The Role of Piromelatine on Peripheral and Hippocampal Insulin Resistance in Rat Offspring Exposed to Chronic Maternal Stress.

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth. Vehicle or Pir 20 mg/kg were administered intraperitoneally for 21 days. Plasma glucose, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) were determined as markers of peripheral IR. For the hippocampal IR assessment, insulin receptors (IRs) and glucose transporter 4 (GLUT4) were examined. Prenatally stressed offspring of both sexes indicated enhanced plasma glucose and serum insulin concentrations, increased HOMA-IR, and decreased hippocampal GLUT4 only in male rats. The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring.

Modulation of the Cardiovascular Risk in Type 1 Diabetic Rats by Endurance Training in Combination with the Prebiotic Xylooligosaccharide.

Diabetic cardiomyopathy is a major etiological factor in heart failure in diabetic patients, characterized by mitochondrial oxidative metabolism dysfunction, myocardial fibrosis, and marked glycogen elevation. The aim of the present study is to evaluate the effect of endurance training and prebiotic xylooligosaccharide (XOS) on the activity of key oxidative enzymes, myocardial collagen, and glycogen distribution as well as some serum biochemical risk markers in streptozotocin-induced type 1 diabetic rats. Male Wistar rats (n = 36) were divided into four diabetic groups (n = 9): sedentary diabetic rats on a normal diet (SDN), trained diabetic rats on a normal diet (TDN), trained diabetic rats on a normal diet with an XOS supplement (TD-XOS), and sedentary diabetic rats with an XOS supplement (SD-XOS). The results show that aerobic training managed to increase the enzyme activity of respiratory Complex I and II and the lactate dehydrogenase in the cardiomyocytes of the diabetic rats. Furthermore, the combination of exercise and XOS significantly decreased the collagen and glycogen content. No significant effects on blood pressure, heart rate or markers of inflammation were detected. These results demonstrate the beneficial effects of exercise, alone or in combination with XOS, on the cardiac mitochondrial enzymology and histopathology of diabetic rats.

Pre- and Post-Endurance Training Mitigates the Rat Pilocarpine-Induced Status Epilepticus and Epileptogenesis-Associated Deleterious Consequences.

Epilepsy is a brain disorder characterized by recurrent epileptic seizures and neurobiological, physiological, mood, and cognitive consequences. In the last decade, the beneficial effects of regular physical exercise have been investigated in patients with neurodegenerative diseases such as epilepsy. However, data on its beneficial effects and underlying mechanisms are still insufficient. The objective of the current study was to investigate the effects of endurance training, applied before and after pilocarpine (Pilo) administration, on status epilepticus (SE) severity, and its relation to epileptogenesis deleterious consequences during the chronic epileptic phase. Long-term aerobic training, applied four weeks before SE and eight weeks after SE, elevated the threshold to induce SE and reduced spontaneous motor seizures. The protective effect of this alternative approach on seizure susceptibility resulted in improved memory responses, and alleviated comorbid depression in epileptic rats. The exercised epileptic rats had improved markers of oxidative stress by decreasing lipid peroxidation and increasing the levels of glutathione and activity of superoxide dismutase in the rat hippocampus. Aerobic training managed to ameliorate the neuroinflammation by decreasing the levels of TNF-α and IL-1ß in the hippocampus. Our results suggest that regular physical training predisposes the subjects to crucial plastic changes, leading to increased resistance to SE and the development of epileptogenesis.

Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation.

BACKGROUND: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. METHODS: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. RESULTS: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1ß levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.

Effect of Training at Lactate Threshold Intensity on Maximal Time to Exhaustion, Depression and Anxiety Behaviour of Spontaneously Hypertensive Rats after Kainate-Induced Status Epilepticus.

AIM: The objective of the present study was to investigate the effect of treadmill training at lactate threshold intensity on maximum time to exhaustion (MTE) and heart rate (HR) as well as behavioral changes after kainate (KA)-induced status epilepticus (SE) of spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS: Male SHRs were divided in four groups: two sedentary (vehicle- and KA-treated) and two exercised (vehicle- and KA-treated), respectively. The exercised rats were trained on a treadmill at a speed of 20 m.min-1 and 0° elevation for 40 min.d-1, for 4 wk. Maximal time to exhaustion and HR was measured at the beginning and at the end of the training period. Status epilepticus was evoked in half of the sedentary and trained rats by a repetitive intraperitoneal injection of KA in low subconvulsive doses. The other half of the groups received saline. Sucrose preference test (SPT) for depression-like behavior and hole board test (HBT) for impulsivity were performed a month after KA/veh injection. RESULTS: The maximum time of exhaustion was elongated in the SHRs at the end of the training period in comparison with the beginning. However, no effect on HR was detected in trained rats. Kainate treatment after one month of training alleviated the SE-induced anhedonia in SPT and stereotyped behavior in HBT, respectively. CONCLUSIONS: Taken together, these results demonstrate that exercise exerts a beneficial influence on physical working capacity, depression and impulsive behavior in a co-morbid model of essential hypertension and SE.

Ostarine blunts the effect of endurance training on submaximal endurance in rats.

The purpose of this study is to study the effects of ostarine alone and in combination with endurance training in sexually mature, male Wistar rats. The rats were divided into a treadmill-trained group and a sedentary group. Half of each group received either ostarine or vehicle for 8 weeks (n = 10 each, in total n = 40). We examined some functional, hormonal, and anthropometric parameters and the myogenic gene expression of myostatin, insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor-A (VEGF-A) in m. gastrocnemius. Ostarine decreased submaximal endurance and increased myogenic gene expression of myostatin but had no effect on maximal time to exhaustion and grip strength. Training increased submaximal endurance, maximal time to exhaustion, and grip strength. Our results indicate that both exercise and ostarine treatment had no significant effects on serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone, or on the myogenic gene expression of IGF-1 and VEGF-A. Neither ostarine nor the training had a significant effect on the testis, liver, and heart weights. In conclusion, ostarine had no effect on anthropometric and hormonal parameters but increased the myostatin gene expression in muscle. The SARM treatment decreased submaximal endurance without affecting maximal time to exhaustion, and training increased both metrics.

Diet-Induced Early Inflammatory Response of Visceral Adipose Tissue in Healthy Male Wistar Rats.

The prolonged consumption of a high-fat diet (HFD) leads to abnormal growth of the visceral adipose tissue (VAT), increased macrophage infiltration, and altered secretion of biologically active molecules. This is considered as a precondition for the development of obesity, inflammation, and obesity-related disorders. Therefore, we studied HFD-induced changes in the tissue levels of the inflammatory markers C-reactive protein, serum amyloid-A, and interleukin-4 in healthy male Wistar rats. The animals were first divided at random into two groups subjected to either a standard or a high-fat diet. The initial effect of the diet was evaluated after fourteen weeks. In order to study the diet duration effect, the standard diet was given to twelve animals from the HFD group, while the remaining continued with the HFD for an additional four weeks. Our results showed that the HFD barely affected body mass index, conicity, relative fat mass, and Lee indices, whereas it provoked adipocyte hypertrophy and gradually increased the levels of both the pro- and anti-inflammatory markers. The switch from the high-fat to the standard diet resulted in the comparatively fast restoration of the baseline levels of the studied molecules. Although, the prolonged consumption of an HFD causes adipocyte hypertrophy in healthy male animals, the inflammatory process in VAT is well-coordinated, time-dependent, and reversible.

Selective Androgen Receptor Modulators Combined with Treadmill Exercise Have No Bone Benefit in Healthy Adult Rats.

The effects of combination treatments using the selective androgen receptor modulators (SARMs) ostarine (OST) or ligandrol (LIG) with treadmill exercise (TE) were studied in healthy adult rats. Fifteen-week-old male Wistar rats were divided into groups (n = 10/group). Experiment 1 consisted of (1) Control group: sedentary rats receiving vehicle; (2) OST: sedentary rats receiving OST; (3) TE: training rats receiving vehicle; (4) OST + TE: training rats receiving OST. Experiment 2 consisted of (1) LIG: sedentary group receiving LIG; (2) LIG + TE: training group receiving LIG. The TE regime was as follows: 25 m/min, 5° elevation, 40 min, five times/week, and the sedentary regime was 5 min, three times/week. OST and LIG were administered subcutaneously (0.4 mg/kg body weight/day, five times/week). After eight weeks, bone samples underwent microcomputed tomographical, biomechanical, histological, and ashing analyses. All the treatments had weak effects on the bone structure without affecting bone biomechanics. The OST + TE improved bone structure, while the LIG + TE had unfavorable effects. In serum, OST, OST + TE, and LIG + TE altered cholesterol and lipoprotein levels; TE did not change the serum parameters. The SARM treatments had no clear bone benefit, and the serum effects can be considered as side effects. TE represents a safe treatment. Because SARMs are increasingly applied in gyms along with physical activities, attention should be paid to possible side effects.

Metabolic footprint in young, middle-aged and elderly rats with melatonin deficit.

The pineal gland is suggested to be an essential area involved in the programming of fertility, growth, aging, and death of mammals via the released hormone melatonin.The present study aimed to ascertain the effect of melatonin deficit on several physiological and metabolic parameters, closely associated with the aging process, at certain stages of ontogenesis. Sham and rats with pinealectomy, operated at ages 3, 14, and 18-months, respectively, were tested two months later. Sham rats demonstrated an age-related decline of muscle strength, exercise endurance, motor activity, food intake, calorimetric parameters, and impaired lipid profile. Pinealectomy reduced the maximal time to exhaustion and body weight gain while diminished motor activity, food intake, O2 consumption, CO2 production, and energy expenditure during the Dark phase in the youngest rat group. In addition, melatonin deficit elevated arterial blood pressure (systolic, diastolic, and mean arterial pressure) and increased serum glucose and triglyceride level in 3-month-old rats while decreased the liver enzyme activity in 14-month-old rats. In conclusion, the present study brought new insights confirming the complex impact of melatonin deficit on important physiological, metabolic and biochemical markers related to aging and demonstrated for the first time that the lack of melatonin hormone is harmful in young adult rats.

Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes.

Type 1 diabetes mellitus is characterized with decreased microbial diversity. Gut microbiota is essential for the normal physiological functioning of many organs, especially the brain. Prebiotics are selectively fermentable oligosaccharides [xylooligosaccharides (XOS), galactooligosaccharides, etc.] that promote the growth and activity of gut microbes and influence the gut-brain axis. Aerobic exercise is a non-pharmacological approach for the control of diabetes and could improve cognitive functions. The potential beneficial effect of XOS and/or aerobic training on cognition, the lipid profile and oxidative stress markers of experimental rats were evaluated in this study. Male Wistar rats were randomly divided into three streptozotocin-induced diabetic groups and a control group. Some of the rats, either on a XOS treatment or a standard diet, underwent aerobic training. The results showed that the aerobic training independently lowered the total cholesterol levels compared to the sedentary diabetic rats (p = 0.032), while XOS lowers the malondialdehyde levels in the trained diabetic rats (p = 0.034). What is more the exercise, independently or in combination with XOS beneficially affected all parameters of the behavioral tests. We conclude that aerobic exercises alone or in a combination with the prebiotic XOS could ameliorate the dyslipidemia, oxidative stress, and cognitive abilities in experimental type 1 diabetic animals.

Effect of oligosaccharides on the antioxidant, lipid and inflammatory profiles of rats with streptozotocin-induced diabetes mellitus.

Prebiotics, gut microbiota-fermentable substances, delay the development of type I diabetes. In the present study, we investigated the effect of two prebiotics (galacto-oligosaccharides and xylo-oligosaccharides) on the antioxidant protection, lipid profile, and inflammatory activity of rats with streptozotocin-induced diabetes. The following markers were studied - malondialdehyde, 8-hydroxy-2'-deoxyguanosine, ferric reducing ability of plasma (FRAP), triacylglycerols, total cholesterol (TC), high-density lipoproteins, C-reactive protein (CRP), and interleukin-6. Diabetes was induced in male Wistar experimental rats by streptozotocin injection, while the non-diabetic controls were injected with saline. Afterward the oligosaccharides were administered orally to the experimental animals. The blood collected following the decapitation was analyzed by ELISA. A modified protocol was used only for measuring the FRAP values. The galacto-oligosaccharides and xylo-oligosaccharides lowered the malondialdehyde levels in the diabetic rats (p < 0.05). The galacto-oligosaccharides decreased the serum levels of 8-hydroxy-2'-deoxyguanosine (p = 0.01), while the xylo-oligosaccharides increased the FRAP (p < 0.05) in the experimental animals. None of the oligosaccharides affected triacylglycerol and interleukin-6 concentrations, but the galacto-oligosaccharides decreased the TC and CRP levels in the diabetic animals. Both oligosaccharides exert a beneficial effect on the antioxidant protection of the diabetic rats, but have a minor effect on their lipid and inflammatory profiles.

The Effect of Chronic Treatment with Lacosamide and Topiramate on Cognitive Functions and Impaired Emotional Responses in a Pilocarpine-induced Post-status Epilepticus Rat Model.

INTRODUCTION: Epilepsy and antiepileptic drugs can affect negatively the cognitive abilities of patients. AIM: The present study aimed to evaluate the effect of topiramate (TPM) and lacosamide (LCM) on the emotional and cognitive re-sponses in naive animals and in animals with pilocarpine-induced status epilepticus. MATERIALS AND METHODS: Male Wistar rats were randomly divided into 6 groups and status epilepticus was evoked in half of them by a single i.p. administration of pilocarpine (Pilo) (320 mg/kg): Pilo-veh, Pilo-TPM (80 mg/kg) and Pilo-LCM (30 mg/kg). Matched naive rats were treated with the same doses as follows: C-veh, C-TPM, and C-LCM. In a step-down passive avoidance test, the learning session was held for one day, the early retention test was conducted on day 2, and the long-term memory test - on day 7. Motor activity and anxiety were evaluated in an open field test. RESULTS: The Pilo-TPM and Pilo-LCM groups increased the time spent on the platform compared to Pilo-veh animals while the C-LCM animals decreased the time compared to C-veh animals during short- and long-term memory retention tests. TPM and LCM exerted an anxiolytic effect in naive rats. The two antiepileptic drugs were unable to alleviate the hyperactivity, but they alleviated the impulsivity associated with decreased anxiety level in epileptic rats. CONCLUSIONS: Our findings suggest that LCM and TPM have a beneficial effect on cognition both in naive and epileptic rats. While the two antiepileptic drugs can produce an anxiolytic effect in naive rats, they alleviate the impulsivity after pilocarpine treatment.

Endurance training exerts time-dependent modulation on depressive responses and circadian rhythms of corticosterone and BDNF in the rats with pinealectomy.

Pinealectomy can cause a disturbance in emotional status and circadian rhythms of the endocrine and metabolic functions in the body. Endurance training is considered a part of the complex therapy of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we aimed to study the effect of endurance training on depressive behavior induced by pinealectomy in rat. We tested the hypothesis that endurance training can have a beneficial impact on depressive behavior induced by pinealectomy in rat via correction of desynchronized circadian rhythms of corticosterone secretion in plasma and brain-derived neurothrophic factor (BDNF) in the hippocampus. The continuous exercise program attenuated depressive responses characterized by the disrupted diurnal rhythm of home-cage motor activity, anhedonia in the sucrose preference test, decreased grooming in the splash test, and despair-like behavior in the forced swimming test of rats with pinealectomy to values resembling those of sham-treated controls. Parallel to the observed positive effect on the emotional status, exercise training diminished total plasma corticosterone levels and corrected its flattened pattern. While the melatonin deficiency did not affect the fluctuations of the BDNF levels, the exercise program induced a considerable and time-dependent increase in its level. These findings suggest that the antidepressant-like effect of endurance training might be mediated via correction of the disturbed circadian rhythm of corticosterone release and enhancement of hippocampal BDNF levels in rats with pinealectomy. Therefore, this alternative mode might have a potential therapeutic application in a subpopulation of people characterized by a melatonin deficiency.

Enhancing effect of aerobic training on learning and memory performance in rats after long-term treatment with Lacosamide via BDNF-TrkB signaling pathway.

Aerobic training has a neuroprotective effect, reduces the risk of developing neurodegenerative diseases and facilitates functional recovery. The present study assesses the effect of aerobic training on cognitive functions, hippocampal BDNF/TrkB ligand receptor system expression and serum levels of BDNF and corticosterone in intact rats after chronic treatment with Lacosamide (LCM). Male Wistar rats were randomly divided into two groups. One group was exercised on a treadmill (Ex) and the other one was sedentary (Sed). Half of the rats from each group received saline (veh) while the other half - LCM. The rats underwent a month-long training and LCM treatment before being subjected to one active and two passive avoidance tests. Both trained groups increased significantly the number of avoidances compared with the sedentary animals during the learning session and on memory retention tests, while the number of avoidances of the LCM-treated rats was significantly lower in comparison with the saline-treated animals. Both passive avoidance tests revealed that trained animals spent more time in the lighted compartment or caused longer stay on the platform than did the sedentary rats during acquisition and short- and long-term memory retention tests. Aerobic training increased BDNF and TrkB hippocampal immunoreactivity. We found no significant difference between BDNF serum levels but corticosterone levels of the Sed-LCM rats were lower than those of the Sed-veh animals. Our results show that aerobic training increases the hippocampal BDNF/TrkB expression suggesting a role in preventing the negative effect of Lacosamide on cognitive functions in rats.

Impact of a High-fat Diet on the Development of Chronic Inflammation in Heart of Wistar rats.

INTRODUCTION: Obesity is linked to the development of low-grade, chronic inflammation. Obesity-related inflammation appears to be a different type of inflammation, mainly due to excessive food intake and unusual homeostasis. It can be evaluated by measuring the concentration of pro- and anti-inflammatory marker molecules ­ C-reactive protein (CRP), serum amyloid-A (SAA) and interleukin-4. AIM: The aim of the present study is to evaluate the rate of the inflammatory process in heart, provoked by the consumption of a high-fat diet. MATERIALS AND METHODS: Sixty 8-week-old male Wistar rats were used in this experiment. The laboratory animals were fed orally with two different types of rodent food for 14 or 18 weeks ­ a high-fat diet (experimental groups) and standard rodent food (control groups). They all were kept under standard housing conditions. The levels of the pro- and anti-inflammatory markers in tissue homogenates from heart were analyzed using ELISA. Their expression in tissue samples was detected immunohistochemically by the biotin-streptavidin-peroxidase method. The total protein concentration was determined by the Lawry method. RESULTS: CRP levels showed no significant differences when the control group was compared with the groups fed with a high-fat diet (p>0.05). The SAA levels detected were also insignificantly changed. Only the IL-4 tissue levels showed tendency to increase (p<0.05) in the high-fat diet group. CONCLUSIONS: Our experiment indicates that there is a specific reaction of the heart to a high-fat diet. It also refers to the existence of adaptive mechanisms allowing the heart to counteract the development of dietary induced inflammation.

Health status of Pelophylax ridibundus (Amphibia: Ranidae) in a rice paddy ecosystem in Southern Bulgaria and its importance in assessing environmental state: haematological parameters.

Pollution effects on haematological parameters in Pelophylax ridibundus individuals were investigated; animals were collected from two sites in Southern Bulgaria: the Tsalapitsa rice fields (RF) and the Vacha river (reference site, RS). Blood analysis showed significant differences between the haematological parameters of RBC, WBC, Hb, packed cell volume (PCV) and frogs' leucogram from RF and those from RS. These findings provide information on long-term background pollution of the habitat (RF) under investigation. In our view, the erythropenia, leucopenia, hypоchromia, lower values of PCV, St-neutrophilia, Sg-neutropenia, basopenia, eosinophilia, monocytosis and lymphopenia that were found in Pelophylax ridibundus individuals inhabiting the Tsalapitsa rice fields were probably caused by the pesticides and fertilizers that enter the paddy cages during the rice production process. The present study proves the practical usefulness of haematological parameters of Pelophylax ridibundus individuals in bioindication analyses for environmental assessment of agroecosystems.

Chronic treatment with the new anticonvulsant drug lacosamide impairs learning and memory processes in rats: A possible role of BDNF/TrkB ligand receptor system.

Cognitive impairment is considered a frequent side effect in the drug treatment of epilepsy. The objective of the present study was to investigate the effects of lacosamide (LCM) on learning and memory processes in rats, on the serum level of brain-derived neurotrophic factor (BDNF) and BDNF/TrkB ligand receptor system expression in the hippocampal formation. Male Wistar rats underwent long-term treatment with three different doses of lacosamide - 3 mg/kg (LCM 3), 10 mg/kg (LCM 10) and 30 mg/kg (LCM 30). All rats were subjected to one active and one passive avoidance tests. The BDNF/TrkB immunohistochemical expression in the hippocampus was measured and serum BDNF was determined. The LCM-treated rats made fewer avoidance responses than controls during acquisition training and in the memory retention test. The number of escapes in the LCM 10 and LCM 30 groups decreased throughout the test, while the rats in the LCM 3 group showed fewer escapes only in the memory test in the active avoidance task. In the step-down test, the latency time of the LCM-30 treated rats was reduced as compared with the controls during the learning session and the short- and long-term memory retention tests. Lacosamide induced a dose-dependent reduction of the hippocampal expression of BDNF and its receptor TrkB. We found no significant difference between BDNF serum levels in the test animals and controls. The results of the study suggest that LCM suppresses the learning and memory processes in rats, with the inhibition of hippocampal BDNF/TrkB ligand receptor system being one of the possible mechanisms causing this effect.

The effect of flutamide on the physical working capacity and activity of some of the key enzymes for the energy supply in adult rats.

The aim of the study was to assess the effects of androgen receptor antagonists on the physical working capacity and activity of some of the key muscle enzymes for the energy supply in rats. Young adult male Wistar rats were divided into two groups. One group received 15 mg kg-1 of flutamide daily for 6 days a week and the other group served as control for 8 weeks. At the beginning and at the end of the experiment, all rats were subjected to submaximal running endurance (SRE), maximum time to exhaustion (MTE), and maximal sprinting speed (MSS) tests. At the end of the trial, maximum oxygen consumption (VO2max) test was performed and the levels of testosterone, erythrocytes, hemoglobin as well as enzyme activity of succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), and NAD.H2-cytochrome-c reductase (NAD.H2) of the gastrocnemius muscle were measured. Serum testosterone of the flutamide-treated rats was higher than that of the controls, which verifies the effectiveness of the dose chosen. MTE and SRE of the anti-androgen-treated group were lower compared with the initial values. Flutamide treatment decreased the activity of SDH and NAD.H2 compared with the controls. We found no effect of the anti-androgen treatment on MSS, VO2max, running economy, LDH activity, and hematological variables. Our findings indicate that the maintenance of the submaximal and maximal running endurance as well as the activity of some of the key enzymes associated with muscle oxidative capacity is connected with androgen effects mediated by androgen receptors.

Bcl-2/Bax ratio, mitochondrial membranes and aerobic enzyme activity in cardiomyocytes of rats after submaximal training.

INTRODUCTION: Mitochondria are an active and continuous source of reactive oxygen species (ROS) during respiration. The ROS increased production during endurance training is a result of an augmented electron transport through the respiratory chains, making in this way the mitochondria a potential target for oxidative damage. The Bcl-2 protein family plays a central role in the transition of apoptotic signals towards the mitochondria in stress-induced apoptosis. AIM: The present work studied the effect of endurance training on the expression of the apoptotic proteins Bcl-2 and Bax in rat cardiomyocytes, as well as the concomitant changes in the ultrastructure of the mitochondria and activity of some enzymes residing there. MATERIAL AND METHODS: Two groups of male Wistar rats were used. One was the control and the other was trained on treadmill with submaximal loading for eight weeks. At the end of the trial, samples of the myocardium of all the experimental animals were obtained. Immunohistochemical reactions for Bcl-2 and Bax and enzymehistochemical reactions for succinate dehydrogenase and NADH2-cytochrome C-reductase were done. The results were analyzed using specialized software. Transmission electron microscopical study was carried out too. RESULTS: In the myocardium of the trained animals the expression of Bcl-2 and Bcl-2/Bax ratio were significantly higher compared to the controls. The mitochondria had intact outer and inner membranes, with no signs of swelling. Mitochondria with denser packed cristae were found predominantly. No significant differences were found in the activity of the investigated enzymes in the cardiomyocytes of the animals from both groups. CONCLUSIONS: In the myocardium of the experimental animals endurance training for eight weeks does not lead to activation of apoptotic processes via the mitochondrial pathway. This type of exercise training could be used for cardioprotection in order to elevate apoptotic threshold of cardiomyocytes.

Effects of nandrolone decanoate on VO2max, running economy, and endurance in rats.

PURPOSE: The aim of the present study was to determine the effects of treatment with an anabolic androgenic steroid (AAS), nandrolone decanoate, on the submaximal running endurance (SRE), maximum oxygen consumption (VO2max), running economy (VO2submax), and blood oxygen carrying capacity of endurance trained rats. METHODS: Forty male Wistar rats were randomly allocated into two groups: a sedentary group and an exercising group training on treadmill for 8 wk. Half of the trained and half of the sedentary rats received weekly either nandrolone decanoate (10 mg x kg(-1)) or placebo (Pl) for the last 6 wk of experiment. SRE and VO2max tests were performed several times for all four groups (N = 10 each).Red blood cells parameters were measured at the end of the experiment. RESULTS: The trained rats had increased their SRE compared with sedentary rats throughout the experiment. At the end of the trial, the trained rats receiving nandrolone decanoate ran 46% longer than trained rats receiving Pl during the SRE test (P < 0.05). At the end of the experiment, trained rats had greater maximal time to exhaustion and higher VO2max than those of the sedentary rats but there were no differences in VO2max, VO2submax, and red blood cells parameters between the trained rats receiving nandrolone decanoate and those receiving Pl. CONCLUSIONS: Nandrolone decanoate has no effect on the SRE, VO2max and VO2submax of untrained rats. AAS treatment combined with submaximal training enhances SRE more than training alone but exerts no additive effects on VO2max, running economy, and oxygen carrying capacity of blood. The results suggest that this improvement in SRE of trained rats is due to the impact of AAS on other factors involved in exercise adaptation.