Oxidative damage of canine erythrocytes after treatment with non-steroidal anti-inflammatory drugs

Abstract

Objective To investigate oxidative erythrocyte damage in dogs treated with different non-steroidal anti-inflammatory drugs.

Material and methods Case-controlled prospective observational study using blood obtained from dogs presenting for lameness examinations or standard surgical procedures to a private referral clinic. Sampling was performed from April 2018 to July 2019. Groups comprised dogs receiving either metamizole (dipyrone) (22 dogs), carprofen (20 dogs) or meloxicam (20 dogs) for a minimum of 10 days. Dogs with gastrointestinal hemorrhage were excluded from the study. A complete hematological, as well as a basic biochemical profile were performed in every dog. Pappenheim stained blood smears were evaluated for eccentrocytes and brilliant cresyl blue stained smears for Heinz bodies. EDTA blood was frozen at –80°C immediately after sampling for measurement of superoxide dismutase and gluthathione peroxidase activity at an external laboratory. Hemoglobin concentration, superoxide dismutase and gluthathione peroxidase activities, reticulocyte count, eccentrocyte and Heinz body numbers were determined prospectively as key parameters for further statistical assessment with Kruskal-Wallis test and Dunn’s multiple comparisons test.

Results Dogs receiving metamizole showed a significant increase in eccentrocyte (median 14.5/500 cells vs. 0/500 cells in the other groups, p < 0.0001) and reticulocyte number (median 191.4 × 10⁹/l vs. 31.6–37.9 × 10⁹/l, p < 0.0001) and a significant decrease in hemoglobin concentration (median 8.4 mmol/l vs. 10.1–10.5 mmol/l, p < 0.0003). No significant difference in superoxide dismutase and gluthathione peroxidase activities was observed between dogs receiving metamizole and the other groups. Heinz bodies were not found in any of the dogs.

Conclusion Treatment with metamizole for 10 or more days resulted in decreased hemoglobin concentration, eccentrocytosis and reticulocytosis in dogs in this study. This might be a sign of increased oxidative damage caused by this drug.

Clinical significance Prolonged metamizole therapy should be evaluated critically in patients already affected by severe illness or underlying anaemia.

Zusammenfassung

Gegenstand und Ziel Untersuchung des oxidativen Erythrozytenschadens bei Hunden, die mit unterschiedlichen nicht steroidalen Antiphlogistika behandelt wurden.

Material und Methoden Die prospektive Fall-Kontroll-Studie erfolgte von April 2018 bis Juli 2019 mit Hunden, die zu Lahmheitsuntersuchungen oder für Routineoperationen in einer Überweisungsklinik vorgestellt wurden. Die Studiengruppen bestanden aus Hunden, die entweder Meloxicam (20 Hunde), Carprofen (20 Hunde) oder Metamizol (Dipyron) (22 Hunde) für mindestens 10 Tage erhalten hatten. Hunde mit gastrointestinalen Blutungen wurden ausgeschlossen. Jeder Hund unterlag einer vollständigen hämatologischen sowie klinisch-chemischen Untersuchung. Zur Untersuchung auf Ekzentrozyten dienten mit Pappenheim-Färbung gefärbte und für Heinz-Innenkörperchen mit Brilliantkresylblau gefärbte Blutausstriche. EDTA-Blut wurde sofort nach Probenentnahme bei –80°C eingefroren und zur weiteren Untersuchung der Superoxid-Dismutase- und Glutathion-Peroxidase-Aktivität auf Trockeneis an ein Fremdlabor versendet. Hämoglobinkonzentration, Superoxid-Dismutase-, Glutathion-Peroxidase-Aktivität sowie Retikulozyten-, Ekzentrozyten- und Heinz-Innenkörperchen-Zahl wurden prospektiv als Schlüsselparameter für die statistische Auswertung mittels Kruskal-Wallis-Test und Dunn-Nachtest bestimmt.

Ergebnisse Hunde, die Metamizol erhielten, hatten eine signifikant höhere Ekzentrozyten- (Median 14,5/500 Zellen vs. 0/500 Zellen in den anderen Gruppen, p < 0,0001) und Retikulozytenzahl (Median 191,4 × 10⁹/l vs. 31,6–37,9 × 10⁹/l, p < 0,0001) sowie signifikant niedrigere Hämoglobinwerte (Median 8,4 mmol/l vs. 10,1–10,5 mmol/l, p < 0,0003). Die Aktivitäten der Superoxid-Dismutase und der Glutathion-Peroxidase differierten zwischen den Gruppen nicht signifikant. Heinz-Innenkörperchen wurden nicht gefunden.

Schlussfolgerung Die Studie zeigte, dass eine Behandlung von Hunden mit Metamizol über 10 oder mehr Tage zu erniedrigtem Hämoglobinwert sowie erhöhter Retikulozyten- und Ekzentrozytenanzahl führen kann. Dies könnte ein Hinweis auf durch Metamizol verursachten oxidativen Schaden an Erythrozyten sein.

Klinische Signifikanz Eine länger andauernde Metamizoltherapie sollte bei anämischen und schwer kranken Hunden kritisch evaluiert werden.

Key words

Dog - eccentrocytes - metamizole - dipyrone - carprofen - meloxicam

Schlüsselwörter

Hund - Ekzentrozyten - Metamizol - Dipyron - Carprofen - Meloxicam

Publikationsverlauf

Eingereicht: 22. September 2020

Angenommen: 11. April 2021

Artikel online veröffentlicht:
03. Dezember 2021

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