Studies on the effect of phenylbutazone and salicylate on the rates of synthesis of albumin and acute-phase α1-acid glycoprotein by rat liver slices

Jamieson, J.C.; Kutryk, Michael J.B.

doi:10.1016/0006-2944(80)90039-3

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…These were attributed to gastrointestinal ulceration with loss of plasma into the lumen of the gut (Snow et a1 1980). Evidence in rats suggests that decreases in serum protein concentration may also result from phenylbutazone induced inhibition of hepatic synthesis of albumin and acute phase proteins (Jamieson and Kutryk 1980). Our finding that individual serum proteins (albumin, a,-% az-, 8and yglobulins) were decreased by similar amounts during treatment with phenylbutazone is compatible with both of these mechanisms.…”

Section: Discussionsupporting

confidence: 77%

“…Similar, but more profound, changes in total protein and albumin in ponies receiving higher doses of phenylbutazone were reported by Snow et a1 (1979;. Evidence in rats suggests that decreases in serum protein concentration may also result from phenylbutazone induced inhibition of hepatic synthesis of albumin and acute phase proteins (Jamieson and Kutryk 1980). Evidence in rats suggests that decreases in serum protein concentration may also result from phenylbutazone induced inhibition of hepatic synthesis of albumin and acute phase proteins (Jamieson and Kutryk 1980).…”

Section: Discussionsupporting

confidence: 70%

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Biochemical and haematological effects of phenylbutazone in horses

Lees

Creed

Gerring

et al. 1983

Equine Veterinary Journal

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Summary Five matched pairs of horses were used to investigate the effects of phenylbutazone on a range of physiological, biochemical and haematological variables. The drug was given by mouth daily for 15 consecutive days at the manufacturer's recommended dose rates to one group of horses (Group A); the second group (Group B) received equivalent doses of a placebo. For some of the measured parameters, significant changes were recorded in both groups, indicating background instability. Significant decreases in serum total protein, albumin, plasma pH, viscosity and magnesium, and an increase in albumin: globulin ratio occurred in Group A, but not in Group B. These changes were, therefore, attributed to phenylbutazone or its metabolites. Toxicologically, the change in pH is probably unimportant but the decrease in protein concentration may have resulted from a protein losing enteropathy and/or from decreased synthesis in the liver. In one animal which received phenylbutazone, clinical signs of toxicity (lethargy, inappetance, oedema) were observed and evidence of hepatotoxicity and haematological changes were also noted in this horse. It is concluded that recommended dose rates of phenylbutazone should never be exceeded and that the period for which the highest dose (4.4 mg/kg body weight twice daily for four days) is administered should be reduced. In clinical cases, where phenylbutazone toxicity is suspected, measurement of serum or plasma protein concentration might provide an indication of the need to reduce dose levels or stop therapy. Résumé Cinq paires de chevaux comparables ont été utilisés pour rechercher les effets de la phénylbutazone sur un ensemble de variables physiologiques, biochimiques, hématologiques. Le médicament fut administréà un groupe de chevaux (Groupe A), par voie orale, chaque jour durant 15 jours consécutifs; on respectait les posologies recommandées par le fabricant. Un second groupe (Groupe B) recut dans les mêmes conditions un placebo. Pour quelques paramètres, des changements significatif furent constatés dans les deux groupes ce qui indique une instabilité des conditions fixes de l'expérience. Au sein du Groupe A, une diminution significative s̀e produisit pour les protéines totales, pour l'albumine, pour le pH plasmatique, pour la viscosité et pour le magnésium plasmatiques et une augmentation dans le rapport globuline albumines. Les modifications ne se produisirent point au sein du Groupe B. Les changements furent en conséquence attribués à la phénylbutazone ou a ses métabolites. Sur le plan toxicologique, la variation du pH est probablement sans importance; l'abaissement de la concentration en protéines peut résulter d'une entéropathie spoliatrice ou (et) d'une synthèse hépatique diminuée. Chez un animal recevant de la phénylbutazone, des signes cliniques de toxicité (léthargie, oedème et inappétence) furent observés; des signes d'hépatotoxicité et des sanguines furent remarqués chez ce cheval. On en conclue que les posologies recommandées pour la phénylbutazone ne devraient jamais...

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 70%

Biochemical and haematological effects of phenylbutazone in horses

Lees

Creed

Gerring

et al. 1983

Equine Veterinary Journal

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“…teins such as albumin [7,15,17,19]. Con flicting results have been reported regarding the behavior of several nonexported proteins, since some authors found an increase and others a decrease in their levels [9], As re gards the behavior of phases 1 and II detoxi cation enzymes, known to play a very impor tant part in the hepatic biotransformation of endogenous and exogenous compounds [3,13,23], this has never been studied during an AIR.…”

mentioning

confidence: 99%

Study of Biochemical Behavior of Some Exported and Nonexported Hepatic Proteins during an Acute Inflammatory Reaction in the Rat

Mahu¹,

Feldmann²

1984

Enzyme

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Haptoglobin, albumin, glucose-6-phosphatase, p-nitrophenol uridine diphosphate (UDP)-glucuronosyltransferase and cytochrome P-450 were measured in liver microsomes from normal rats and from rats undergoing an acute inflammatory reaction (AIR) induced either by subcutaneous administration of turpentine or by intrapleural injection of calcium pyrophosphate. 24 h after the beginning of the AIR induced by subcutaneous administration of turpentine, haptoglobin and albumin, two exported proteins, had risen to a peak (+313%), and dropped considerably (-52%) whereas nonexported protein levels did not change except for cytochrome P-450, which diminished (-38%). In the same way, intrapleural injection of calcium pyrophosphate was followed after 24 h by significant but smaller variations in haptoglobin (+60%) and cytochrome P-450 (-20%) concentrations. Albumin levels, glucose-6-phosphatase and //-nitrophenol UDP-glucuronosyltransferase activities were unchanged in this experimental model. The drop in cytochrome P-450 under all these conditions and also the diminution of albumin in the first model suggest that all the proteins produced by liver cells might not be synthesized in equal amounts. The decrease in cytochrome P-450 could interfere in hepatic drug metabolism during an AIR.

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“…This could be due to gastric ulceration, loss of plasma into the stomach, or other sites of injury, and the therapeutic effect provided by OME was effective in relieving these symptoms. Studies in rats have shown that PBZ may inhibit hepatic albumin and acute phase protein synthesis, which subsequently leads to a decrease in serum protein concentrations 26 . Albumin is the most abundant protein in equine blood, and its low‐molecular weight leads to a significant reduction in albumin content in horses with inflammatory diseases of the gastrointestinal tract 27 .…”

Section: Discussionmentioning

confidence: 99%

Clinical effects of a combination of phenylbutazone and omeprazole on chronic lameness in Mongolian horses

Wang³

et al. 2023

Equine Veterinary Journal

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BackgroundPhenylbutazone (PBZ) is the most commonly used drug to treat symptoms of lameness in horses; however, it is associated with adverse effects such as gastric ulcer syndrome (EGUS). Interestingly, many practitioners prescribe omeprazole (OME) concurrently with PBZ to prevent the development of EGUS. However, the efficacy and safety of this practice in Mongolian horses with chronic lameness remain unknown.ObjectivesTo evaluate the clinical effects of a combination of PBZ and OME on chronic lameness in Mongolian horses.Study designRandomised block experimental design.MethodsEighteen Mongolian horses with lameness score was ≥3 points, were divided into three treatment groups, with six horses in each group: placebo (CON), PBZ (4.4 mg/kg PO q. 24 h), or PBZ plus OME (4 mg/kg PO q. 24 h; PBZ + OME) in a randomised block design based on the initial lameness score. The horses were treated for 15 days. During this period, weekly gastroscopy, and physiological and biochemical tests were performed.ResultsBoth PBZ (median 1.0, interquartile range [IQR]: 0.8–1.3; p = 0.01) and PBZ + OME (median 1.0, IQR: 1.0–1.0; p = 0.01) significantly decreased the lameness score compared with before administration. In addition, PBZ significantly increased the equine glandular gastric disease (EGGD) score (3.0 ± 0.6, p < 0.001), GT‐17 content (293.4 ± 21.8 pg/mL, p < 0.001), and pepsinogen‐1 (PG1) content (295.3 ± 38.3 ng/mL, p < 0.001) compared with CON or PBZ + OME. However, it significantly reduced the total protein (53.6 ± 1.5 g/L, p < 0.05) and albumin (25.5 ± 1.8 g/L, p < 0.05) contents. Nevertheless, compared with PBZ, PBZ + OME significantly decreased the EGGD score (0.3 ± 0.5, p < 0.001) and significantly increased the gastric fluid pH (7.3 ± 0.5, p < 0.001), total protein content (62.5 ± 4.6 g/L, p = 0.009), and albumin content (29.4 ± 1.1 g/L, p = 0.004). Meanwhile, they significantly diminished the gastrin 17 (GT‐17) (162.0 ± 21.0 pg/mL, p < 0.001) and PG1 (182.4 ± 22.5 ng/mL, p < 0.001) contents.Main limitationsIndividual differences in horses were larger, but the sample size was small. There was larger interval between observations for each index.ConclusionsCompared with PBZ alone, PBZ + OME had no therapeutic effect on chronic lameness; however, it reduced the occurrence of EGGD in Mongolian horses. Horses may be protected against chronic lameness and PBZ‐induced EGGD by increasing the pH value, decreasing serum PG1 and GT‐17 content, and preventing the reduction of myeloperoxidase content.

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Studies on the effect of phenylbutazone and salicylate on the rates of synthesis of albumin and acute-phase α1-acid glycoprotein by rat liver slices

Cited by 6 publications

References 19 publications

Biochemical and haematological effects of phenylbutazone in horses

Biochemical and haematological effects of phenylbutazone in horses

Study of Biochemical Behavior of Some Exported and Nonexported Hepatic Proteins during an Acute Inflammatory Reaction in the Rat

Clinical effects of a combination of phenylbutazone and omeprazole on chronic lameness in Mongolian horses

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