Time-dependent hepatic histopathological and biochemical changes following a single dose of methylprednisolone aetate in dogs

Long-acting corticosteroids, such as methylprednisolone acetate, are commonly used in veterinary medicine due to their prolonged anti-inflammatory and immunosuppressive effects. Despite their extensive clinical use, evidence on the hepatic safety profile of long-acting corticosteroid formulations remains insufficient and requires further investigation. This study investigated the biochemical and histopathological changes in the liver following a single intramuscular injection of long-acting methylprednisolone acetate at 2 mg kg⁻¹ in seven healthy beagle dogs, monitored over a 56-day period. Serum enzyme activities – alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) – were measured every seven days, while ultrasound-guided liver biopsies were obtained on days 0, 14, 28, and 56. Tissue samples were evaluated using haematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and immunohistochemical staining. Significant increases in GGT and ALP were observed, peaking at around day 14, followed by gradual normalisation by day 56. Histological evaluation revealed hepatocellular changes, including swelling, cytoplasmic vacuolation, and marginal nuclear displacement. Neutrophil counts and hepatic stellate cell numbers showed no significant differences across time points. This work extends current knowledge by documenting the time-dependent progression and partial recovery of hepatic alterations following a single dose of long-acting methylprednisolone acetate in dogs. The results highlight the importance of monitoring liver responses and provide new insight into the subclinical hepatic effects of depot corticosteroids, with potential implications for safer therapeutic decision-making in veterinary practice.