Physical exercise-induced oxidative stress and inflammation may be beneficial when exercise is a regular activity, but it is rather harmful when exercise is exhaustive and performed by unaccustomed ...organisms. Molecular hydrogen (H
) has recently appeared as a potent antioxidant and anti-inflammatory molecule in numerous pathological conditions. However, its role is relatively unknown under physiological conditions such as physical exercise. Therefore, this review summarizes the current knowledge of the H
, reducing oxidative stress and inflammation in physical exercise, reporting data from both animal and human studies.
Physical exercise induces inflammatory and oxidative markers production in the skeletal muscle and this process is under the control of both endogenous and exogenous modulators. Recently, molecular ...hydrogen (H2) has been described as a therapeutic gas able to reduced oxidative stress in a number of conditions. However, nothing is known about its putative role in the inflammatory and oxidative status during a session of acute physical exercise in sedentary rats. Therefore, we tested the hypothesis that H2 attenuates both inflammation and oxidative stress induced by acute physical exercise. Rats ran at 80% of their maximum running velocity on a closed treadmill inhaling either the H2 gas (2% H2, 21% O2, balanced with N2) or the control gas (0% H2, 21% O2, balanced with N2) and were euthanized immediately or 3 h after exercise. We assessed plasma levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)−1β and IL-6 and oxidative markers superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx). In addition, we evaluated the phosphorylation status of intracellular signaling proteins glycogen synthase kinase type 3 (GSK3α/β) and the cAMP responsive element binding protein (CREB) that modulate several processes in the skeletal muscle during exercise, including changes in exercise-induced reactive oxygen species (ROS) production. As expected, physical exercise increased virtually all the analyzed parameters. In the running rats, H2 blunted exercise-induced plasma inflammatory cytokines (TNF-α and IL-6) surges. Regarding the oxidative stress markers, H2 caused further increases in exercise-induced SOD activity and attenuated the exercise-induced increases in TBARS 3 h after exercise. Moreover, GSK3α/β phosphorylation was not affected by exercise or H2 inhalation. Otherwise, exercise caused an increased CREB phosphorylation which was attenuated by H2. These data are consistent with the notion that H2 plays a key role in decreasing exercise-induced inflammation, oxidative stress, and cellular stress.
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•Exercise increased plasma cytokines and changed oxidative markers production.•H2 blunted exercise-induced inflammatory cytokines (TNF-α and IL-6) production.•H2 potentiated exercise-induced increases in SOD and blunted increases in TBARS.•H2 prevented exercise-induced increases in muscle CREB phosphorylation.•H2 effectively reduces acute exercise-induced inflammatory and oxidative status.
•H2 prevented LPS-induced hypotension by inhibiting NO production.•H2 reduced LPS-induced proinflammatory mediators production.•H2 increased anti-inflammatory responses during systemic ...inflammation.•H2 exerts a potent anti-inflammatory effect during systemic inflammation.
Molecular hydrogen (H2) exerts anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Here we tested the hypothesis that H2 modulates cardiovascular, inflammatory, and thermoregulatory changes in systemic inflammation (SI) induced by lipopolysaccharide (LPS) at different doses (0.1 or 1.5 mg/kg, intravenously, to induce mild or severe SI) in male Wistar rats (250–300 g). LPS or saline was injected immediately before the beginning of 360-minute inhalation of H2 (2% H2, 21% O2, balanced with nitrogen) or room air (21% O2, balanced with nitrogen). Deep body temperature (Tb) was measured by dataloggers pre-implanted in the peritoneal cavity. H2 caused no change in cardiovascular, inflammatory parameters, and Tb of control rats (treated with saline). During mild SI, H2 reduced plasma surges of proinflammatory cytokines (TNF-α and IL-6) while caused an increase in plasma IL-10 (anti-inflammatory cytokine) and prevented fever. During severe SI, H2 potentiated hypothermia, and prevented fever and hypotension, which coincided with reduced plasma nitric oxide (NO) production. Moreover, H2 caused a reduction in surges of proinflammatory cytokines (plasma TNF-α and IL-1β) and prostaglandin E2 (PGE2), in plasma and hypothalamus, and an increase in plasma IL-10. These data are consistent with the notion that H2 blunts fever in mild SI, and during severe SI potentiates hypothermia, prevents hypotension reducing plasma NO production, and exerts anti-inflammatory effects strong enough to prevent fever by altering febrigenic signaling and ultimately down-modulating hypothalamic PGE2 production.
Key points
The mechanisms involved in hypothermia and fever during systemic inflammation (SI) remain largely unknown.
Our data support the contention that brain‐mediated mechanisms are different in ...hypertension during SI.
Considering that, clinically, it is not easy to assess all mechanisms involved in cardiovascular and thermoregulatory control during SI, the present study sheds light on these integrated mechanisms that may be triggered simultaneously in septic hypertensive patients.
The result obtained demonstrate that, in lipopolysaccharide‐induced SI, an increased hypothermia is observed in neurogenic hypertension, which is caused by reduced hypothalamic prostaglandin E2 production and increased heat loss in conscious rats.
Therefore, the results of the present study provide useful insight for clinical trials evaluating the thermoregulatory outcomes of septic patients with hypertension.
Hypertension is a prevalent disease characterized by autonomic‐induced elevated and sustained blood pressure levels and abnormal body core temperature (Tb) regulation. The present study aimed to determine the brain‐mediated mechanisms involved in the thermoregulatory changes observed during lipopolysaccharide (LPS)‐induced systemic inflammation (SI; at a septic‐like model) in spontaneously hypertensive rats (SHR). We combined Tb and skin temperature (Tsk) analysis, assessment of prostaglandin (PG) E2 levels (the proximal mediator of fever) in the anteroventral region of the hypothalamus (AVPO; an important site for Tb control), oxygen consumption analysis, cardiovascular recordings, assays of inflammatory markers, and evaluation of oxidative stress in the plasma and brain of male Wistar rats and SHR that had received LPS (1.5 mg kg−1) or saline. LPS induced hypothermia followed by fever in Wistar rats, whereas, in SHR, a maintained hypothermia without fever were observed. These thermoregulatory responses were associated with an increased heat loss in SHR compared to Wistar rats. We measured LPS‐induced increased PGE2 levels in the AVPO in Wistar rats, but not in SHR. The LPS‐induced drop in blood pressure was higher in SHR than in Wistar rats. Furthermore, LPS‐induced plasma and brain regions involved in autonomic control: nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) cytokine surges were blunted, whereas oxidative stress was higher in SHR. LPS‐induced SI leads to blunted cytokine surges both systemically (plasma) and centrally (NTS and RVLM) and reduced hypothalamic PGE2 production, which are all associated with increased hypothermia mediated by increased heat loss, but not by heat production, in SHR.
Key points
The mechanisms involved in hypothermia and fever during systemic inflammation (SI) remain largely unknown.
Our data support the contention that brain‐mediated mechanisms are different in hypertension during SI.
Considering that, clinically, it is not easy to assess all mechanisms involved in cardiovascular and thermoregulatory control during SI, the present study sheds light on these integrated mechanisms that may be triggered simultaneously in septic hypertensive patients.
The result obtained demonstrate that, in lipopolysaccharide‐induced SI, an increased hypothermia is observed in neurogenic hypertension, which is caused by reduced hypothalamic prostaglandin E2 production and increased heat loss in conscious rats.
Therefore, the results of the present study provide useful insight for clinical trials evaluating the thermoregulatory outcomes of septic patients with hypertension.
We tested the hypothesis that the neuromodulator hydrogen sulfide (H2S) in the preoptic area (POA) of the hypothalamus modulates the febrigenic signaling differently in sedentary and trained rats. ...Besides H2S production rate and protein expressions of H2S-related synthases cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MPST) and cystathionine γ-lyase (CSE) in the POA, we also measured deep body temperature (Tb), circulating plasma levels of cytokines and corticosterone in an animal model of systemic inflammation. Rats run on a treadmill before receiving an intraperitoneal injection of lipopolysaccharide (LPS, 100 μg/kg) or saline. The magnitude of changes of Tb during the LPS-induced fever was found to be similar between sedentary and trained rats. In sedentary rats, H2S production was not affected by LPS. Conversely, in trained rats LPS caused a sharp increase in H2S production rate that was accompanied by an increased CBS expression profile, whereas 3-MPST and CSE expressions were kept relatively constant. Sedentary rats showed a significant LPS-induced release of cytokines (IL-1β, IL-6, and TNF-α) which was virtually abolished in the trained animals. Correlation between POA H2S and IL-6 as well as TNF-α was observed. Corticosterone levels were augmented after LPS injection in both groups. We found correlations between H2S and corticosterone, and corticosterone and IL-1β. These data are consistent with the notion that the responses to systemic inflammation are tightly regulated through adjustments in POA H2S production which may play an anti-inflammatory role downmodulating plasma cytokines levels and upregulating corticosterone release.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Exercise increased hippocampal cytokines levels without affecting oxidative stress•H2 blunted exercise-induced hippocampal TNF-α and IL-6 and increased the IL-10 surges•H2 caused no change in ...hippocampal oxidative markers•Inhaled H2 effectively reduces acute exercise-induced hippocampal inflammatory status
Physical exercise-induced inflammation may be beneficial when exercise is regular but it may be harmful when exercise is intense and performed by unaccustomed individuals/rats. Molecular hydrogen (H2) has recently emerged as a powerful anti-inflammatory, antioxidant and anti-apoptotic molecule in a number of pathological conditions, but little is known about its putative role under physiological conditions such as physical exercise. Therefore, we tested the hypothesis that H2 decreases intense acute exercise-induced inflammation in the hippocampus, since it is a brain region particularly susceptible to inflammation. Moreover, we also assessed hippocampus oxidative status. Rats ran on a sealed treadmill inhaling either the H2 (2% H2, 21% O2, balanced with N2) or the control gas (0% H2, 21% O2, balanced with N2) and hippocampal samples were collected immediately or 3 h after exercise. We measured hippocampal levels of cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 and oxidative markers superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx). Exercise increased TNF-α, IL-6 and IL-10 immediately after the session, whereas no change in IL-1β levels was observed. Conversely, exercise did not cause any change in SOD activity, TBARS and NOx levels. H2 inhibited the exercise-induced surges in TNF-α and IL-6, and potentiated the IL-10 surge, immediately after the exercise. Moreover, no change in IL1-β levels of rats inhaling H2 was observed. Regarding the oxidative stress markers, H2 failed to cause any change in SOD activity, TBARS and NOx levels. No significant change was observed in any of the assessed parameters 3 h after the exercise bout. These data are consistent with the notion that H2 acts as a powerful anti-inflammatory agent not only down-modulating pro-inflammatory cytokines (TNF-α and IL-6) but also upregulating an anti-inflammatory cytokine (IL-10) production without affecting the local oxidative stress status. These data indicate that H2 effectively decreases exercise-induced inflammation in the hippocampus, despite the fact that this region is particularly prone to inflammatory insults.
Physical exercise-induced skeletal muscle damage may be characterized by increased oxidative stress, inflammation, and apoptosis which may be beneficial when exercise is regular, but it is rather ...harmful when exercise is exhaustive and performed acutely by unaccustomed individuals. Molecular hydrogen (H
2
) has emerged as a potent antioxidant, anti-inflammatory, and anti-apoptotic agent, but its action on the deleterious effects of acute exhaustive exercise in muscle damage remain unknown. Therefore, we tested the hypothesis that H
2
decreases acute exhaustive exercise-induced skeletal muscle damage of sedentary rats. Rats ran to exhaustion on a sealed treadmill inhaling an H
2
-containing mixture or the control gas. We measured oxidative stress (SOD, GSH, and TBARS), inflammatory (TNF-α, IL-1β, IL-6, IL-10, and NF-κB phosphorylation), and apoptotic (expression of caspase-3, Bcl-2, and HSP70) markers. Exercise caused no changes in SOD activity but increased TBARS levels. H
2
caused increases in exercise-induced SOD activity and blunted exercise-induced increased TBARS levels. We observed exercise-induced TNF-α and IL-6 surges as well as NF-κB phosphorylation, which were blunted by H
2
. Exercise increased cleaved caspase-3 expression, and H
2
reduced this response. In conclusion, H
2
effectively downregulates muscle damage, reducing oxidative stress, inflammation, and apoptosis after acute exhaustive exercise performed by an unaccustomed organism.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The mechanisms involved in hypothermia and fever during systemic inflammation (SI) remain largely unknown. Our data support the contention that brain-mediated mechanisms are different in hypertension ...during SI. Considering that, clinically, it is not easy to assess all mechanisms involved in cardiovascular and thermoregulatory control during SI, the present study sheds light on these integrated mechanisms that may be triggered simultaneously in septic hypertensive patients. The result obtained demonstrate that, in lipopolysaccharide-induced SI, an increased hypothermia is observed in neurogenic hypertension, which is caused by reduced hypothalamic prostaglandin E
production and increased heat loss in conscious rats. Therefore, the results of the present study provide useful insight for clinical trials evaluating the thermoregulatory outcomes of septic patients with hypertension.
Hypertension is a prevalent disease characterized by autonomic-induced elevated and sustained blood pressure levels and abnormal body core temperature (Tb) regulation. The present study aimed to determine the brain-mediated mechanisms involved in the thermoregulatory changes observed during lipopolysaccharide (LPS)-induced systemic inflammation (SI; at a septic-like model) in spontaneously hypertensive rats (SHR). We combined Tb and skin temperature (Tsk) analysis, assessment of prostaglandin (PG) E
levels (the proximal mediator of fever) in the anteroventral region of the hypothalamus (AVPO; an important site for Tb control), oxygen consumption analysis, cardiovascular recordings, assays of inflammatory markers, and evaluation of oxidative stress in the plasma and brain of male Wistar rats and SHR that had received LPS (1.5 mg kg
) or saline. LPS induced hypothermia followed by fever in Wistar rats, whereas, in SHR, a maintained hypothermia without fever were observed. These thermoregulatory responses were associated with an increased heat loss in SHR compared to Wistar rats. We measured LPS-induced increased PGE
levels in the AVPO in Wistar rats, but not in SHR. The LPS-induced drop in blood pressure was higher in SHR than in Wistar rats. Furthermore, LPS-induced plasma and brain regions involved in autonomic control: nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) cytokine surges were blunted, whereas oxidative stress was higher in SHR. LPS-induced SI leads to blunted cytokine surges both systemically (plasma) and centrally (NTS and RVLM) and reduced hypothalamic PGE
production, which are all associated with increased hypothermia mediated by increased heat loss, but not by heat production, in SHR.
Intermittent fasting (IF) is a dietary approach that is widely popular due to its effects on weight and body fat loss, but it does not appear to ensure muscle mass preservation. Incorporating ...high-intensity interval training (HIIT) into an individual's routine could be an attractive and viable therapeutic option for improving body composition, lifestyle and health promotion. Problematizing the emerging situation of fighting obesity, led us to clarify gaps about IF and hypothesize that IF and HIIT in conjunction may protect against muscle mass decline without impairing nitrogen balance (NB), in addition to improving the physical fitness of women with obesity.
To evaluate the effects of IF alone and combined with HIIT on body composition, NB and strength and physical fitness in women with obesity.
Thirty-six women (BMI 34.0 ± 3.2; 32.2 ± 4.4 years) participated and were randomly distributed into three groups: (1) Intermittent fasting combined with exercise group (IF + EX); (2) Exercise group (EX); and (3) Intermittent fasting group (IF). The interventions took place over 8 weeks and all evaluations were performed pre and post-intervention. The HIIT circuit was performed 3x/week, for 25 mins/session, at 70-85% of the maximum heart rate. The intermittent fasting protocol was a 5:2 diet with two meals within 6 h on fasting days, being 25% of total energy intake, plus 18 h of complete fasting. The protocol was performed 2x/week and 5 days of
ingestion. Resting metabolic rate (RMR) was measured by indirect calorimetry, body composition by BodPod
, NB from urinary nitrogen, food consumption by food records and physical and strength performance were measured by physical tests. ANOVA two-way repeated measures mixed model was performed followed by Sidak
(
< 0.05). This project was registered in ClinicalTrials.gov, NCT05237154.
There were a reduction in body weight (
= 0.012) and BMI (
= 0.031) only in the IF + EX group. There was body fat loss in the IF + EX group (-4%,
< 0.001) and in the EX group (-2.3%,
= 0.043), an increase in fat-free mass in the IF + EX group (+3.3%,
< 0.001) and also in the EX group (+2%,
= 0.043), without differences between groups and the IF group showed no changes. The NB was equilibrium in all groups. All parameters of aerobic capacity and strength improved.
Combining IF with HIIT can promote increments in fat-free mass, NB equilibrium and improve physical fitness and strength.
Regular endurance exercise is a non‐pharmacological strategy to protect the liver against diseases. Conversely, exercise may be harmful when excessive, the so‐called overtraining. As expected, mice ...who underwent an overtraining protocol presented higher levels of proinflammatory cytokines in the serum and liver. Based on the relationship among overtraining, inflammation and mammalian target of rapamycin complex 1 (mTORC1) upregulation, the present study verified if animals submitted to an overtraining protocol, but with inhibition of the mTOR pathway via rapamycin injections could mitigate the liver and serum inflammation. Once autophagy can be linked to the improvement of hepatic dysfunction, we also investigated if the inhibition of mTORC1 by rapamycin can improve hepatic autophagy. The animals were randomized into four groups: control (CT; sedentary mice), overtraining by downhill running (OT; mice submitted to the downhill running‐based overtraining protocol), overtraining by downhill running with chronic administration of rapamycin (OT/Rapa; mice submitted to the downhill running‐based overtraining protocol with intraperitoneal injections of rapamycin) and aerobic (AER; submitted to aerobic training protocol). The serum and liver of the animals were used for biochemical analysis, reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and immunoblotting. The main results are (a) OT and OT/Rapa protocols decreased the performance; (b) the protein levels of interleukin 6 (IL‐6) were higher for the OT group; the OT/Rapa group reduced the autophagic genes, increased the microtubule‐associated protein light chain 3 II/I (LC3II/LC3I) protein ratio and decreased the sequestosome 1 (SQSTM1) protein. In conclusion, rapamycin appears efficiently to increase the autophagy proteins and decrease IL‐6 protein in the liver of overtraining mice.
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