Effect of chronic airway inflammation and exercise on pulmonary and systemic antioxidant status of healthy and heaves-affected horses

In heaves-affected horses the relation between oxidant status, airway inflammation (AI) and pulmonary function (PF) is unknown. The oxidant status of blood and pulmonary epithelial lining fluid (PELF) of healthy (H, n = 6) and heaves-affected horses in clinical remission (REM, n = 6) and in crisis (CR, n = 7) was assessed at rest, during and after standardised exercise test by measurement of reduced and oxidised glutathione, glutathione redox ratio [GRR%]; uric acid and 8-epi-PGF2alpha. Oxidant status was related to PF parameters (mechanics of breathing and arterial blood gas tension) and Al parameters (bronchoalveolar lavage [BAL] neutrophil % and AI score). Haemolysate glutathione was significantly different between groups and was correlated with PF and AI parameters; GRR in PELF was increased during CR and was correlated with PF and AI parameters. Exercise induced an increase of plasma uric acid that was significantly higher both in REM and CR. PELF 8-epi-PGF2alpha was significantly increased in CR and correlated with PF and AI parameters. These results suggest that oxidative stress occurring in heaves is correlated with PF and AI and may be locally assessed by PELF glutathione status, uric acid and 8-epi-PGF2alpha. Systemic repercussions are reflected by assay of GSH in resting horses and by uric acid in exercising horses.     

Effect of hyonate administration on pulmonary function and indices of oxidative stress in COPD horses in clinical remission at rest and after exercise

Pulmonary function tests, bronchoalveolar lavages, and venous blood samplings were performed 24 hours before and one hour after a standardized strenous treadmill exercise test on six horses suffering from chronic obstructive pulmonary disease (COPD) in clinical remission. Pulmonary function test consisted of the measurement of the mechanics of breathing and arterial blood gases analyses. During the exercise tests, heart and respiratory rates, and venous plasma lactate, pH and packed cell volume were controlled. Venous blood was analyzed for some markers of the oxidative stress, i.e., hemolysate glutathione redox ratio and oxidized glutathione, and plasma uric acid. BAL was analyzed for cell cytology as well as for markers of oxidative stress, i.e., glutathione redox ratio, and isoprostanes concentration. The procedure was repeated twice, i.e., before and after two IV injections of 40mg hyaluronate administered at seven day intervals. The results were compared to assess a possible influence of the treatment on the pulmonary and systemic inflammatory and/or oxidative status of these horses.Hyaluronate did not influence the pulmonary function test or the physiological parameters recorded during exercise. There was a decrease in the percentage of BAL neutrophils after the treatment, suggesting a possible anti-inflammatory effect at the pulmonary level. As well, the concentration of isoprostanes in the pulmonary epithelium lining fluid was significantly lower after the treatment, which might be either a consequence of the decrease of the BAL neutrophils, or related to a possible antioxidant effect of the treatment. Lastly, the exercise-induced increase in plasma uric acid was significantly less marked after the treatment, which could be due to a systemic antioxidant effect of the hyaluronate.In conclusion, this preliminary study brings some evidence that hyaluronate could have some antiinflammatory and antioxidant effects at the pulmonary—and systemic—level in COPD horses in remission. However, it does not help to understand the possible mechanisms underlying these observations. Further studies are now necessary to better understand its action, to assess the effect of the product on the pulmonary function of horses suffering from other respiratory problems as well as to assess the efficiency of other ways of administration, i.e., nebulization.     

Comparison of the antioxidant status in tracheal and bronchoalveolar epithelial lining fluids in recurrent airway obstruction

REASONS FOR PERFORMING STUDY: Following a period of airway inflammation the clearance of inflammatory cells along the mucociliary escalator may impose a considerable oxidant load on the trachea. OBJECTIVES: To determine the degree of oxidative stress in tracheal epithelial lining fluid (ELF) in comparison to that present in peripheral airways after an acute exposure to organic dust. METHODS: Tracheal wash fluid and bronchoalveolar lavage fluid (BALF) were collected for cytology and antioxidant analyses from 6 recurrent airway obstruction (RAO)-affected horses and 6 healthy control horses before and after stabling on straw bedding for 24 h. RESULTS: In RAO-affected horses, organic dust exposure resulted in a significant decrease in ascorbic acid concentration in tracheal ELF (P<0.0001), which was greater than the decrease in bronchoalveolar ELF (P = 0.0003). The percentage decrease in tracheal ELF ascorbic acid correlated with the percentage decrease in bronchoalveolar ELF ascorbic acid (r = 0.76; P = 0.004) following exposure. CONCLUSIONS: Acute organic dust exposure results in significant antioxidant depletion in the trachea, which may reflect inflammation and oxidative processes in peripheral airways. POTENTIAL RELEVANCE: Further work is required to evaluate the role of ascorbic acid depletion in the pathogenesis of RAO.     

Effects of exercise and oral antioxidant supplementation enriched in (n-3) fatty acids on blood oxidant markers and erythrocyte membrane fluidity in horses

The aim of this study was to investigate in a placebo-controlled field study the effect of a (n-3)-vitamin supplementation on erythrocyte membrane fluidity (EMF), oxidant/antioxidant markers and plasmatic omega3/omega6 fatty acid ratio (FAR) in 12 eventing horses. Venous blood was sampled at rest before (PRE) and after (POST) a three week treatment period with either the supplement (group S, n=6) or a placebo (group P, n=6) as well as after 15min (POST E15') and 24h (POST E24h) after a standardised exercise test. The following markers were analysed: EMF, plasma antioxidant capacity of water and lipid soluble components, ascorbic acid, uric acid (UA), glutathione (reduced: GSH, oxidised: GSSG), vitamin E (Vit E), beta-carotene, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity, selenium, copper (Cu), zinc (Zn), oxidised proteins (Protox), lipid peroxides (Pool) and FAR. EMF did not differ between group S and P after treatment, but GPx remained unchanged in group S whereas it decreased in group P and plasma Cu/Zn ratio remained unchanged whereas it increased in group P. FAR were significantly increased in group S. Exercise induced a significant decrease of EMF (POST vs. E24h) in both groups, but which was significantly lower at E15' in group S than in group P. Exercise induced a significant increase of UA and ACW (POST vs. E15') and Protox (POST vs. E24h) in both groups. An exercise-related decrease in GSH and Pool (POST vs. E15') was found in group P, whereas Vit E and FAR (POST vs. E24h) significantly decreased in both groups. The study showed that exercise induced a decrease in EMF in horses associated with changes of blood oxidative balance. The (omega-3)-vitamin supplementation tested improved the oxidative balance poorly but delayed the exercise-induced decrease of EMF and increased the FAR.     

Exercising Blood Gas Analysis, Dynamic Upper Respiratory Tract Obstruction, and Postexercising Bronchoalveolar Lavage Cytology—A Comparative Study in Poor Performing Horses

Respiratory abnormalities are common causes of decreased performance in horses presumably because of impaired pulmonary gas exchange. The objectives of the present study were to describe respiratory abnormalities in poorly performing horses and to investigate the relationships between dynamic upper respiratory tract (URT) videoendoscopy, postexercising bronchoalveolar lavage (BAL) cytology, and exercising arterial blood gas analysis. Medical records of 93 horses with exercise intolerance, which presented for treadmill evaluation, were reviewed. Relationships between horse demographics, treadmill endoscopic findings, exercising blood gas values, and BAL cytology results were examined. A total of 25 (27%) horses had a URT obstruction and 91 (98%) horses had abnormal BAL cytology; 73 (78%) had evidence of inflammatory airway disease (IAD) and 83 (89%) had exercise-induced pulmonary hemorrhage (EIPH). In all, 39 (42%) horses had abnormal blood gas values. Dynamic URT obstruction was significantly associated with exercising hypoxemia (P = .036). There were no significant relationships between gas exchange and IAD or between EIPH. Out of 24 (26%) horses with combined URT obstruction and abnormal BAL, horses with URT obstruction and EIPH were more likely to be hypoxic during exercise (P = .037). It was concluded that horses with dynamic URT abnormalities are likely to have exercising hypoxemia. Although IAD and EIPH were commonly indentified in poor performers, they were not significantly associated with abnormal exercising blood gas analysis.     

Effect of oral antioxidant supplementation on blood antioxidant status in trained thoroughbred horses

The oxidant/antioxidant equilibrium of trained thoroughbred horses (n = 40) was assessed on three occasions during a period of three months under field conditions by blood antioxidant markers analysis, i.e. plasma ascorbic acid (AA), plasma antioxidant capacity of water-soluble components (ACW), whole blood (GSH) and oxidised (GSSG) glutathione, plasma alpha-tocopherol and beta-carotene, plasma antioxidant capacity of lipid-soluble components (ACL), red blood cell superoxide dismutase (SOD) and glutathione-peroxidase activity (GPx) and plasma trace-elements, i.e. selenium (Se), copper (Cu), zinc (Zn). A control group of ten horses receiving a placebo and an antioxidant group of 30 horses orally supplemented with an antioxidant mixture were randomly formed. An antioxidant imbalance was observed after three months in the control group, reflected by a significant decrease in GSH, SOD, GPx, Se (P < 0.05) and a significant increase in GSSG (P < 0.05). The antioxidant supplement prevented GPx and Se decrease and significantly increased ACW, alpha-tocopherol, beta-carotene and ACL (P < 0.05). Significant sex- or age-related differences were found for AA, ACW, alpha-tocopherol, SOD, GPx and Se, and there were significant correlations between ACW-AA, ACL-alpha-tocopherol, GPx-Se, CPK-Se, CPK-alpha-tocopherol and CPK-Cu. This field study has shown that trained thoroughbred horses undergo significant changes of several blood antioxidant markers and that oral antioxidant supplementation might partially counterbalance these changes by improving the hydrophilic, lipophilic and enzymatic antioxidant blood capacity.     

Evaluation of a risk-screening questionnaire to detect equine lung inflammation: results of a large field study

Reasons for performing study: The diagnosis of equine recurrent airway obstruction (RAO) and inflammatory airway disease (IAD) is based on clinical signs and increased inflammatory cell percentages in the bronchoalveolar lavage (BAL) fluid. Since a BAL is an invasive procedure, a risk‐screening questionnaire (RSQ) would be a valuable screening tool for lung inflammation. Objective: To evaluate the accuracy of a RSQ to detect lower airway inflammation (LAI) in a large population of horses. Methods: A standardised BAL was performed in the field on 167 horses in Alberta, Canada. Horses were separated into 3 categories: 1) BAL normal; 2) BAL mild to moderate LAI (MLAI), and 3) BAL severe LAI (SLAI). The horse owners were asked to complete a RSQ. The RSQ scores were compared to the BAL results to determine the likelihood of a horse having MLAI, SLAI or no LAI. Results: Based on BAL cytology, 28 (17%) horses were normal and 139 (83%) were abnormal, with 110 (66%) showing MLAI and 29 (17%) SLAI. Horses with SLAI and MLAI had a mean RSQ score of 0.95 and 0.70, respectively, compared to 0.60 for normal BAL horses. Horses with SLAI showed more clinical signs than normal and MLAI horses. The sensitivity and negative predictive values of the RSQ for detecting SLAI using a cut‐off score of 0.87, were excellent at 0.90 (95%CI 0.73–0.98) and 0.96 (95%CI 0.82–1.00). Questions on the clinical signs typically found in RAO cases differed significantly between horses with BAL SLAI and those with BAL normal. Conclusions: Prevalence of MLAI was high in this population. Although the RSQ did not allow differentiating normal horses from horses with MLAI, it has a high sensitivity to detect horses with SLAI and is therefore a good screening tool for SLAI.     

Bronchoconstrictive properties of inhaled 8-epi-PGF2alpha in healthy and heaves-susceptible horses

The 8-epi-PGF2alpha is a marker of oxidative stress which is increased in lungs of asthmatic humans and heaves-susceptible horses. 8-Epi-PGF2alpha has also been demonstrated to be an in vitro and in vivo bronchoconstrictor in humans and rodents. We hypothesised that inhaled 8-epi-PGF2alpha was a bronchoconstrictor in healthy and heaves-susceptible horses in clinical remission. The effect on ventilatory mechanics of nebulised 8-epi-PGF2alpha was compared to that of PGF2alpha and U46619, a thromboxane A2 agonist. Pulmonary resistance (R(L)) and dynamic compliance (Cdyn) were assessed in six healthy horses and in six heaves-susceptible horses in clinical remission before (baseline) and immediately after a single inhalation challenge of 1 mg 8-epi-PGF2alpha PGF2alpha, or U46619 and placebo. R(L) and Cdyn were unchanged after inhalation of 8-epi-PGF2alpha in healthy horses. In heaves-susceptible horses, 8-epi-PGF2alpha induced a significant increase of R(L) and a significant decrease of Cdyn when compared to baseline values. Differences between R(L) and Cdyn values after 8-epi-PGF2alpha inhalation and those of placebo inhalation were not significant. Differences with healthy horses were not significant. PGF2alpha and U46619 induced a significant bronchoconstriction in healthy (R(L) and Cdyn versus baseline) and heaves-susceptible horses (R(L) and Cdyn, versus baseline and placebo), the R(L) increase in heaves-susceptible horses after PGF2alpha inhalation was significantly higher than that in healthy horses. Our results suggest that 8-epi-PGF2alpha is not a bronchoconstrictor in healthy horses, and a bronchoconstrictor far less efficient than PGF2alpha and U46619 at the same dose in heaves-susceptible horses.     

Lack of clinical efficacy of a phosphodiesterase-4 inhibitor for treatment of heaves in horses

Phosphodiesterase-4 (PDE 4) enzyme inhibitors have been shown to have anti-inflammatory properties in various animal disease processes and therefore could be effective drugs for the treatment of equine airway diseases. The purpose of this study was to evaluate the efficacy and adverse effects of the PDE 4 inhibitor L-826,141 in horses with heaves. In a blinded parallel design, horses with heaves exposed daily to moldy hay were given a placebo for 14 days and then administered either L-826,141 (n = 6; loading dose of 1 mg/kg IV followed by 0.5 mg/kg IV q48h) or dexamethasone (n = 6; 0.04 mg/kg IV q24h) from days 15 to 29 (study 1). Pulmonary function and bronchoalveolar (BAL) cytology were evaluated weekly from baseline (day 0) to 29 days. In study 2, horses were treated with L-826,141 (1.0 mg/kg IV q24h) for 8 days. Although ex vivo lipopolysaccharide-induced tumor necrosis factor (TNF)-alpha and LTB4 production by fresh blood were inhibited up to 90% after repeated administrations of L-826,141, this treatment failed to improve lung function. In contrast, dexamethasone (positive control) treatment resulted in significant improvement in lung mechanics and airway function in all horses. Neither drug had a significant effect on BAL total cell counts and differential cytology. Administration of the PDE 4 inhibitor L-826,141 for up to 14 days to horses with heaves was not associated with an improvement in airway function or inflammation. These findings suggest that the PDE 4 enzyme is not a key mediator of lung inflammation in heaves.     

The Effect of Exercise and Nutritional Supplementation on Proinflammatory Cytokine Expression in Young Racehorses During Training

The inflammatory response to vigorous exercise ranges from the mild symptoms of delayed-onset muscle soreness to debilitating injuries affecting soft tissue, joint, and bone. Although there is a great deal of information available on the inflammatory response to exercise in human athletes, less information is available regarding the inflammatory response to exercise in young horses undergoing training for racing careers. Here, we assessed the cytokine response to exercise in a group of young Thoroughbred racehorses during their initial training. Because there is interest in nonpharmacologic approaches to control or ameliorate exercise-induced inflammation, we also examined the anti-inflammatory effect of a nutritional supplement fed to half of the horses undergoing training. Twenty-five Thoroughbred horses aged 2 years were followed through their initial race training. Peripheral blood samples were collected at various times during the exercise for the quantitation of lactic acid, oxidative stress, and inflammatory cytokine gene expression. There was an intensity-dependent effect of exercise on lactate, malondialdehyde, and proinflammatory cytokine gene expression. Although training itself was associated with an overall reduction in inflammatory markers, horses receiving the supplement exhibited further reductions in their indicators of inflammation. As such, this study provides novel evidence of nutritional supplementation reducing postexercise inflammation.     

Increased adenosine concentration in bronchoalveolar lavage fluid of horses with lower airway inflammation

Several reports have suggested a role for adenosine in the pathogenesis of chronic airway conditions and this has led to new therapeutic strategies to limit airway inflammation. In this study, detectable levels of adenosine in bronchoalveolar lavage (BAL) samples from 11 horses with non-infectious lower-airway inflammation and 14 healthy controls are reported, with significantly higher values in horses with airway inflammation. Although these increased levels did not correlate with changes in neutrophil percentage in BAL, a positive association between adenosine levels and signs of lower airway inflammation (clinical score) was observed. These novel findings support the hypothesis that adenosine may contribute to bronchoconstriction and also act as a pro-inflammatory mediator in the bronchoalveolar milieu of horses with airway inflammation. Further investigation of this axis could lead to new approaches for the treatment of highly prevalent lower airway inflammatory conditions in the horse.     

Biochemical and antioxidant changes in plasma and erythrocytes of pentathlon horses before and after exercise

Abstract: Physical exercise in the horse induces a series of normal physiological and biochemical adaptations. Increasing metabolism and oxygen uptake may induce oxidative stress in various organs. The aim of this study was to examine exercise-induced changes in some plasma and RBC biochemical and antioxidant variables in pentathlon horses. Blood samples were taken from 14 horses before, immediately after, and 24 hours after competing in two 1-minute runs of intense exercise over jumps. The peak intensity periods were preceded by a 20-minute warm-up and separated by a 20-minute break. The following plasma biochemical analytes were determined: total protein, uric acid, and lactate concentrations, and lactate dehydrogenase (LDH) and creatine kinase (CK) activities. Total antioxidant status (TAS) and the ferric reducing ability of plasma (FRAP) also were measured. Thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), and total protein concentrations, and glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) activities were determined in RBC hemolysates. Significantly increased concentrations of total protein, lactate, and FRAP, and increased activities of CK and LDH were observed immediately postexercise compared with pre-exercise samples (P < .05). All results returned to approximately initial values after 24 hours of rest. RBC GSH and TBARS concentrations did not change immediately after exercise, but decreased after 24 hours of rest (P < .05). Plasma uric acid and FRAP values were positively correlated in a linear model ( r = .78). In summary, the type of exercise applied in this study, which can be considered quite usual for pentathlon horses, caused detectable biochemical and lipid peroxidative changes in plasma and RBCs. FRAP and TAS values changed in opposite directions, indicating that when antioxidant capacity is assessed using different methods, highly different results may be obtained.     

Effects of a Novel Dietary Supplement on Indices of Muscle Injury and Articular GAG Release in Horses

This study determined the ability of an oral nutraceutical supplement to attenuate the oxidative stress and inflammation that occurs in muscles and joints with repeated bouts of high-intensity exercise in horses. The supplement, fed daily, was comprised of whole dried mushrooms, golden flaxseed, omega-3 fatty acids, plant-based enzymes, a melon-concentrate powder, and Saccharomyces cerevisiae boulardii. Ten horses participated in a partial cross-over design, with 7 horses completing the Control trial and 7 horses completing the supplement trial. Blood and synovial fluid samples (from the intercarpal joint) were taken before, and at 1 and 24 hours after a standardized, repeated high-intensity exercise test that was performed before supplementation and on the 22nd day of supplementation. At the end of the supplement trial exercise resulted in reduced concentrations of plasma markers of oxidative stress (decreased thiobarbituric acid reactive substances, with increased total antioxidant status and increased superoxide dismutase activity); there was no effect on plasma markers of muscle injury (creatine, creatine kinase, and aspartate aminotransferase) or inflammation (PGE₂, nitric oxide). Within synovial fluid, there was a tendency for increased superoxide dismutase activity, and decreased concentration of glycosaminoglycans. It is concluded that the supplement, when fed to horses as part of the normal diet for 23 days, was associated with reduced concentrations of markers of oxidative stress and inflammation in muscle and synovial fluid.     

Serum concentration of surfactant protein D in horses with lower airway inflammation

Reasons for performing study: Surfactant protein D (SP‐D), mainly synthesised by alveolar type II cells and nonciliated bronchiolar cells, is one important component of innate pulmonary immunity. In man, circulating concentrations of SP‐D are routinely used as biomarkers for pulmonary injury. To date, serum SP‐D levels have only been investigated in horses in an experimental model of bacterial airway infection. Objectives: To compare serum SP‐D concentrations at rest and after exercise in horses with and without inflammatory airway disease (IAD). Methods: Venous blood samples were collected from 42 Standardbred racehorses at rest and 60 min after performing a standardised treadmill exercise test. Tracheal wash and bronchoalveolar lavage fluid (BALF) samples were collected after exercise. Based on BALF cytology, 22 horses were defined as IAD‐affected and 20 classified as controls. Serum SP‐D concentrations were assessed using a commercially available ELISA kit and statistically compared between groups of horses and sampling times. Results: Serum concentrations of SP‐D in IAD‐affected horses were significantly higher than those of control horses, both at rest and after exercise. Within the IAD‐affected group, no significant correlation was found between serum SP‐D concentrations and BALF cytology. Within each group of horses (IAD and control), no significant influence of exercise was found on serum SP‐D levels. Conclusions: This is the first study determining serum SP‐D concentrations in a noninfectious, naturally occurring form of lower airway inflammation in horses. The results highlight that IAD is associated with a detectable, though moderate, increase of circulating SP‐D levels. Potential relevance: Serum concentration of surfactant protein D could represent a potentially valuable and readily accessible blood biomarker of equine lower airway inflammation.     

The oxidant/antioxidant equilibrium in horses

Since "free radical research" started in 1954, understanding the role of oxidants and antioxidants in physiological and pathological conditions has increased continuously. Oxidants are essentially generated by metabolic enzymes, inflammatory cells and mitochondrial electron leakage; they are indispensable for the cellular redox regulation and may, under certain conditions, have a pro-inflammatory stimulatory role. Endogenous and exogenous antioxidants counterbalance the oxidative processes and so maintain the oxidant/antioxidant equilibrium. Excessive oxidant generation or antioxidant insufficiency can lead to oxidative stress. The aims of this review are: (1) to provide an insight into the concept of the oxidant/antioxidant equilibrium by briefly introducing the oxidant and the antioxidant systems; (2) to describe how the oxidant/antioxidant equilibrium or oxidative stress can be evaluated in horses, and (3) to summarise current knowledge about oxidative stress in equine medicine and equine exercise physiology.     

Bronchoaveolar lavage for the diagnosis of lower airway disorders in horses

Equine pulmonary disease and especially the terminology of lower airway disease have been subject to discussion. Besides established terms such as 'Chronic Obstructive Pulmonary Disease' (COPD) and Chronic bronchitis, the term 'small airway disease' (SAD) has been introduced, for respiratory disease with inflammation in the lower airways in combination with exercise intolerance. Bronchoalveolar lavage (BAL) enables the practitioner to diagnose SAD in an early stage when there are no other signs such as coughing or exudate in the trachea. The BAL fluid is microscopically examined after centrifugation. BAL cytology, especially neutrophilia, eosinophilia, and an increase in mast cells, is important, not only to decide whether SAD is present but also to determine in the choice of therapy.     

Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone

REASONS FOR PERFORMING STUDY: Inhaled ozone can induce oxidative injury and airway inflammation. Horses affected by recurrent airway obstruction (RAO) have a decreased pulmonary antioxidant capacity, which may render them more susceptible to oxidative challenge. It is currently unknown whether RAO-affected horses are more susceptible to oxidative stress than those unaffected by RAO. OBJECTIVES: To determine whether ozone exposure induces greater oxidative stress and airway inflammation in RAO-affected horses in remission than in healthy horses. METHODS: Seven healthy control horses and 7 RAO-affected horses were exposed to 0.8 ppm ozone for 2 h at rest. RESULTS: At baseline, bronchoalveolar lavage fluid (BALF) ascorbic acid concentrations were lower in RAO-affected horses than healthy controls. Ozone appeared to preferentially oxidise glutathione rather than ascorbic acid 6 h after exposure. Individual healthy and RAO-affected horses demonstrated oxidation of BALF glutathione after ozone exposure. Overall, RAO-affected horses did not demonstrate increased oxidative stress following ozone exposure, compared with healthy horses. Ozone did not induce significant airway inflammation in either group. CONCLUSIONS: RAO-affected horses in remission are not more sensitive to ozone despite a decreased pulmonary antioxidant capacity. Sensitivity to ozone appears to be independent of initial pulmonary antioxidant status. POTENTIAL RELEVANCE: Horses with high susceptibility to oxidative stress may benefit from antioxidant supplementation.     

Effects of 8-epi-PGF2α on isolated bronchial smooth muscle of healthy and heaves-affected horses

8-Epi-PGF2alpha, a prostaglandin-like compound generated by oxidative stress, has been shown to be an in vitro bronchoconstrictor in airways from healthy laboratory animals and healthy humans, but it has never been studied in diseased airways. Here, the bronchoconstrictive capacity of 8-epi-PGF2alpha on isolated bronchial rings (BR) of healthy and heaves-affected horses was evaluated by comparing the maximal effect and the potency of 8-epi-PGF2alpha to those of (1) acetylcholine (ACh), (2) its stereoisomer PGF2alpha and (3) its synthetic receptor agonist, U46619. Furthermore, the potential capacity of 8-epi-PGF2alpha to enhance the cholinergic (ACh) responsiveness of bronchial smooth muscle was investigated. 8-Epi-PGF2alpha contracted BR with a rank order of efficacy of Ach > U44619 > PGF2alpha > 8-epi-PGF2alpha in both healthy and heaves-affected horses. The contractile maximal response elicited by 8-epi-PGF2alpha was significantly smaller than that elicited by the other drugs, but was significantly higher in BR from heaves-affected horses than in those sampled in healthy horses, whilst pD2 values were similar. A subthreshold concentration of 8-epi-PGF2alpha (10-7 M) did not induce in vitro cholinergic hyper-responsiveness in BR of either healthy or heaves-affected horses. In conclusion, it has been demonstrated that 8-epi-PGF2alpha is an in vitro bronchoconstrictor of minor importance in healthy horses, but whose efficacy is significantly increased in heaves-affected horses.