Interlobular distribution of hepatic xenobiotic-metabolizing enzyme activities in cattle, goats and sheep

Microsomal and cytosolic enzymes that metabolize xenobiotics were measured in composite samples representing entire livers and in samples from three lobes, using livers of cattle, goats and sheep. Within individual species, concentrations of cytochrome P-450 and b5 and activities of NADPH cytochrome c reductase, aldrin epoxidase, aminopyrine N-demethylase, ethoxycoumarin O-deethylase, microsomal and cytosolic stilbene oxide (epoxide) hydrolase and glutathione S-transferase were not different (P greater than .05) among the various hepatic lobes. Among species, several activities differed (P less than .05), with cattle livers generally having lower values than sheep or goats.     

The development of drug-metabolizing enzymes in female sheep livers

The purpose of this investigation was to determine age-related changes of some hepatic drug-metabolizing activities in Lacaune ewes in the foetal, neonatal (1 and 4 weeks), growing (7 months), pregnant (11 months) and adult (6 years) stages. Although microsomal cytochrome P-450 was not detected in 3-month-old foetuses, it increased regularly from 1-week- to 11-month-old animals. Among mixed-function oxidases, the development of aminopyrine and ethylmorphine N-demethylases, benzo(alpha)pyrene hydroxylase and ethoxycoumarin O-deethylase were correlated to that of total cytochrome P-450. Due to their presence in foetal liver or their more rapid evolution, cytochrome b5, NADPH cytochrome c reductase, aniline hydroxylase, benzphetamine N-demethylase and erythromycin N-demethylase did not parallel the ontogenesis of cytochrome P-450. Hepatic transferases showed different developmental patterns from mono-oxygenases, so UDP glucuronyltransferase was detected in the foetus, reached maximum activity in all young ages up to the pregnant stage and subsequently fell in adult ewes. Concerning glutathione S-transferase accepting 1-chloro-2,4-dinitrobenzene as substrate, similar values were obtained in the foetus and all young animals, whereas five- to tenfold higher values were obtained in both pregnant and adult female sheep. N-acetyltransferase using sulphamethazine did not significantly change from foetuses to adults but there were large differences in the capacity of hepatic acetylation between animals belonging to the same group.     

Characterization of xenobiotic biotransformation in hepatic, renal and gut tissues of cattle and sheep

Microsomal and cytosolic preparations of hepatic, renal, ileal and ruminal tissues of cattle and sheep were used to measure oxidative, hydrolative and conjugative biotransformations of 11 xenobiotic substrates. Within species, enzyme activities were generally higher (P less than .05) in hepatic than non-hepatic tissue but, in both species, non-hepatic tissue exhibited considerable capacities for metabolizing certain substrates. Sheep rumen wall (with papillae) was notably high in cytochrome P-450 content (34% of hepatic value), in glutathione conjugation of ethacrynic acid (223% of hepatic activity; P less than .05), and UDP-glucuronidation of estrone (290% of hepatic activity; P less than .05). Sheep differed (P less than .05) from cattle, having lower cytochrome P-450 content in liver and ileum (but not kidney); lower N-demethylase activity in liver, but two- to threefold higher activity in kidney; lower sulfotransferase activity in liver and kidney; and higher glutathione S-transferase activity toward certain substrates. UDP-glucuronidation varied too widely among substrates to afford strong generalization in comparisons among tissues or between species. Non-hepatic tissues in ruminants exhibit considerable capacities for oxidative, hydrolative and conjugative metabolism of xenobiotics. Sheep and cattle differ widely in hepatic and non-hepatic capacities for biotransforming certain xenobiotics.     

A pilot study on the corneal curvatures and ocular dimensions of horses less than one year of age

Intraocular lenses (IOLs) have been implanted in adult equine eyes after cataract surgery. Foals and weanlings comprise a large proportion of those horses undergoing cataract surgery. Due to potential differences in the size and corneal curvature of the juvenile eye, it is not currently known whether implantation of adult IOLs is appropriate in foals and weanlings. The objective of the study was to measure the anterior chamber depth (ACD), central lens thickness (CLT), vitreous chamber depth (VCD), axial globe length (AGL) and corneal curvature of horses less than one year of age. The axial dimensions from one eye of 10 foals were measured using simultaneous A and B scan ultrasonography. The corneal curvature from one eye of 7 weanlings was determined using a modified photokeratometer. Ultrasonography revealed a mean ACD of 4.94 mm, mean CLT of 9.38 mm, mean VCD of 18.96 mm and mean AGL of 33.32 mm for the foals. The mean corneal curvature was 15.4 diopters (D). The mean ACD, CLT, VCD and AGL of the foals were less than the measurements reported in the literature for adult horses. The mean corneal curvature was similar to the values reported by some authors for adult horses. Due to the differences in axial dimensions between adult and juvenile eyes, an IOL that corrects vision in an adult horse might not adequately correct vision in a horse less than one year of age.     

Differential Expression of IGF1, IGFBP5, MSTN,and MYH1 Across Different Age Classes in American Quarter Horses

The objective of this study was to determine the influence of age on expression of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein (IGFBP5), myostatin (MSTN), and myosin (MYH1) genes which are related to growth and muscle development in the American Quarter Horse. Thus, horses (n = 10) from weanling, yearling, 2-, 3-, and 10-year-old age classes were sampled and gene expression was assessed by RT-qPCR. ΔC_T was calculated using the hypoxanthine-guanine phosphoribosyltransferase gene as an internal normalizer. The generalized linear model was used to determine differentially expressed genes, by pairwise comparison between ages. Among technical replicates, the coefficient of variation ranged from 1.0 to 5.2% and was lower than the variation observed between biological replicates (2.1–12.9%). IGF1 demonstrated significantly lower expression in the 3-year-old age class than in weanlings and yearlings, but the 10-year-old age class displayed a significantly higher level than 2- and 3-year-old age classes. Expression of IGFBP5 was highest in weanlings compared with all other age classes. Expression of MSTN was significantly higher in weanlings than in other age classes, whereas 10-year-old horses had an intermediate level of expression, but significantly different from yearlings, 2- and 3-year-old fillies. Finally, expression of MYH1 was lower in 2- and 10-year-old horses than in weanlings and yearlings, whereas 3-year-old fillies demonstrated an intermediate level of expression. Differential expression patterns observed in this preliminary study provide insight into the physiological changes occurring throughout the life span of horses. These patterns could also help explain the variation in performance and endurance between individuals at different developmental stages.     

Hepatic abscesses in three horses

Hepatic abscesses were diagnosed in 3 adult horses. Two were < 4 years old and had evidence of concurrent immune-mediated conditions, including aseptic arthritis, immune-mediated thrombocytopenia, and immune-mediated anemia. Predisposing factors for hepatic abscess formation in these horses included prior abdominal surgery, proximal duodenitis/jejunitis, inflammatory bowel disease, and a penetrating foreign body in the large colon. Serum hepatic enzyme activities were within or slightly greater then reference limits in all 3 horses. The most pronounced and consistent abnormalities on CBC and serum biochemical analyses were hyperproteinemia, hyperglobulinemia, and a decreased albumin-to-globulin concentration ratio. Hepatic ultrasonography identified hepatic abscesses in all 3 horses. A variety of bacteria were isolated from these abscesses, including Staphylococus aureus and Bacteroides fragilis. One horse developed septic tibiotarsal arthritis, presumably as a result of intermittent bacteremia. Despite aggressive medical treatment, all horses were euthanatized because of a worsening condition and poor prognosis.     

Effect of subacute oral doses of nivalenol on immune and metabolic defence systems in mice

Nivalenol (NIV) is a toxic Fusarium secondary trichothecene metabolite occurring naturally in cereal grains. In order to evaluate the no observed adverse effect level (NOAEL), we tested the effects of a large array of oral doses of this toxin for responses on plasma biochemistry, the immune system and hepatic drug metabolism in mice. C57Bl6 mice received oral doses of toxin (0.014, 0.071, 0.355, 1.774 or 8.87 mg/kg bw) 3 days a week for 4 weeks. Only the highest dose of NIV induced an increase in plasma phosphate, decreases in plasma urea and immunoglobulin M and additional changes like increases in plasma alkaline phosphatase and immunoglobulin G. Interleukin 4 production was increased in cultured murine splenocytes. Regarding liver drug metabolising enzymes, the only glutathione transferase activity accepting 1-chloro-2,4-dinitro-benzene as substrate was transiently increased in mice receiving low doses (0.071 and 0.355 mg/kg bw) of NIV. Regarding the cytochrome P450 monooxygenases, no significant change was observed in ethoxyresorufin O-deethylase activity whereas both methoxyresorufin and pentoxyresorufin O-dealkylase activities were decreased by 38-45% for the highest dose (8.87 mg/kg bw) of NIV. However, when analysed by Western blot analysis, the protein expression of mouse P450 1a, 2b, 2c, 3a and 4a subfamilies was unchanged in animals receiving NIV. In conclusion, the NOAEL of this toxin in our study was 1.774 mg/kg bw, corresponding to an exposure to 5 ppm contaminated food. Indeed hepatotoxicity appears in the only mice treated with a five fold higher oral dose of 8.87 mg/kg bw of NIV. Such exposure levels appear to be by far higher than the maximal natural occurrence measured in European cereals, known to range from 0.34 to 1.86 ppm.     

Impact of age on hepatic cytochrome P450 of domestic male Camborough‐29 pigs

Swine is not only an important species in veterinary medicine research but also a popular animal model for human drug discovery. It is valuable to understand the impact of pig age on abundance and activity of porcine hepatic cytochrome P450 (CYP450). Liver microsomes were prepared from Camborough‐29 intact male pigs at the age of 1 day and 2 weeks and the castrated male pigs at the age of 5, 10, and 20 weeks. Hepatic CYP450 content in the liver microsomes was measured using a UV/visible spectroscopic method. The activities of CYP450s were evaluated by metabolism of phenacetin, coumarin, tolbutamide, bufuralol, chlorzoxazone, and midazolam. The porcine hepatic CYP450 content increased with age with a plateau between age 2 and 5 weeks. Activities of all CYP450 enzymes increased with age of pigs too. The bufuralol 1’‐hydroxylase showed the highest hepatic activities compared with other CYP enzymes at all ages of pigs. The average activities at the age of 20 weeks were about five times higher than those at the age of 5 weeks for most of the CYP enzymes. With compensation of the ratio of liver to body weights, the overall CYP450 metabolism capability of the pigs may be peaked around ages of 10 to 20 weeks. Those findings suggest that metabolism can be significantly different in growing phase of pigs and that the age may be an important factor in porcine medicine evaluation and pig model development.     

Racing performance after arthroscopic removal of apical sesamoid fracture fragments in Thoroughbred horses age < 2 years: 151 cases (1989--2002)

REASONS FOR PERFORMING STUDY: Studies on arthroscopic removal of apical proximal sesamoid fracture fragments in Thoroughbred (TB) horses age > or = 2 years have reported a high success rate. However, there are no reports documenting the racing prognosis of TB horses that undergo such surgery as weanlings or yearlings. OBJECTIVES: To describe the incidence of apical proximal sesamoid fractures in immature TB horses, age < 2 years and determine probability and quality of racing performance after arthroscopic removal of such fractures in 151 TB weanlings and yearlings. METHODS: The medical records of TB horses age < 2 years that underwent arthroscopic surgery for removal of apical proximal sesamoid fracture fragments were reviewed. Follow-up information was obtained from race records. Student's t tests were used to compare performance variables of operated racehorses to that of their maternal siblings. RESULTS: Ninety-two percent (139/151) of fractures occurred in the hindlimbs and 8% (11/151) in the forelimbs (fracture of both fore- and hindlimb, n = 1). Horses with forelimb fractures had a greatly reduced probability of racing (55%) compared to those with hindlimb fractures (86%). Overall, 84% of the horses raced post operatively and had performance records similar to that of their maternal siblings, 78% (787/1006) of which raced. CONCLUSIONS: Arthroscopic removal of apical proximal sesamoid fracture fragments in TB weanlings and yearlings carries an excellent prognosis for racing in horses with hindlimb fractures and a reduced prognosis in those with forelimb fractures. Medial fractures of the forelimb carry the worst prognosis. POTENTIAL RELEVANCE: The determination of prognosis increases knowledge on apical sesamoid bone fractures and potential for arthroscopic restoration of the ability to race; and enables the value of yearlings for subsequent sale to be established.     

Comparison of hepatic in vitro metabolism of the pyrrolizidine alkaloid senecionine in sheep and cattle

OBJECTIVE: To compare hepatic metabolism of pyrrolizidine alkaloids (PAs) between sheep and cattle and elucidate the protective mechanism of sheep. SAMPLE POPULATION: Liver microsomes and cytosol from 8 sheep and 8 cattle. PROCEDURE: The PA senecionine, senecionine N-oxide (nontoxic metabolite) and 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP; toxic metabolite) were measured in microsomal incubations. The kcat (turnover number) was determined for DHP and N-oxide formation. Chemical and immunochemical inhibitors were used to assess the role of cytochrome P450s, flavin-containing monooxygenases (FMOs), and carboxylesterases in senecionine metabolism. The CYP3A, CYP2B, and FMO concentrations and activities were determined, in addition to the role of glutathione (GSH) in senecionine metabolism. RESULTS: DHP concentration did not differ between species. Sheep formed more N-oxide, had higher N-oxide kcat, and metabolized senecionine faster than cattle. The P450 concentrations and isoforms had a large influence on DHP formation, whereas FMOs had a large influence on N-oxide formation. In cattle, CYP3A played a larger role in DHP formation than in sheep. FMO activity was greater in sheep than in cattle. Addition of GSH to in vitro microsomal incubations decreased DHP formation; addition of cytosol decreased N-oxide formation. CONCLUSIONS AND CLINICAL RELEVANCE: Hepatic metabolism differences alone do not account for the variation in susceptibility seen between these species. Rather, increased ruminal metabolism in sheep appears to be an important protective mechanism, with hepatic enzymes providing a secondary means to degrade any PAs that are absorbed from the rumen.     

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.     

Indices of oxidative stress in blood and pulmonary epithelium lining fluid in horses suffering from recurrent airway obstruction.

To test the hypothesis that reactive oxygen species could be associated to the lower airway disorders occurring in horses suffering from recurrent airway obstruction (RAO), indices of oxidative stress were studied in blood and pulmonary epithelium lining fluid in 5 RAO horses either in clinical remission or 24 h after the onset of a crisis of bronchospasm and in 5 healthy horses. Venous blood and bronchoalveolar lavage fluid (BALF) samples were collected and analysed for reduced glutathione (GSH), oxidised glutathione (GSSG), total glutathione (TGSH), glutathione redox ratio (GRR) in blood haemolysate and pulmonary epithelium lining fluid (PELF). The haemolysate concentrations of GSH, GSSG, TGSH and GRR were similar in the 3 groups. The PELF glutathione status was significantly different in the RAO horses in acute crisis compared to healthy horses, indicating the occurrence of an oxidative stress. When RAO horses were in crisis their GSH and TGSH remained unchanged but their GSSG and GRR were significantly increased compared to the remission. These results support the hypothesis that oxidative stress is associated with lower airway disorders occurring in horses suffering from RAO.     

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.     

Serum-free culture of adult chicken hepatocytes; morphological and biochemical characterisation

The morphological and biochemical characterisation of adult chicken hepatocytes in a serum-free culture are described. When cultured in positively charged plastic dishes, chicken hepatocytes formed a monolayer cell sheet. The monolayer morphology of these chicken hepatocytes was quite distinct from the spheroid shape of rat hepatocytes cultured under similar conditions. Electron microscopy showed that the cytoplasmic organelles of chicken hepatocytes were well preserved in vitro. Two-dimensional gel electrophoresis showed that the chicken hepatocytes secreted liver-specific proteins. Several enzymes of glucose-6-phosphatase, cytochrome P-450 or glutathione S-transferase, involved in metabolic and biotransformation pathways in the liver, were retained in the chicken hepatocytes in a serum free condition. These findings suggest that the primary culture of adult chicken hepatocytes with a serum-free culture system could be useful to study the hepatic metabolic pathway in the chicken and its response to various chemicals.     

Diurnal variation and age differences in the biochemical markers of bone turnover in horses

Biochemical markers of bone turnover provide sensitive, rapid, and noninvasive monitoring of bone resorption and formation. Serum concentrations of osteocalcin (OC) reflect rates of bone formation, and urinary concentrations of the pyridinium crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpd) are specific and sensitive markers of bone resorption. These markers are age-dependent and are used to detect and monitor changes in the rates of bone turnover in a variety of orthopedic diseases in humans and may prove to have similar application in horses. This study examined age differences and diurnal variation in OC, Pyd, and Dpd in eight adult geldings and seven weanling colts. Blood and urine were collected at regular intervals over 24 h. Serum OC and cortisol, and urinary Pyd and Dpd were analyzed. Mean 24-h concentrations of cortisol and all three markers were higher (P<.003) in weanlings than adults. Significant 24-h variation was observed in adult gelding OC, Pyd, and Dpd concentrations (P< .02). Adult OC concentrations were highest between 2400 and 0900; Pyd and Dpd peaked between 0200 and 0800. Similar patterns of bone turnover were observed in weanling values, but they were not significant (P>.17) owing to greater variability between individuals. Cortisol secretion varied (P<.001) over 24 h in both adults and weanlings and, thus, did not seem to be responsible for greater variability in markers of bone turnover between weanlings. These data demonstrate that diurnal rhythms exist for serum OC and urinary Pyd and Dpd in adult horses, as reported in humans, and that sample timing is an important consideration in future equine studies using these markers.     

Pulmonary driving pressure as a pulmonary function test in horses

Pulmonary Driving Pressure (PDP) is defined as the difference between the pulmonary artery pressure and the pulmonary capillary wedge pressure. Pulmonary driving pressure is a measure of alveolar ventilation. This parameter was determined in 20 normal horses. The mean value was 10.0 +/−2.37 mm Hg. The PaO2 in these horses varied between 98 and 110 mm Hg. In two of these 20 horses, pulmonary driving pressure was determined 10 timesconsecutively. The obtained values were within very narrow limits for the respective horses indicating the reproducibility of the technique.     

Early management of race-bred weanlings and yearlings on farms

A total of 58 Thoroughbred and Quarter Horse farms that managed 1,987 weanlings and yearlings responded to a survey designed to better characterize early management of racing prospects. Average age at weaning was 5.5 months and over half of all farms kept almost three-fourths of all weanlings to be placed in pre-race training. Variation in feeding practices was evident and while well over half of all farms provided balanced nutrient supply to young horses, 20% to 40% likely fed unbalanced diets. An obvious preference existed for semi-confinement in young horses with plenty of free exercise. The majority of farms reported that young prospects were fed and managed for a moderate rate of growth. Forced exercise occurred to a much larger extent with yearlings than weanlings and 40% of farms described the footing as soft, but not deep. Response to the prevalence of developmental orthopedic diseases appeared somewhat guarded, and average injury rate was low on farms that attributed much of injury to horses playing too hard. Technological advancements such as photoperiod manipulation in broodmares were widely used, while valuable tools such as body condition scoring were utilized to a lesser extent.     

柞蚕饰腹寄蝇不同地理种群的杀虫剂靶标酶和解毒酶活性分析

昆虫通过降低靶标酶敏感性及增强对杀虫剂的代谢能力产生抗药性。蝇毒磷是防治柞蚕饰腹寄蝇(Blepharipa tibia-lis Chao)的常用有机磷杀虫剂,为探讨柞蚕饰腹寄蝇不同地理种群对蝇毒磷的抗药性分化程度,分析来自辽宁省瓦房店市、凤城市、庄河市、开原市和西丰县的5个柞蚕饰腹寄蝇地理种群体内的乙酰胆碱酯酶(AChE)、谷胱甘肽S-转移酶(GST)、细胞色素P450(CYP450)和羧酸酯酶(CarE)4种酶的活性及蝇毒磷对这些酶活性的体外抑制率。结果表明:来自瓦房店市和凤城市的柞蚕饰腹寄蝇地理种群的AChE比活力及蝇毒磷对酶活性的体外抑制率均显著高于其它3个地理种群;瓦房店市地理种群的GST比活力显著高于其它4个地理种群,蝇毒磷对酶活性的体外抑制率显著高于除庄河市地理种群外的其它3个地理种群;庄河市地理种群的CYP450比活力显著高于来自瓦房店市、凤城市和西丰县的3个地理种群,但与开原市地理种群相比差异不显著,蝇毒磷对瓦房店市地理种群的CYP450活性的体外抑制率显著高于其它4个地理种群;瓦房店市与凤城市地理种群的CarE比活力均显著高于来自庄河市、开原市和西丰县的3个地理种群;蝇毒磷对瓦房店市和凤城市地理种群的CarE活性的体外抑制率显著高于庄河市地理种群,对其它地理种群间的CarE活性的体外抑制率差异不显著。根据以上检测结果,推测来自庄河市的柞蚕饰腹寄蝇地理种群对蝇毒磷的抗性相对较强,而来自瓦房店市的柞蚕饰腹寄蝇地理种群对蝇毒磷的抗性相对较弱。     

Effect of oral administration of excessive iron in adult ponies

OBJECTIVE: To evaluate the potential of excess dietary iron to cause hepatic lesions similar to those described in horses with suspected iron toxicosis or hemochromatosis. DESIGN: Prospective study. ANIMALS: 6 adult male ponies. PROCEDURE: 4 ponies received 50 mg of iron/kg (22.7 mg/lb) of body weight each day by oral administration of ferrous sulfate, which contained 20% elemental iron; 2 ponies received only the carrier (applesauce). Complete blood counts, serum biochemical analyses, and hepatic tissue biopsies were performed, and serum iron concentrations were measured. Blood and tissue samples were obtained at days 0 and 2, and at the end of weeks 1, 3, 6, and 8 after administration of iron was initiated. Treatment was discontinued after 8 weeks, and hepatic iron concentrations were measured at 28 weeks. RESULTS: Hepatic iron concentrations, serum iron concentrations, percentage saturation of transferrin, and serum ferritin concentrations were increased, compared with baseline and control concentrations, by week 8. Adverse clinical signs or histologic lesions in the liver were not detected in any ponies. At 28 weeks, hepatic iron concentrations had decreased. CONCLUSIONS AND CLINICAL RELEVANCE: Histologic lesions were not seen in the hepatic biopsy specimens obtained from the ponies treated with ferrous sulfate. It was concluded that it would be unlikely for iron toxicosis to develop in adult ponies or horses during a period of < 8 weeks when food or water contained increased amounts of iron. It is suspected that previous reports of hepatopathies in animals with hemosiderin accumulation may represent a primary hepatopathy with secondary hemosiderin accumulation, especially if the only source of iron is via oral consumption.     

Effect of nutritional antioxidant supplementation on systemic and pulmonary antioxidant status,airway inflammation and lung function in heaves-affected horses

An oxidant/antioxidant imbalance in favour of oxidants has been identified as playing a decisive role in the pathogenesis of chronic inflammatory airway diseases. Nutritional antioxidant supplementation might reduce oxidative damage by enhancement of the antioxidant defence, thereby modulating inflammatory processes. In a placebo-controlled, blind study, it was tested whether a dietary antioxidant supplement administered for 4 weeks would improve lung function and reduce airway inflammation in heaves-affected horses. Eight horses in clinical remission of heaves were investigated at rest and after a standardised exercise test before and after treatment with an antioxidant supplement (consisting of a mixture of natural antioxidants including vitamins E and C and selenium from a variety of sources) or placebo (oatfeed pellets without additive). Pulmonary function and exercise tolerance were monitored; systemic and pulmonary lining fluid uric acid, glutathione and 8-epi-PGF(2alpha) were analysed, and bronchoalveolar lavage (BAL) cytology and inflammatory scoring of the airways were performed. The antioxidant treatment significantly improved exercise tolerance and significantly reduced endoscopic inflammatory score. Plasma uric acid concentrations were significantly reduced, suggesting downregulation of the xanthine-dehydrogenase and xanthine-oxydase pathway. Haemolysate glutathione showed a nonsignificant trend to increase, while plasma 8-epi-PGF(2alpha) remained unchanged. Pulmonary markers and BAL cytology were not significantly affected by antioxidant supplementation. The present study suggests that the antioxidant supplement tested modulated oxidant/antioxidant balance and airway inflammation of heaves-affected horses.