of N terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTn-I) were detected by the enzyme-linked immunosorbent assay method, ECG was recorded, heart function was detected by pressure volume catheter and the activities of mitochondrial electron transfer pathway (ET pathway) complexes I, Ⅱ and IV were measured by high-resolution respiration instrument. Compared to the EE group, the EP groups have shown decrease of NT-proBNP and cTn-I, improvement of mitochondrial respiratory function and cardiac function. Compared to other EP groups, the V26 group has shown significant decrease of myocardial enzymes and improvement of mitochondrial function. The correlation analysis showed the EP effect was proportional to EP intensity in the range of 53.0%̇O2max-74.0%̇O2max. High intensity and long duration of exhaustive exercise caused cardiac injury and EP could decrease serum level of NT-proBNP and cTn-I, improve electrical derangement and the left ventricular function, and raise the activities of ET pathway complexes I, Ⅱ and IV. The protection of EP on EECI was improved as the EP intensity was increased from 53.0%̇O2max to 74.0%̇O2max and when EP intensity was 74.0%̇O2max, the effect was the most obvious among all the setting EP groups.

Physiological and Psychological Effects of Treadmill Overtraining Implementation.

Simple SummaryOvertraining occurs when an imbalance between training stress and recovery exists, and it is prevalent in athletes, soldiers, physical education, and health education undergraduates as well as a number of female and male adolescents. Despite a broad body of evidence concerning physiological and psychological correlates of this syndrome, the pathomechanisms of overtraining are still poorly understood. This illustrates the need to establish animal models of this disorder. This article outlines and discusses physiological and psychological effects of the current established overtraining model, based on an eight-week exhaustive treadmill exercise that reveals the involvement of imbalanced energy expenditure, exacerbated inflammatory response, increased intestinal permeability, and anxiety status in the development and onset of overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies.Overtraining in athletes usually causes profound and lasting deleterious effects on the maintenance of health and exercise capacity. Here, we established an overtraining animal model to investigate the physiological modulation for future strategic applications in vivo. We subjected C57BL/6 mice to exhaustive treadmill exercises daily for 8 weeks (the exhaustive exercise group). Next, the physiological and psychological outcomes were compared with the regular exercise and sedentary groups. Outcome measures included growth, glucose tolerance, exercise metabolism profiles, cytokine levels, intestinal tight junction gene expression, and psychological behavioral changes. Our results revealed that overtraining negatively affected the physiological and psychological changes in the current model. The exhaustive exercise group exhibited significantly lower endurance performance and imbalanced energy expenditure, causing a decrease in body fat mass and slowing down the growth curve. In addition, the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) and immune cells (neutrophils and monocytes) were significantly elevated after successive exhaustive exercise interventions. Furthermore, overtraining-induced stress resulted in increased anxiety status and decreased food intake. Our findings reinforce the idea that an imbalance between exercise and recovery can impair health and performance maintenance after overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies.

Metabolomics study on the intervention effect of Radix Salviae Miltiorrhizae extract in exercise-induced exhaustion rat using gas chromatography coupled to mass spectrometry

The metabolomics approach based on the gas chromatography coupled to mass spectrometry (GC-MS) was adopted to explore the underlying mechanism of the anti-fatigue effect of Radix Salviae Miltiorrhizae (RSM), a famous herbal medicine in China used for multiple biological functions, in load-weighted swimming test in rat, combined with biochemical parameters evaluations. As a result, the metabolomics study followed by orthogonal partial least-square (OPLS) analysis could differentiate metabolic profiling between the control and exhaustive exercise group, showing the rats underwent an obvious metabolic perturbation, whereas RSM treatment restored scores plot close to normal and showed regulatory effects on the muscle metabolic profiles. The changed metabolic pathways of the potential biomarkers in response to the effect of RSM treatment for exhaustive exercise rats included in glucose metabolism (glucose, lactic acid, alanine), glutathione metabolism (glycine, glutamate, 5-oxo-proline), TCA cycle (succinic acid), arginine biosynthesis (glutamine, ornithine, urea), glyoxylate and dicarboxylate metabolism (serine, glycine), oxidative stress (taurine) and purine metabolism (inosine). In addition, intervention of RSM increased hepatic glycogen, muscle glycogen and serum glucose, and decreased triglyceride and blood urea nitrogen levels, indicating RSM treatment may regulate energy metabolism by increasing the rate of fat utilization, decrease the protein and carbohydrate utilization. Furthermore, RSM reduced exhaustive exercise-induced accumulation of the lipid peroxidation byproduct malonaldehyde and elevated antioxidants' levels, including reduced glutathione and superoxide dismutase, which might be a positive reflection of improved oxidant-antioxidant balance. Moreover, RSM could protect against exercise-induced muscle damage by attenuating creatine kinase release. In summary, RSM provided a good anti-fatigue effect by regulating energy metabolism, oxidant-antioxidant balance, and the endogenous metabolites in the exercising muscle. This study demonstrates that metabolomics is an effective tool for the estimation of the potential anti-fatigue effect of RSM and for the illustration of its pharmacological mechanism.

Exercise Preconditioning Increases Beclin1 and Induces Autophagy to Promote Early Myocardial Protection via Intermittent Myocardial Ischemia-Hypoxia.

Exercise preconditioning (EP) provides protective effects for acute cardiovascular stress; however, its mechanisms need to be further investigated. Autophagy is a degradation pathway essential for myocardium health. Therefore, we investigated whether intermittent myocardial ischemia-hypoxia affected Beclin1 and whether the changes in autophagy levels contribute to EP-induced early myocardial protective effects. Rats were trained on a treadmill using an EP model (four cycles of 10 minutes of running/10 minutes of rest). Exhaustive exercise (EE) was performed to induce myocardial injury. Cardiac troponin I (cTnI) and ischemia-hypoxia staining were used to evaluate myocardial injury and protection. Double-labeled immunofluorescence staining and western blot analysis were employed to examine related markers. EP attenuated the myocardial ischemic-hypoxic injury induced by EE. Compared with the control (C) group, the dissociations of Beclin1/Bcl-2 ratio and Beclin1 expression were both higher in all other groups. Compared with the C group, PI3KC3 and the LC3-II/LC3-I ratio were higher in all other groups, whereas LC3-II was higher in the EE and EEP + EE groups. p62 was higher in the EE group than in the C group but lower in the EEP + EE group than in the EE group. We concluded that EP increases Beclin1 via intermittent myocardial ischemia-hypoxia and induces autophagy, which exerts early myocardial protective effects and reduces the myocardial ischemic-hypoxic injury induced by exhaustive exercise.

Study on the time-effectiveness of exercise preconditioning on heart protection in exhausted rats.

To investigate the persistence time and the effectiveness of exercise preconditioning (EP) on myocardial protection in exhausted rats from myocardial enzymes, electrocardiogram (ECG), cardiac function, and mitochondrial respiratory function after cessation of exercise training. One hundred and twelve healthy male Sprague-Dawley rats were randomly divided into seven groups (n = 16): control group (CON), exhaustive exercise (EE) group, EP group, and EE after EP (EP + EE); furthermore, EP + EE group was randomly divided into 1D, 3D, 9D, and 18D groups (1D, 3D, 9D, and 18D) and performed exhaustive treadmill exercise at a speed of 30 m/min on the 1st, 3rd, 9th, and 18th days separately after EP exercise stopped. We detected the serum contents of N-terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) by the enzyme-linked immunosorbent assays method, recorded ECG, detected heart function by pressure volume catheter, measured the respiratory rates of rat myocardial mitochondria state 3 and 4 of complex I, complex II, and IV by high-resolution breathing apparatus. EP could decrease the serum content of NT-proBNP and cTnI, improved the electrical derangement and the left ventricular function in exhausted rats. Moreover, the protective effect was more obvious in the 9th day after EP stopped, whereas it would disappear when EP stopped for more than 18 days. Compared with EE group, the respiratory rate value of myocardial mitochondrial complex increased in 1D, 3D, and 9D groups. Therefore, the protective effect of EP on the heart of exhausted rats decreased with the prolongation of stopping training time, and the effect was significant within 3 days of discontinuing training, then decreased gradually, and completely disappeared in the 18th day. EP enhanced the cardiac function in exhausted rats through raising the nicotinamide adenine diphosphate hydride (NADH) electron transport chain and increased the respiration rates of mitochondrial respiratory complex I and IV state 3, thereby improved myocardial mitochondrial respiratory function and energy metabolism.

Rhodiola Crenulata ameliorates exhaustive exercise‑induced fatigue in mice by suppressing mitophagy in skeletal muscle

The aim of present study was to evaluate the potential effects of Rhodiola crenulata oral liquid (RCOL) on exhaustive exercise (EE)-induced fatigue in mice. Male Institute of Cancer Research mice from five treatment groups (n=10 per group) were orally administered with sterilized water for the Control and EE groups and/or RCOL at doses of 1.02, 3.03 and 6.06 ml/kg/day, once daily for 2 weeks. Anti-fatigue activity was subsequently evaluated by measuring the levels of creatine kinase (CK), lactic acid (LA), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and total anti-oxidative capability (T-AOC). Histopathology was assessed using hematoxylin and eosin staining. Ultrastructures of mitochondria were observed by transmission electron microscopy. Energy supply capacity was assessed using citrate synthase (CS), succinate dehydrogenase (SDH), Na+-K+-ATPase, and liver and quadriceps glycogen content assays. Expression levels of mRNA and protein associated with mitophagy in the skeletal muscle were measured by reverse transcription-quantitative PCR and western blotting, respectively. RCOL was observed to markedly inhibit fatigue-induced oxidative stress by increasing the activities of SOD, CAT and T-AOC, whilst reducing the accumulation of LA, CK, LDH and MDA. Histological analysis of the quadriceps femoris tissue suggested increased numbers of muscle fibers in the RCOL groups compared with those in the EE group. RCOL administration was found to reverse EE-induced mitochondrial structural damage and alleviated defects inflicted onto the energy supply mechanism by increasing CS, SDH, Na+-K+-ATPase and glycogen levels. Additionally, RCOL reduced the protein expression of PTEN-induced kinase 1 (PINK1), Parkin, microtubule-associated proteins 1A/1B light chain 3, sequestosome 1 and ubiquitin, whilst lowering the gene expression of PINK1 and Parkin. Taken together, results from the present study clarified the anti-fatigue effect of RCOL, where the underlying mechanism may be associated with increased antioxidant activity, enhanced energy production and the inhibition of mitophagy by suppressing the PINK1/Parkin signaling pathway.

Different Intensity Exercise Preconditions Affect Cardiac Function of Exhausted Rats through Regulating TXNIP/TRX/NF-ĸBp65/NLRP3 Inflammatory Pathways.

Objective To investigate whether exercise preconditioning (EP) improves the rat cardiac dysfunction induced by exhaustive exercise (EE) through regulating NOD-like receptor protein 3 (NLRP3) inflammatory pathways and to confirm which intensity of EP is better. Method Ninety healthy male Sprague Dawley rats were randomly divided into five groups: a control group (CON), exhaustive exercise group (EE), low-, middle-, and high-intensity exercise precondition and exhaustive exercise group (LEP + EE, MEP + EE, HEP + EE group). We established the experimental model by referring to Bedford's motion load standard to complete the experiment. Then, the pathological changes of the myocardium were observed under a light microscope. Biomarker of myocardial injury in serum and oxidative stress factor in myocardial tissue were evaluated by ELISAs. The cardiac function parameters were detected using a Millar pressure and volume catheter. The levels of thioredoxin-interacting protein (TXNIP), thioredoxin protein (TRX), nuclear transcription factor kappa Bp65 (NF-ĸBp65), NLRP3, and cysteinaspartate specific proteinase 1 (Caspase-1) protein in rats' myocardium were detected by western blotting. Results 1. The myocardial structures of three EP + EE groups were all improved compared with EE groups. 2. The levels of the creatine phosphating-enzyme MB (CK-MB), reactive oxygen species (ROS), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α) in three EP + EE groups were all increased compared with CON but decreased compared with the EE group (P < 0.05). 3. Compared with the CON group, slope of end-systolic pressure volume relationship (ESPVR), ejection fraction (EF), and peak rate of the increase in pressure (dP/dtmax) all dropped to the lowest level in the EE group (P < 0.05), while the values of cardiac output (CO), stroke volume (SV), end-systolic volume (Ves), end-diastolic volume (Ved), and relaxation time constant (Tau) increased in the EE group (P < 0.05). 4. Compared with the CON group, the expression levels of TXNIP, NF-ĸBp65, NLRP3, and Caspase-1 all increased obviously in the other groups (P < 0.05); meanwhile, they were all decreased in three EP + EE groups compared with the EE group (P < 0.05). 5. NLRP3 was positively correlated with heart rate, IL-6, and ROS, but negatively correlated with EF (P < 0.01). Conclusion EP protects the heart from EE-induced injury through downregulating TXNIP/TRX/NF-ĸBp65/NLRP3 inflammatory signaling pathways. Moderate intensity EP has the best protective effect.

Exercise Preconditioning Plays a Protective Role in Exhaustive Rats by Activating the PI3K-Akt Signaling Pathway.

Objective To investigate whether exercise preconditioning (EP) protects the rat heart from exhaustive exercise- (EE-) induced injury by inducing the PI3K-Akt signaling pathway. Methods 84 male Sprague-Dawley rats were randomly divided into 6 groups (n = 14 rats per group): control group (Con), exhaustive exercise group (EE), exercise preconditioning group (EP), exercise preconditioning + exhaustive exercise group (EP + EE), LY294002 (PI3K inhibitor) + exercise preconditioning + exhaustive exercise group (LY + EP + EE), and LY294002 group (LY). The Con and LY did not exercise. The remaining groups were subjected to treadmill running. The structure of myocardial tissue and serum biomarkers of myocardial injury were observed. Hemodynamic parameters were recorded with a pressure-volume catheter. TUNEL assay was used to detect the apoptosis of cardiac myocytes, and the level of mitochondrial membrane permeability transforming pore (mPTP) in myocardium was evaluated using ELISA. Pathway and apoptosis-related proteins in myocardium were assessed using western blotting. Results Compared to the Con group, the EE group showed remarkable myocardial injury, such as cardiac dysfunction and myocardial apoptosis. Compared to the EE group, the injuries in the EP + EE group were improved. EP increased the PI3K-Akt signaling pathway and regulated Bcl-2 family to decrease the mPTP openness level. However, the cardioprotective effects of EP were attenuated when pretreated with the LY294002. Conclusions EP protected the heart from EE-induced injury, and it may improve the cardiac function and reduce the cardiomyocyte apoptosis by activating the PI3K-Akt signaling pathway.