Biochemical, functional, and histopathologic characterization of lomustine-induced liver injury in dogs

Andrea M. Dedeaux, Brian K. Flesner, Jennifer M. Reinhart, Ingeborg M. Langohr, Roman Husnik, Shawn N. Geraci, Joseph Taboada, Nathalie Rademacher, Lori A. Thombs, Jeffrey N. Bryan, Lauren A. Trepanier, Bonnie B. Boudreaux

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs. ANIMALS 10 healthy purpose-bred sexually intact female hounds. PROCEDURES Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone. RESULTS 7 of the 10 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score. CONCLUSIONS AND CLINICAL RELEVANCE In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.

Original languageEnglish (US)
Pages (from-to)810-820
Number of pages11
JournalAmerican journal of veterinary research
Volume81
Issue number10
DOIs
StatePublished - Oct 2020

ASJC Scopus subject areas

  • veterinary(all)

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