Administration of miltefosine and meglumine antimoniate in healthy dogs: clinicopathological evaluation of the impact on the kidneys.
In canine leishmaniosis (CanL), kidneys are affected in virtually all dogs. Treatment of CanL is limited in Europe to meglumine antimoniate and miltefosine. This study evaluated the pharmacological, toxicological, and pathological effects of both drugs in healthy beagle dogs. Four male and four female dogs were divided into two groups. The animals in Group 1 were administered an oral solution of 2% of miltefosine at 2 mg/kg b.w. once a day, for twenty-eight days. The animals in Group 2 were administered a preparation of meglumine antimoniate at 100 mg/kg b.w. subcutaneously once a day for twenty-eight days. After treatment, all dogs were followed-up for a further twenty-eight days. Dogs were observed daily and clinically examined ten times throughout the study. On days -1 and 55 a renal biopsy was performed on all dogs and analyzed by light microscopy, immunofluorescence, and electron microscopy. All the examinations failed to demonstrate any lesions in the miltefosine-treated dogs. Conversely, all the meglumine antimoniate-treated dogs demonstrated severe tubular damage, characterized by tubular cell necrosis and apoptosis. In conclusion, although no clinical signs of renal disease were evident, the use of meglumine antimoniate in the pharmacological treatment approach of CanL-affected dogs should be carefully considered.
Bianciardi
Paolo
P
paolobianci@libero.it
Brovida
Claudio
C
Valente
Marialuisa
M
Aresu
Luca
L
Cavicchioli
Laura
L
Vischer
Claudia
C
Giroud
Lucie
L
Castagnaro
Massimo
M
D000818:Animals; D000981:Antiprotozoal Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D005260:Female; D005455:Fluorescent Antibody Technique; D006651:Histocytochemistry; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D007896:Leishmaniasis; D008297:Male; D008536:Meglumine / Q000633:toxicity*; D000077485:Meglumine Antimoniate; D008854:Microscopy, Electron; D009942:Organometallic Compounds / Q000633:toxicity*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000633:toxicity; D011897:Random Allocation; D018675:Toxicity Tests
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010767:Phosphorylcholine; C039128:miltefosine; D008536:Meglumine; D000077485:Meglumine Antimoniate