Redox status biomarkers in the fast-twitch extensor digitorum longus resulting from the hypoxic exercise.

The fast-twitch muscle may be affected from over-produced reactive oxygen species (ROS) during hypoxia/hypoxic exercise. The study aims to investigate redox status biomarkers in the fast-twitch extensor digitorum longus (EDL) muscle after hypoxic exercise. Male Sprague Dawley rats (eight-week-old) were randomly divided into six groups of the experimental "live high train high (LHTH), live high train low (LHTL) and live low train low (LLTL)" and their respective controls. Before the EDLs' extraction, the animals exercised for a 4-week familiarization period, then they exercised for four-weeks at different altitudes. The LHTH group had higher ratios of lipid hydroperoxides (LHPs) than the experimental groups of LHTL (p=0.004) and LLTL (p=0.002), while having no difference than its control 'LH'. Similarly, a higher percentage of advanced oxidation protein products (AOPP) was determined in the LHTH than the LHTL (p=0.041) and LLTL (p=0.048). Furthermore, oxidation of thiol fractions was the lowest in the LHTH and LH. However, redox biomarkers and thiol fractions illustrated no significant change in the LHTL and LLTL that might ensure redox homeostasis due to higher oxygen consumption. The study shows that not hypoxic exercise/exercise, but hypoxia might itself lead to a redox imbalance in the fast-twitch EDL muscle.

Possible Adaptation of the Adrenal Gland Hsp72 Expression to Hypoxic Stress.

Akin, Senay, Metin Bastug, Ridvan Colak, Hakan Ficicilar, Betul Simten Saglam, Nazan S. Kosar, and Haydar Demirel. Possible adaptation of the adrenal gland Hsp72 expression to hypoxic stress. High Alt Med Biol. 22:293-299, 2021. Background: Adrenal glands play a central role in the general response to stress and controlling wholebody homeostasis. One of the most severe environmental stresses encountered by high-altitude climbers is hypoxia. Since the 72 kDa heat shock protein (Hsp72) has a critical role in cellular homeostasis, regulation of Hsp72 in adrenal glands seems to be crucial for maintaining cellular integrity of the gland and sustaining an adequate whole-body stress response in a hypoxic environment. Therefore, this study investigated if 15 days of hypoxia results in the induction of Hsp72 in adrenal glands. In addition, we examined whether heat treatment had any effect on adrenal Hsp72 expression to hypoxia, as cellular and systemic physiological cross-adaptation was suggested between heat stress and hypoxic stress. Materials and Methods: Male 4-month-old Wistar rats were randomly assigned to one of the four experimental groups (n = 8 each group): (1) control (C), (2) heat treatment (15H), (3) heat treatment and 15 days of normobaric hypoxia (15HHp), and (4) 15 days of normobaric hypoxia (15Hp). Three one-hour heat treatment sessions at 41°C were applied on the first two days before hypoxic exposure and on the day 7. Hypoxic exposure was consisting of normobaric hypoxia containing 9.7% O2. Results: Fifteen days of hypoxia did not increase the adrenal Hsp72 levels (p = 0.99). Furthermore, when hypoxia was added to the heat treatment, heat-related increases in adrenal Hsp72 levels disappeared. Adrenal weight to body weight ratio was not different among groups (p = 0.11). Plasma corticosterone levels were significantly lower in all experimental groups compared with control (p < 0.05), and addition of hypoxia resulted in further significant reduction of the plasma corticosterone levels (C > 15H>15HHp >15Hp; p < 0.05). Conclusions: These data demonstrate the adaptation of the adrenal gland to 15-day chronic normobaric hypoxic stress as well as possible cross-adaptation between heat and hypoxic stress in the adrenal gland.

"Live High Train Low" Hypoxic Training Enhances Exercise Performance with Efficient Redox Homeostasis in Rats' Soleus Muscle.

Çolak, Ridvan, Eda Agascioglu, and Ufuk Çakatay. "Live high train low" hypoxic training enhances exercise performance with efficient redox homeostasis in rats' soleus muscle. High Alt Med Biol. 22:77-86, 2021. Background: Different types of hypoxic training have been performed to improve exercise performance. Although both "live high train high" and "live high train low" techniques are commonly performed, it is still obscure as to which one is more beneficial. Materials and Methods: Eight-week-old male Sprague-Dawley rats were randomly divided into aforementioned experimental groups. After a familiarization exercise (4-week, ∼15-30 minutes/day) at normoxia, all rats exercised (4-week, ∼35 minutes/day) at hypoxia with their pre-evaluated maximal aerobic velocity test. The soleus was extracted after the test following 2 days of resting. Results: The live high trained low group displayed better performance than the live high trained high (p = 0.031) and the live low trained low (p = 0.017) groups. Redox status biomarkers were higher in the live high trained high group except for thiols, which were illustrated with no difference among the groups. Further, contrary to total and protein thiols (r = 0.57, p = 0.037; r = 0.55, p = 0.042 respectively), other redox status biomarkers were observed to be negatively correlated to exercise performance. Conclusions: The live high trained low group could consume more oxygen during exercise, which might lead to having a better chance to ensure cellular redox homeostasis. Therefore, this group could ensure an optimum exercise performance and anabolic metabolism.

Impaired redox homeostasis in the heart left ventricles of aged rats experiencing fast-developing severe hypobaric hypoxia.

Despite its rare occurrence, humans and animals have been prone to getting fast developing severe hypobaric hypoxia. Understanding the redox homeostasis related response of an aging heart to this type of hypoxia are crucially important, since the metabolism of myocardial tissue depends on the redox status of proteins. Rodents can tolerate hypoxic stress better than human subjects. This study was aimed at investigating the effects of fast developing severe hypobaric hypoxia on redox status biomarkers; such as, advanced oxidation protein products (AOPP), lipid hydroperoxides (LHPs), protein carbonyl groups (PCO), protein thiol groups (P-SH), and total thiol groups (T-SH) on the myocardial left ventricles of young and aged Wistar rats. The rats were gradually ascended and exposed to an 8000-meter hypobaric hypoxia. While AOPP levels showed no difference, the TSH and PSH concentrations decreased, and the PCO and LHP increased in both of the hypoxic groups than the controls. The TSH and PSH were lower, and AOPP, PCO and LHP were found to be higher in the elderly hypoxic groups than in the young ones. The significant outcome of the study represents that an 8000-meter hypobaric hypoxia could be considered as a severe hypoxic stress, but not life-treating for the rats and would affect both the young and aged left ventricles similarly in respect to impaired redox status. However, if the percentage increases are taken into consideration, it seems that the higher rate of protein oxidation occurs in young hearts; meanwhile aged hearts are more prone to T-SH oxidation.

Altitude training induced alterations in erythrocyte rheological properties: a controlled comparison study in rats.

Altitude training is frequently used by athletes to improve sea-level performance. However, the objective benefits of altitude training are controversial. This study aimed to investigate the possible alterations in hemorheological parameters in response to altitude training. Sprague Dawley rats, were divided into 6 groups: live low-train low (LLTL), live high-train high (LHTH), live high-train low (LHTL) and their controls live high and low (LHALC), live high (LHC), live low (LLC). LHC and LHTH groups were exposed to hypoxia (15% O2, altitudes of 3000 m), 4 weeks. LHALC and LHTL were exposed to 12 hours hypoxia/normoxia per day, 4 weeks. Hypoxia was maintained by a hypoxic tent. The training protocol corresponded to 60-70% of maximal exercise capacity. Rats of training groups ran on treadmill for 20-30 min/day, 4 days/week, 4 weeks. Erythrocyte deformability of LHC group was increased compared to LHALC and LLC. Deformability of LHTH group was higher than LHALC and LLTL groups. No statistically significant alteration in erythrocyte aggregation parameters was observed. There were no significant relationships between RBC deformability and exercise performance. The results of this study show that, living (LHC) and training at altitude (LHTH) seems more advantageous in hemorheological point of view.

Effects of conjugated linoleic acid supplementation and exercise on post-heparin lipoprotein lipase, butyrylcholinesterase, blood lipid profile and glucose metabolism in young men.

This study was designed to investigate the effects of conjugated linoleic acid (CLA) supplementation and endurance exercise training-induced changes on post-heparin lipoprotein lipase (PH-LPL) and butyrylcholinesterase (BChE) activities along with leptin, insulin and lipid levels in plasma by a randomized double blind experiment. Eighteen sedentary male volunteers were randomly divided into CLA and Placebo (PLC) supplementation groups. Both groups underwent daily supplementation of either 3g CLA or 3g placebo for 30 days, respectively, and performed exercise on a bicycle ergometer 3 times per week for 30-40 min at 50% VO2 peak workload. For plasma glucose, insulin and leptin levels and BChE activity fasting blood was used. For PH-LPL measurements, blood was collected 15 min after 50 IU/kg iv heparin injection. In all groups, there is a statistically significant decrease in BChE (p = 0.03, p = 0.02) and leptin (p = 0.002), insulin and HOMA-IR levels (p = 0.02). Exercise with or without CLA supplementation decreased insulin levels and increased insulin sensitivity. PH-LPL activity was increased significantly in both groups, displaying increased fatty acid mobilization. We conclude that though CLA supplementation and exercise can affect these parameters, CLA is not more effective than exercise alone. Hence, a prolonged supplementation regime may be more effective. Taken together in our small study group, our findings display that BChE is a potential marker for synthetic function of liver, fat metabolism, an obesity marker, a function long overlooked.

Exercise and DHA prevent the negative effects of hypoxia on EEG and nerve conduction velocity.

It is known that hypoxia has a negative effect on nervous system functions, but exercise and DHA (docosahexaenoic acid) have positive effect. In this study, it was investigated whether exercise and/or DHA can prevent the effects of hypoxia on EEG and nerve conduction velocity (NCV). 35 adult Wistar albino male rats were divided into five groups (n=7): control (C), hypoxia (H), hypoxia and exercise (HE), hypoxia and DHA (HD), and hypoxia and exercise and DHA (HED) groups. During the 28-day hypoxia exposure, the HE and HED groups of rats were exercised (0% incline, 30 m/min speed, 20 min/day, 5 days a week). In addition, DHA (36 mg/kg/day) was given by oral gavage to rats in the HD and HED groups. While EEG records were taken before and after the experimental period, NCV records were taken after the experimental period from anesthetized rats. Data were analyzed by paired t-test, one-way ANOVA, and post hoc Tukey test. In this study, it was shown that exposure to hypoxia decreased theta activity and NCV, but exercise and DHA reduced the delta activity, while theta, alpha, beta activities, and NCV were increased. These results have shown that the effects of hypoxia exposure on EEG and NCV can be prevented by exercise and/or DHA.