Moderate altitude but not additional endurance training increases markers of oxidative stress in exhaled breath condensate

Oxidative stress occurs at altitude, and physical exertion might enhance this stress. In the present study, we investigated the combined effects of exercise and moderate altitude on redox balance in ten endurance exercising biathletes, and five sedentary volunteers during a 6-week-stay at 2,800 m. As a marker for oxidative stress, hydrogen peroxide (H₂O₂) was analyzed by the biosensor measuring system Ecocheck™, and 8-iso prostaglandin F2α (8-iso PGF2α) was determined by enzyme immunoassay in exhaled breath condensate (EBC). To determine the whole blood antioxidative capacity, we measured reduced glutathione (GSH) enzymatically using Ellman’s reagent. Exercising athletes and sedentary volunteers showed increased levels of oxidative markers at moderate altitude, contrary to our expectations; there was no difference between both groups. Therefore, all subjects’ data were pooled to examine the oxidative stress response exclusively due to altitude exposure. H₂O₂ levels increased at altitude and remained elevated for 3 days after returning to sea level (p ≤ 0.05). On the other hand, 8-iso PGF2α levels showed a tendency to increase at altitude, but declined immediately after returning to sea level (p ≤ 0.001). Hypoxic exposure during the first day at altitude resulted in elevated GSH levels (p ≤ 0.05), that decreased during prolonged sojourn at altitude (p ≤ 0.001). In conclusion, a stay at moderate altitude for up to 6 weeks increases markers of oxidative stress in EBC independent of additional endurance training. Notably, this oxidative stress is still detectable 3 days upon return to sea level.

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The contribution of Max Gassmann and Katja Heinicke who are the senior authors was equivalent.     

红景天苷对急性心肌缺血大鼠心肌细胞凋亡的作用及机制研究

目的：观察红景天苷对急性心肌缺血大鼠心肌细胞凋亡的影响,探讨其可能的分子机制。方法：制备Sprague Dawley大鼠急性心肌缺血模型,随机分为红景天苷高、低剂量组(40 mg/kg、10 mg/kg)、急性心肌缺血组和对照组。原位末端转移酶标记染色法检测心肌组织凋亡情况,免疫印迹法检测心肌组织Bcl-2、Bax、Cytochrome c (Cyt-c)、cleaved caspase-3以及cleaved caspase-9蛋白的表达水平。结果：原位末端转移酶标记染色法显示红景天苷浓度依赖性抑制急性心肌缺血所引起心肌细胞的凋亡;免疫印迹法结果显示,与急性心肌缺血组相比,红景天苷干预后心肌组织中Bcl-2的蛋白表达显著增加,Bax的蛋白表达显著减少,胞浆(cyto)中Cyt-c的蛋白表达水平显著下降,cleaved caspase-3和cleaved caspase-9表达均显著降低。结论：红景天苷具有抗心肌细胞凋亡的作用,其作用机制可能是通过抑制线粒体通路减少细胞的凋亡。本实验为红景天苷可作为临床上治疗缺血性心脏病提供实验依据。     

Effect of anabolic/androgenic steroids on myosin heavy chain expression in hindlimb muscles of male rats

We have examined the effect of male sex hormones on the myosin heavy chain (MHC) expression of the soleus and extensor digitorum longus (EDL) muscles. Young male adult Wistar rats were treated over a 25-day period with either oil (CON, n = 8), nandrolone (nortestosterone decanoate, NAN, n = 8), nandrolone combined with endurance exercise (treadmill running, NAN+EXE, n = 8), or were castrated (CAS, n = 8). The MHC composition of the soleus and EDL muscles was measured by electrophoresis. Castration and treatment with nandrolone had no effect (P > 0.05) on the relative levels of MHC in the soleus and EDL. In contrast, in NAN+EXE rats, the relative level of MHC-1 increased [slow isoform; mean (SD) 97.6 (4.7)% in NAN+EXE rats, versus 86.5 (7.5)% in CON rats] and MHC-2a decreased [fast isoform; 2.4 (4.7)% in NAN+EXE, versus 13.5 (7.5)% in CON rats], only in the soleus (P < 0.05). In conclusion, it appears that endogenous anabolic/androgenic steroids are not essential for the maintenance of the MHC expression of fast- and slow-twitch muscles in the young adult male rat. In addition, nandrolone combined with endurance exercise induced a shift from a fast to a slower MHC phenotype of the slow-twitch muscle. Accepted: 27 July 1999     

Short-term exercise training improves diaphragm antioxidant capacity and endurance

These experiments tested the hypothesis that short-term endurance exercise training would rapidly improve (within 5 days) the diaphragm oxidative/antioxidant capacity and protect the diaphragm against contraction-induced oxidative stress. To test this postulate, male Sprague-Dawley rats (6 weeks old) ran on a motorized treadmill for 5 consecutive days (40–60 min · day⁻¹) at approximately 65% maximal oxygen uptake. Costal diaphragm strips were excised from both sedentary control (CON, n=14) and trained (TR, n=13) animals 24 h after the last exercise session, for measurement of in vitro contraction properties and selected biochemical parameters of oxidative/antioxidant capacity. Training did not alter diaphragm force-frequency characteristics over a full range of submaximal and maximal stimulation frequencies (P > 0.05). In contrast, training improved diaphragm resistance to fatigue as contraction forces were better-maintained by the diaphragms of the TR animals during a submaximal 60-min fatigue protocol (P < 0.05). Following the fatigue protocol, diaphragm strips from the TR animals contained 30% lower concentrations of lipid hydroperoxides compared to CON (P < 0.05). Biochemical analysis revealed that exercise training increased diaphragm oxidative and antioxidant capacity (citrate synthase activity +18%, catalase activity +24%, total superoxide dismutase activity +20%, glutathione concentration +10%) (P < 0.05). These data indicate that short-term exercise training can rapidly elevate oxidative capacity as well as enzymatic and non-enzymatic antioxidant defenses in the diaphragm. Furthermore, this up-regulation in antioxidant defenses would be accompanied by a reduction in contraction-induced lipid peroxidation and an increased fatigue resistance. Accepted: 6 August 1999     

Substrate use and biochemical response to a 3,211-km bicycle tour in trained cyclists

The purpose of this study was to assess the physiological adaptations in physically fit individuals to a period of intensified training. Ten trained males cycled outdoors ~170 km day⁻¹ on 19 out of 21 days. Expired gas was collected on days 1 and 21 during maximal graded exercise and used for the determination of gross efficiency and whole body substrate use. Muscle biopsies were obtained before and after exercise on days 2 and 22 for the determination of mtDNA/gDNA ratio, gene expression, metabolic enzyme activity and glycogen use. Muscle glycogen before and after exercise, fat oxidation, and gross efficiency increased, carbohydrate oxidation decreased (p < 0.05), and VO_2max did not change over the 21 days of training. Citrate synthase (CS), β-hydroxyacyl CoA dehydrogenase (β-HAD) and cytochrome c oxidase (COX) enzyme activity did not change with training. CS and β-HAD mRNA did not change with acute exercise or training. COX (subunit IV) mRNA increased with acute exercise (p < 0.05) but did not change over the 21 days. PGC-1α mRNA increased with acute exercise, but did not increase to the same degree on day 22 as it did on day 2 (p < 0.05). UCP3 mRNA decreased with training (p < 0.05). Acute exercise caused an increase in mitofusin2 (MFN2) mRNA (p < 0.05) and a trend for an increase in mtDNA/gDNA ratio (p = 0.057). However, training did not affect MFN2 mRNA or mtDNA/gDNA ratio. In response to 3,211 km of cycling, changes in substrate use and gross efficiency appear to be more profound than mitochondrial adaptations in trained individuals.     

Bacterial LPS Mediated Acute Inflammation-induced Spermatogenic Failure in Rats: Role of Stress Response Proteins and Mitochondrial Dysfunction

Bacterial Lipopolysaccharide (LPS) induced inflammation is implicated in the infection associated testicular tissue damage. Earlier, using a LPS induced acute endotoxemic rat model, we have shown the involvement of inflammation-induced oxidative stress in the impaired steroidogenesis and spermatogenesis. In the present study, we report a significant induction (more than 2-fold) of stress response proteins HSP-60, HMGB-1 and 2 in the testes, as early as 6 h after LPS injection with a later decrease. This induction of acute stress is closely followed by a significant reduction (74%) in Bcl2/Bax ratio along with leakage of cytochrome c (3 fold increase, p < 0.05) from mitochondria and increased caspase-3 activity levels (2.9 fold, p < 0.05) at 12 h and 24 h post LPS injection respectively. Further studies on PARP cleavage revealed a pattern similar to necrotic death during early periods (3 h to 24 h) and apoptosis at later periods (24 h to 72 h) after LPS treatment. In conclusion, the present study shows the involvement of stress response proteins and mitochondrial dysfunction in LPS-induced germ cell death in male rats.     

Effects of intermittent hypoxia on the cerebrovascular responses to submaximal exercise in humans

Intermittent hypoxia (IH) has been shown to alter the ventilatory and cardiovascular responses to submaximal exercise; however, the effect of IH on the cerebral blood flow (CBF) response to submaximal exercise has not been determined. This study tested the hypothesis that IH would blunt the CBF response during eucapnic and hypercapnic exercise. Nine healthy males underwent 10 consecutive days of isocapnic IH (oxyhaemoglobin saturation = 80%, 1 h day⁻¹). Ventilatory, cardiovascular, and cerebrovascular responses to cycle exercise (50, 100, and 150 W) were measured before and after IH. Carbon dioxide (5% CO₂), a mediator of CBF during exercise, was administered for 2 min of each exercise stage. Over the 10 days of IH, there was an increase in minute ventilation during the IH exposures (P < 0.05). Although exercise produced increases in middle cerebral artery mean velocity (MCA V _mean), and mean arterial pressure (P < 0.05), there was no effect of IH. Similarly, hypercapnic exercise increased and MCA V _mean (P < 0.05); however, the magnitude of the response was unchanged following IH. Our findings indicate that ten daily hypoxia exposures does not alter the CBF response to submaximal exercise.     

Haematological and clinical chemistry findings associated with sub-acute contamination of drinking water with varied low percentages of used engine oil

This study evaluated the haematology and clinical chemistry profile of rats given drinking water contaminated with varied low percentages of used engine oil (UEO) for a period of 21 days. Fifty female albino rats of 6–7 weeks of age were used for the study. They were divided into five groups (A–E) and given water contaminated with 5%, 1%, 0.1%, 0.01% and 0% vol/vol. of UEO respectively as the only source of drinking water for 21 days. The group E given uncontaminated water (0% contamination) served as the control. The haematological parameters and clinical chemistry profile of the rats was comprehensively evaluated after the 21 days of administration of the group-specific waters. Results showed that contamination of water with up to 5% UEO led to no significant effects (p > 0.05) on all the haematological indices and on the levels of serum alanine amino transferase, aspartate amino transferase, albumin, creatinine and calcium, blood urea nitrogen and fasting blood glucose level, feed consumption and body weight. However, the rat group given water contaminated with 5% UEO had a significantly increased serum alkaline phosphatase (AP) (p < 0.01), total bilirubin (p < 0.05) and cholesterol (p < 0.01), and a significantly decreased serum total protein and globulin (p < 0.01), and water consumption (p < 0.05). The rat group given water contaminated with 1% UEO had a significantly increased serum AP (p < 0.01), total bilirubin (p < 0.05) and cholesterol (p < 0.01), and a significantly decreased water consumption (p < 0.05), while the rat group given water contaminated with 0.1% UEO had a significantly elevated (p < 0.01) serum AP. It was concluded that sub-acute contamination of drinking water of rats with up to 5% UEO led to hepato-biliary disorders and adverse effects on hepatic secretion and excretion, including diminution of serum protein and globulin levels and elevation of serum cholesterol levels, but did not lead to any significant effects on haematology, hepatocellular integrity, kidney/renal function, pancreatic function and body weight.     

Endurance training accelerates exhaustive exercise-induced mitochondrial DNA deletion and apoptosis of left ventricle myocardium in rats

Even though exhaustive exercise-induced oxidative stress increases the risk of tissue damage, regular endurance training is widely assumed to improve cardiac function and protects against heart disease. We tested the hypothesis that an endurance training program prevents exhaustive exercise-induced increases in cardiac dysfunction and apoptosis in left ventricle (LV). Thirty-two male Sprague-Dawley rats were randomly divided into four groups: sedentary control (C), trained (T), exhaustively exercised (E), and trained plus exhaustively exercised (TE). Rats in T and TE groups ran on a motorized treadmill for 12 weeks. Rats in groups E and TE performed an exhaustive running test on a treadmill. The main effects of training were indicated by increased running time to exhaustion (80 ± 5 and 151 ± 13 min for groups E and TE, respectively, P = 0.0001), myocardial hypertrophy (0.38% and 0.47% for untrained and trained rats, respectively, P = 0.0002), decreased LV ejection fraction (88% and 71% for untrained and trained rats, respectively, P < 0.0001), accelerated mitochondrial DNA 4834-bp large deletion (mtDNA⁴⁸³⁴ deletion), and up-regulated protein levels of heat shock protein-70, cytochrome C, cleaved capsase-3, and cleaved PARP in LV following a bout of exhaustive exercise. Contrary to our hypothesis, these results suggest that endurance training induced significant impairment of regional systolic and diastolic LV myocardial function and ejection fraction in rats. Our findings show that endurance training accelerates exhaustive exercise-induced mtDNA⁴⁸³⁴ deletion and apoptosis in the LV.     

Postnatal development in intermittent hypoxia enhances resistance to myocardial ischemia/reperfusion in male rats

To assess the tolerance of rats that developed from birth in intermittent hypoxia (IH) to myocardial ischemia and reperfusion, we set up a reproducible model in our laboratory. IH rats were raised 60 days from birth in a hypobaric chamber at 5000 m for 6 h daily, while controls were in continuous normoxic conditions. At 60 days after birth, the antioxidant capacity of the heart was determined; arterial and venous partial pressures of oxygen were measured at sea level and 5000 m altitude. In addition, isolated hearts of each group were perfused in Langendorff mode and submitted to 30 min global ischemia followed by 30 min reperfusion to compare functional recovery and lactate dehydrogenase release. For the IH rats, recovery of left ventricular developed pressure (DP), the maximum of the positive or negative first derivative of left ventricular pressure with respect to time (±LV dP/dt), end-diastolic pressure (EDP), and pressure-rate product (PRP) were all superior (P<0.05) to those of control rats. The myocardial antioxidant capacity was also significantly increased in the left ventricle of IH rats. Further, at 5000 m altitude the arterio-venous oxygen gradient (Pa–vO₂) was significantly (P<0.01) higher in the IH rats than in the controls. These data indicate that IH from birth enhances the tolerance of the heart to ischemia/reperfusion, elevates the myocardial antioxidant capacity, and increases oxygen extraction.     

The effects of running exercise on oxidative capacity and PGC-1α mRNA levels in the soleus muscle of rats with metabolic syndrome

Skeletal muscles in animals with metabolic syndrome exhibit reduced oxidative capacity. We investigated the effects of running exercise on fiber characteristics, oxidative capacity, and mRNA levels in the soleus muscles of rats with metabolic syndrome [SHR/NDmcr-cp (cp/cp); CP]. We divided 5-week-old CP rats into non-exercise (CP) and exercise (CP-Ex) groups. Wistar-Kyoto rats (WKY) were used as the control group. CP-Ex rats were permitted voluntary exercise on running wheels for 10 weeks. Triglyceride levels were higher and adiponectin levels lower in the CP and CP-Ex groups than in the WKY group. However, triglyceride levels were lower and adiponectin levels higher in the CP-Ex group than in the CP group. The soleus muscles in CP-Ex rats contained only high-oxidative type I fibers, whereas those in WKY and CP rats contained type I, IIA, and IIC fibers. Muscle succinate dehydrogenase (SDH) activity was higher in the CP-Ex group than in the CP group; there was no difference in SDH activity between the WKY and CP-Ex groups. Muscle proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA levels were higher in the CP-Ex group than in the CP group; there was no difference in PGC-1α mRNA levels between the WKY and CP-Ex groups. In CP-Ex rats, longer running distance was associated with increased muscle SDH activity and PGC-1α mRNA levels. We concluded that running exercise restored decreased muscle oxidative capacity and PGC-1α mRNA levels and improved hypertriglyceridemia in rats with metabolic syndrome.     

Heat exposure does not alter eccentric exercise-induced increases in mitochondrial calcium and respiratory dysfunction

Eccentric exercise can lead to muscle damage including dramatic changes to mitochondrial calcium content (MCC) and impaired respiratory function. Heat acclimation can create a cross-tolerance to a number of stresses including eccentric exercise but little is known about any protection to mitochondria. We hypothesised that intermittent heat exposure will lead to improved control of MCC and to preserved mitochondrial function following eccentric exercise. Sprague–Dawley rats were exposed to 3 weeks of intermittent heat exposure (36°C, 40% relative humidity, 6 h/day, 5 days a week) or kept in cool conditions (20°C). Animals were then assigned to a control or exercise group (−14°C decline treadmill exercise for 90 min). MCC, mitochondrial respiration and mitochondrial permeability transition pore opening (mPTP) were measured in mitochondria isolated from the red quadriceps in animals killed immediately, 2 h and 48 h post-exercise. Results showed that heat exposure was associated with lower plasma creatine kinase levels (p < 0.05) post-exercise suggesting lower levels of muscle damage. There was a significant (~500%) rise in MCC (p < 0.001) and a reduction in mitochondrial respiratory control ratio (p < 0.001) 48 h post-exercise. mPTP displayed increased (p < 0.05) sensitivity to calcium immediately and 48 h post-exercise. Thus, decline running led to significant impairment of mitochondria respiration and calcium loading which was more pronounced 48 h post-exercise compared with earlier time points. MCC levels and mitochondrial function were not altered by heat exposure. In conclusion, intermittent heat exposure does not appear to provide protection against mitochondrial dysfunction resulting from eccentric exercise.     

Effects of whole-body heat acclimation on cell injury and cytokine responses in peripheral blood mononuclear cells

To test the hypothesis that whole-body heat acclimation (HA) would increase peripheral blood mononuclear cells’ (PBMC) tolerance to heat shock (HS) and/or alter the release of cytokines (IL-1β, IL-6, IL-10 and TNF-α) to bacterial lipopolysaccharide (LPS), we heat acclimated nine subjects by exercising them for 100 min in a hot environment for 10 days. The subjects’ PBMC were separated and cultured on days 1 and 10 of HA pre- and post-exercise. Pre-exercise PBMC were allocated to three treatments: control (PRE, 37°C), HS (42.5°C for 2 h), or LPS (1 ng mL⁻¹ for 24 h). Post-exercise samples were incubated at 37°C. PBMC lactate dehydrogenase release increased (p < 0.05) after HS but it was not different (p > 0.05) between days 1 and 10 (0.100 ± 0.012 and 0.102 ± 0.16 abs., respectively). LPS treatment induced an increased (p < 0.05) release of cytokines but HA did not alter this response (p > 0.05). Pre-exercise intracellular heat shock protein 72 (Hsp72) was higher (p < 0.05) on day 10 compared to day 1 of HA (13 ± 5 and 8 ± 5 ng mL⁻¹, respectively). HS treatment caused a greater increase (p < 0.05) in Hsp72 than the exercise sessions on HA days 1 and 10. In addition, after HA, the Hsp72 response to HS was reduced (day 1, 129 ± 46; day 10, 80 ± 32 ng mL⁻¹, p < 0.05). In conclusion, HA increases PBMC Hsp72 but it does not reduce cellular damage to HS or alter cytokine response to LPS. We speculate that the stress applied during HA is not sufficient to modify the PBMC response.     

The effects of carbohydrate ingestion during endurance running on post-exercise inflammation and hepcidin levels

The effect of carbohydrate (CHO) consumption during prolonged endurance running on post-exercise inflammation and hepcidin levels was investigated. Eleven well-trained male endurance athletes completed a graded exercise test, followed by two experimental running trials in a randomized order. The two experimental trials consisted of a 90 min run at 75% of the peak oxygen uptake velocity (vVO_2peak), while consuming a solution with either 6% CHO or a placebo (PLA) equivalent at 3 ml kg⁻¹ every 20 min. Serum interleukin-6 (IL-6), free hemoglobin (Hb), haptoglobin (Hp), hepcidin and iron parameters were assessed throughout the post-run recovery period. Serum iron and IL-6 were significantly elevated immediately post-run in both CHO and PLA (p ≤ 0.05), with no differences between trials. Serum-free Hb increased and Hp decreased significantly immediately post-run in both conditions (p ≤ 0.05). Serum soluble transferrin receptor levels were significantly below the baseline at 3 and 24 h post-run in both conditions (p ≤ 0.05). Serum hepcidin concentration recorded 3 h post-run in both conditions was significantly elevated (p ≤ 0.05), and had returned to the baseline by 24 h post-run (p ≤ 0.05). The use of a 6% CHO solution at 3 ml kg⁻¹ 20 min⁻¹ during endurance running did not attenuate the inflammatory response and subsequent increase in serum hepcidin levels during the post-run recovery period.     

Intra-arterial <Emphasis Type="Italic">tert</Emphasis>-Butyl-Hydroperoxide Infusion Induces an Exacerbated Sensory Response in the Rat Hind Limb and is Associated with an Impaired Tissue Oxygen Uptake

The objective of this study was to investigate oxidative stress and oxygen extraction mechanisms in an animal model of continuous intra-arterial infusion of a free radical donor and in an in vitro model using isolated mitochondria. tert-Butyl-hydroperoxide (tert-BuOOH, 25 mM) was infused for 24 h in the left hind limb of rats to induce soft tissue damage (n = 8). After 7 days, we assessed local sensory response, tissue oxygen consumption, oxygen radicals, and antioxidant levels. In vitro mitochondrial function was measured after stimulation of isolated mitochondria of skeletal muscle cells with increasing doses of tert-BuOOH. tert-BuOOH infusion resulted in an increased skin temperature (p = 0.04), impaired function, and a significantly increased pain sensation (p = 0.03). Venous oxygen saturation levels (p = 0.01) and the antioxidant ceruloplasmin (p = 0.04) were increased. tert-BuOOH inhibited mitochondrial function in vitro. Induction of free radical formation in the rat hind limb results in an exacerbated sensory response and is associated with impaired oxygen extraction, which likely results from mitochondrial dysfunction caused by free radicals.     

Temporal association of elevations in serum cardiac troponin T and myocardial oxidative stress after prolonged exercise in rats

The objective of this study was to determine if prolonged exercise resulted in the appearance of cardiac troponin T (cTnT) in serum and whether this was associated with elevated levels of myocardial oxidative stress. Forty-five male Sprague–Dawley rats were randomized into four groups and killed before (PRE-EX), immediately (0HR), 2 (2HR) and 24 h (24HR) after a 3-h bout of swimming with 5% body weight attached to their tail. In all animals serum cTnT was assayed using 3rd generation electrochemiluminescence. In homogenized heart tissue myocardial malondialdehyde (MDA), a marker of lipid peroxidation, glutathione (GSH), and a non-enzymatic estimate of total antioxidant capacity (T-AOC) were assessed spectrophotometrically. At PRE-EX cTnT was undetectable in all animals. At 0HR (median, range: 0.055, 0.020–0.100) and 2HR post-exercise (0.036, 0.016–2.110) cTnT was detectable in all animals (P < 0.05). At 24HR post-exercise cTnT was undetectable in all animals. An elevation in MDA was observed 0HR (mean ± SD: 1.7 ± 0.2 nmol mgpro⁻¹) and 2HR (1.6 ± 0.3 nmol mgpro⁻¹) post-exercise compared with PRE-EX (1.3 ± 0.2 nmol mgpro⁻¹; P < 0.05). The antioxidant response to this challenge was a significant (P < 0.05) decrease in GSH 2HR and 24HR post-exercise. Despite this T-AOC did not alter across the trial (P > 0.05). The results indicated that prolonged and strenuous exercise in rats resulted in an elevation in cTnT, a biomarker of cardiomyocyte damage, in all animals 0HR and 2HR after exercise completion. The time course of cTnT elevation was temporally associated with evidence of increased lipid peroxidation in the rat heart.     

Spleen morphology and hematological changes in rats following withdrawal of Nigerian Qua Iboe Brent crude oil

Possible amelioration of splenic damage and hematological changes in Nigerian Qua Iboe Brent crude oil-exposed rats following its withdrawal was investigated. A total of 56 male albino rats weighing between 200–250 g were used for this study. The rats received oral administration of 165 mg/kg body weight (low-dose), 330 mg/kg body weight (medium-dose) and 660 mg/kg body weight (high-dose) of Nigerian Quo Iboe Brent crude oil every 48 h for 28 days. Later, the crude oil was withdrawn from some rats for a period of 8 weeks. Hematological parameters and spleen morphology of rats that received crude oil and the rats from which the crude oil was withdrawn were compared with the controls that did not receive crude oil treatment. Administration of Nigerian Qua Iboe Brent crude oil significantly (p < 0.05) reduced the PCV levels in low-dose, low-dose crude oil-withdrawn, medium-dose crude oil-withdrawn, high-dose, and high-dose crude oil-withdrawn groups of rats. The EC was also reduced significantly (p < 0.05) in the medium- and high-dose groups of rats. In the same manner, TWBC was significantly (p < 0.05) reduced in the medium-dose crude oil-withdrawn, high-dose, and high-dose crude oil-withdrawn rats. It was only at low-dose level, after 8 weeks of crude oil withdrawal that there was a reduction in splenic weight. Splenic section (histopathology) of rats exposed to different doses of crude oil over 28-day period showed reticuloendothelial hyperpasia of the red pulp and variable degree of haemosiderin deposits. These changes were not completely ameliorated after 8 weeks of crude oil withdrawal. This study has shown that withdrawal of Nigerian Qua Iboe Brent crude oil from exposed rats did not reverse the splenic damage and the haematologic changes associated with this environmental pollutant.     

Cardiac mechanisms underlying normal exercise tolerance: gender impact

The aim of this study is to test our hypothesis that normal exercise tolerance differs according to gender and to identify potential functional cardiac relationships, which could explain those differences. A total of 44 healthy individuals with mean age of 49 ± 12 years (28–74 years, 22 males) constituted the study cohort. All individuals underwent resting and exercise Doppler echocardiogram simultaneously with peak oxygen uptake analysis (pVO₂). At equal pVO₂, males achieved higher peak exercise workload (p < 0.001) and females higher heart rate (p < 0.001) but the two groups maintained similar indexed left ventricular (LV) stroke volume (SV) and cardiac output. Indexed LV end-diastolic (LVDVI) and end-systolic volumes (LVSVI) were smaller in females (p < 0.001 and p < 0.01, respectively), but filling time (FT) was shorter (p < 0.001) and they had higher early diastolic (E) velocity (p = 0.004), E/E _m (myocardial E velocity) (p < 0.001) and global longitudinal strain rate atrial velocity (GLSRa′) (p = 0.02), compared to males. In males, workload (p < 0.01), LVDVI (p < 0.01), LVSVI (p < 0.05), SVI (p < 0.001) directly but LV myocardial isovolumic relaxation time (IVRTm) (p < 0.01) inversely correlated with pVO₂. In females, mitral E velocity (p < 0.01), GLSRs′ (p < 0.05) positively and LVFT negatively (p < 0.05) correlated with pVO₂. In a multivariable analysis SVI in males (p < 0.01) and GLSRs′ in females (p < 0.01) were the strongest predictors for pVO₂. Thus, normal exercise capacity as determined by pVO₂ is related to the indexed stroke volume in males and left atrial pressure in females. These native normal differences between genders may explain the known vulnerability of women to endurance exercise compared to men.     

Acute and chronic toxicity studies of Erythrina senegalensis DC stem bark extract in mice

The toxicity of chloroform stem bark extract of Erythrina senegalensis DC, a medicinal plant with anti-inflammatory activity, was studied in vivo and in vitro. The LD₅₀ i.p. of the extract was 526 mg/kg after an acute toxicity test (24 h). A brine shrimp lethality test with the extract gave LC₅₀ of 60.86 ppm. The chronic studies revealed alterations in the levels of biochemical markers of hepatic and cardiac damage. The alterations were, however, not significant except in the group fed the highest inclusion of the extract (1.0 g extract/kg feed) where significant (p < 0.05) increases in the activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were observed. Hematological assessments of mice in this group showed significant (p < 0.05) decreases in the red blood cell count and the packed cell volume. Increases in the relative weights of the liver and heart were also significant (p < 0.05). Lipid peroxidation product levels assayed as malondialdehyde was significantly (p < 0.05) elevated in the groups fed 0.5 and 1.0 g/kg of feed at day 84. Significant histopathological changes like myocardial hemorrhages and degeneration of hepatocytes were observed in the heart and liver respectively.     

The influence of physical exercise on the generation of TGF-β1, PDGF-AA,and VEGF-A in adipose tissue

Adipose tissue is an important organ that produces and secretes hormones and cytokines, including TGF-β1, PDGF-AA, and VEGF-A. The goal of the present study was to investigate the influence of a single session of acute exercise, as well as the prolonged endurance training on the production of TGF-β1, PDGF-AA, and VEGF-A in the subcutaneous white adipose tissue in rats. Rats were randomly divided into two groups: untrained (UT, n = 30) and trained rats (T, subjected to 6-week endurance training with increasing load, n = 29). Both groups were subjected to an acute exercise session with the same work load. The rats were killed before (UTpre, Tpre), immediately after (UT0h, T0h), or 3 h (UT3h, T3h) after exercise and adipose tissue samples collected. Growth factor mRNA was evaluated using RT-PCR; the protein levels were measured before and after training (UTpre and Tpre) using the immunoenzymatic method. TGF-β1 and PDGF-AA mRNA levels were decreased in the UT3h rats compared to the UTpre rats (P = 0.0001 and P = 0.03, respectively), but the VEGF-A mRNA level remained unchanged in the UT0h and UT3h rats compared to UTpre rats. TGF-β1, PDGF-AA and VEGF-A mRNA levels were decreased in the T3h rats compared to Tpre (P = 0.0002, P = 0.02, and P = 0.03, respectively). TGF-β1, PDGF-AA and VEGF-A mRNA levels significantly increased in the Tpre rats compared to UTpre (all P = 0.0002). However, the protein levels remained constant. In conclusion, prolonged physical exercise increases growth factor mRNA in adipose tissue but not protein levels.