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  • Author or Editor: Charles G. Plopper x
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Abstract

Objective—To determine hepatic and pulmonary phase-I and phase-II enzyme activities in horses.

Sample population—Pulmonary and hepatic tissues from 22 horses that were 4 months to 32 years old.

Procedure—Pulmonary and hepatic tissues from horses were used to prepare cytosolic (glutathione S-transferase and soluble epoxide hydrolase) and microsomal (cytochrome P450 monooxygenases) enzymes. Rates of microsomal metabolism of ethoxyresorufin, pentoxyresorufin, and naphthalene were determined by high-performance liquid chromatography. Activities of glutathione S-transferase and soluble epoxide hydrolase were determined spectrophotometrically. Cytochrome P450 content was determined by carbon monoxide bound-difference spectrum of dithionite-reduced microsomes. Activity was expressed relative to total protein concentration.

Results—Microsomal protein and cytochromeP450 contents were detectable in all horses and did not vary with age. Hepatic ethoxyresorufin metabolism was detected in all horses; by comparison, pulmonary metabolism of ethoxyresorufin and hepatic and pulmonary metabolism of pentoxyresorufin were detected at lower rates. Rate of hepatic naphthalene metabolism remained constant with increasing age, whereas rate of pulmonary naphthalene metabolism was significantly lower in weanlings (ie, horses 4 to 6 months old), compared with adult horses. Hepatic glutathione S-transferase activity (cytosol) increased with age; however, these changes were not significant. Pulmonary glutathione S-transferase activity (cytosol) was significantly lower in weanlings than adult horses. Hepatic and pulmonary soluble epoxide hydrolase did not vary with age of horses.

Conclusions and Clinical Relevance—Activity of cytochrome P450 isoforms that metabolize naphthalene and glutathione S-transferases in lungs are significantly lower in weanlings than adult horses, which suggests reduced ability of young horses to metabolize xenobiotics by this organ. (Am J Vet Res 2000;61:152–157)

Full access
in American Journal of Veterinary Research

SUMMARY

Interstitial and bronchointerstitial pulmonary patterns are commonly observed in thoracic radiographs of Thoroughbreds. Prominent interstitial and bronchointerstitial pulmonary patterns are observed in clinically normal horses, and in horses with respiratory tract disease. Until recently, the relevance of these pulmonary patterns was not known. Previous studies indicated that bronchiolitis, bronchiolar epithelial hyperplasia, epithelial metaplasia, and bronchial arteriolar recruitment correlated strongly with the prominence of the interstitial and bronchointerstitial pulmonary patterns observed radiographically. We examined the content and distribution of collagen in the lungs of 7 clinically normal Thoroughbreds in race training. After standardized fixation, lung tissue was treated with a compound that selectively stains collagen. Standard morphometric techniques were used to determine the volume density of parenchymal tissue and parenchymal airspace, mean linear intercept (estimate of alveolar size), alveolar surface area-to-volume ratio, percentage of parenchyma composed of collagen, percentage of airway wall composed of collagen, and airway wall thickness. These values were compared with radiographic and histopathologic scores obtained from the same horses. The volume density of parenchymal tissue and small airway wall thickness correlated strongly with the prominence of the bronchial and bronchointerstitial pulmonary patterns observed radiographically. Small airway thickness was also highly correlated with the perceived prominence of the interstitial pulmonary patterns observed radiographically, and morphometric estimates of parenchymal tissue and parenchymal collagen. There were also strong correlations between the volume density of parenchymal tissue, the percentage of parenchymal collagen, peribronchiolar mononuclear cell infiltrates, and bronchiolar mucosal plication estimates. In horses with more prominent bronchiolar mucosal plication, there was a strong direct relation to the observed prominence of peribronchiolar and submucosal blood vessels, and the bronchial and bronchointerstitial patterns observed radiographically. Horses with prominent peribronchiolar mononuclear cell infiltrates also had more obvious interstitial and bronchointerstitial pulmonary patterns observed radiographically. There also was a direct correlation between the percentage of parenchymal collagen and the observed prominence of peribronchiolar and submucosal blood vessels in these horses. In all horses, there was a strong negative correlation between the estimated average alveolar size and the observed severity of the vascular and bronchial patterns observed radiographically.

Four horses with the greatest estimated airway wall and interalveolar collagen had more prominent interstitial and bronchointerstitial densities and histopathologic evidence of bronchiolitis. These horses had evidence of epithelial basement membrane disruption, with disorganized collagen fibers running between the adventitial layer and the epithelial basement membrane. Amounts of collagen were greater in the adventitia and interalveolar septa, with the fibers appearing larger and more coarse and disorganized. In horses with the greatest percentage of interalveolar septal collagen, accumulations of collagen were larger in the interalveolar septal tips. These findings suggest that horses with prominent interstitial and bronchointerstitial pulmonary patterns radiographically have undergone previous episodes of pulmonary injury, which has resulted in deposition of increased amounts of collagen in interalveolar septa and airway walls.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine whether oral administration of erythromycin alters the inflammatory response to bronchoalveolar lavage (BAL) in young horses.

Animals

12 healthy, unweaned, mixed-breed foals of either sex, between 2 and 4 months old.

Procedure

BAL was performed; 250 ml of phosphate-buffered saline solution (300 mOsm, pH 7.4) was administered in 50-ml aliquots. Foals were carefully monitored for 4 days, then erythromycin base (25 mg/kg of body weight, PO, q 12 h) was given to foals of the treated group. After 4 days, foals were re-anesthetized, and the same lung was relavaged. Cytologic examination was performed on BAL fluid (BALF) samples from both groups of foals. At 12 hours after administration of the final dose, erythromycin A and anhydroerythromycin A concentrations were determined in plasma of treated foals.

Results

In the second BALF sample from the same lung of control foals, percentage of neutrophils was significantly increased (3 ± 38.0%), compared with that from erythromycin-treated foals (4.88 ± 3.66%, P < 0.05), and was associated with apparent decrease in the ability of BALF cells from erythromycin-treated foals to migrate toward a chemoattractant source. Significantly fewer BALF cells adhered to a cell culture substratum after erythromycin treatment of foals. Erythromycin A was not detected in plasma of any treated foal at the time of the second BAL; anhydroerythromycin A, a degradation product of erythromycin, was detected in plasma of 5 of 6 foals (mean concentration, 0.2 ± 0.06 µg/ml).

Conclusion and Clinical Relevance

BAL induces neutrophilic inflammation, which persists for at least 4 days in the lungs of young horses. Erythromycni (25 mg/kg, PO, q 12 h) diminishes this inflammatory response through a mechanism that may involve alteration of BALF cell function. Degradation of erythromycin to biologically active products or presence of parent drug in pulmonary secretions may be responsible for alterations in pulmonary lavage cell Chemotaxis and adherence. Erythromycin administered orally to foals at clinically relevant doses appears to have nonantimicrobial effects that may interfere with host cell metabolism and decrease inflammatory reponses in airways. (Am J Vet Res 1997;58:56–61)

Free access
in American Journal of Veterinary Research