Caffeine effects on systemic metabolism, oxidative-inflammatory pathways, and exercise performance.

Caffeine, a xanthine alkaloid compound, is consumed widely and daily by humans, as it is present in several regular beverages such as tea, coffee, soda beverages, and some drugs. Its consumption triggers arousal and alertness, improves mood, and causes the release of catecholamines, which induce beneficial effects on human behavior. Nonetheless, caffeine has been related to other beneficial effects such as antioxidant and anti-inflammatory actions that are extremely important to human health, altering the cellular redox and inflammatory status in a dose-dependent manner. Caffeine intake has also shown ergogenic effects, which are attributed to different factors, such as enhanced substrate utilization, fatigue delay, and alertness. As such, caffeine has been consumed by athletes from different sports modalities, with positive and negative effects declared. Although peripheral tissues such as the heart, skeletal muscle, and adipocytes are also impacted, there is a deficit of recognized mechanisms in systemic metabolism when compared to caffeine action in the central nervous system. This review summarizes the most relevant classical and current literature available regarding the use of caffeine in different metabolic situations, such as oxidative and inflammatory status, as well as anaerobic and aerobic physical exercises. Here, we identified the non-central nervous system caffeine mechanisms modulation, as most are still unknown or controversial, highlighting its influence in the peripheral system and its essential and crucial impacts on the human's organism adaptation.

Diclofenac attenuates inflammation through TLR4 pathway and improves exercise performance after exhaustive swimming.

BACKGROUND: The use of NSAIDs has become a common practice to counteract the pro-inflammatory acute effects of exercise, in order to improve sports performance. The liver, due to its central role in energy metabolism, may be involved primarily in the process of ROS generation and consequently inflammation after exhaustive exercise. OBJECTIVE: To analyze the influence of diclofenac on the liver TLR4 pathway and time to exhaustion in rats submitted to repeated exhaustive swimming. METHODS: An exhaustive test was performed in order to mimic athletes' routine, and inflammatory status and oxidative stress markers were evaluated in the liver. Animals were divided into sedentary and exhaustion groups, with this last performing three exhaustive swimming bouts. At the same time, diclofenac or saline was pre-administered once a day for nine days. RESULTS: Data showed significantly increased COX-2, TLR4, and MyD88 protein content in the liver after exhaustive swimming bouts. The levels of pro-inflammatory cytokines also increased after exhaustive exercise, while these effects were attenuated in the group treated with diclofenac plus exhaustive swimming bouts. The anti-inflammatory modulation provoked by diclofenac treatment was associated with an increased time to exhaustion in the exercise bouts. The exhaustive exercise increased TBARS formation, but diclofenac treatment blunted this elevation, while GSH/GSSG ratios in both exhaustion-saline and exhaustion-diclofenac-treated groups were lower than in the sedentary-saline group. CONCLUSIONS: Our findings suggest that diclofenac may improve exercise performance and represent an effective tool to ameliorate the pro-inflammatory status in liver when associated with exhaustive exercise, and the liver may be a possible therapeutic target.

Increased xanthine oxidase-related ROS production and TRPV1 synthesis preceding DOMS post-eccentric exercise in rats.

AIMS: It is well-known that unaccustomed exercise, especially eccentric exercise, is associated to delayed onset muscle soreness (DOMS). Whether DOMS is associated with reactive oxygen species (ROS) and the transient receptor potential vanilloid 1 (TRPV1) is still an open question. Thus, the aim of this study was to investigate the association between TRPV1 and xanthine oxidase-related ROS production in muscle and DOMS after a bout of eccentric exercise. MAIN METHODS: Male Wistar rats performed a downhill running exercise on a treadmill at a -16° tilt and a constant speed for 90min (5min/bout separated by 2min of rest). Mechanical allodynia and grip force tests were performed before and 1, 3, 6, 9, 12, 24, 48 and 72h after the downhill running. Biochemical assays probing oxidative stress, purine degradation, xanthine oxidase activity, Ca(2+) ATPase activity and TRPV1 protein content were performed in gastrocnemius muscle at 12, 24, and 48h after the downhill running. KEY FINDINGS: Our statistical analysis showed an increase in mechanical allodynia and a loss of strength after the downhill running. Similarly, an increase in carbonyl, xanthine oxidase activity, uric acid levels and TRPV1 immunoreactivity were found 12h post-exercise. On the other hand, Ca(2+) ATPase activity decreased in all analyzed times. SIGNIFICANCE: Our results suggest that a possible relationship between xanthine oxidase-related ROS and TRPV1 may exist during the events preceding eccentric exercise-related DOMS.

Swimming training induces liver mitochondrial adaptations to oxidative stress in rats submitted to repeated exhaustive swimming bouts.

BACKGROUND AND AIMS: Although acute exhaustive exercise is known to increase liver reactive oxygen species (ROS) production and aerobic training has shown to improve the antioxidant status in the liver, little is known about mitochondria adaptations to aerobic training. The main objective of this study was to investigate the effects of the aerobic training on oxidative stress markers and antioxidant defense in liver mitochondria both after training and in response to three repeated exhaustive swimming bouts. METHODS: Wistar rats were divided into training (n = 14) and control (n = 14) groups. Training group performed a 6-week swimming training protocol. Subsets of training (n = 7) and control (n = 7) rats performed 3 repeated exhaustive swimming bouts with 72 h rest in between. Oxidative stress biomarkers, antioxidant activity, and mitochondria functionality were assessed. RESULTS: Trained group showed increased reduced glutathione (GSH) content and reduced/oxidized (GSH/GSSG) ratio, higher superoxide dismutase (MnSOD) activity, and decreased lipid peroxidation in liver mitochondria. Aerobic training protected against exhaustive swimming ROS production herein characterized by decreased oxidative stress markers, higher antioxidant defenses, and increases in methyl-tetrazolium reduction and membrane potential. Trained group also presented higher time to exhaustion compared to control group. CONCLUSIONS: Swimming training induced positive adaptations in liver mitochondria of rats. Increased antioxidant defense after training coped well with exercise-produced ROS and liver mitochondria were less affected by exhaustive exercise. Therefore, liver mitochondria also adapt to exercise-induced ROS and may play an important role in exercise performance.