Effects of Long-Term Carprofen and Omeprazole Administration in C57BL/6J Mice.

Abstract

Osteoarthritis is the leading cause of disability in the United States and affects approximately half of adults over the age of 65. Many osteoarthritis patients take nonsteroidal anti-inflammatory drugs (NSAIDs) on a long-term basis, often concurrently with proton pump inhibitors (PPIs), such as omeprazole, to prevent gastric ulceration. Mice (Mus musculus) are a commonly used animal model of osteoarthritis. There are little data regarding long-term administration of NSAIDs or coadministration of PPIs and NSAIDs in mice. This study sought to determine if administration of carprofen, a commonly used veterinary NSAID, has adverse effects when administered for 21 days and if coadministration of omeprazole reduces the incidence of adverse effects. Four groups of C57BL/6J male (n = 5/group) and female (n = 5/group) mice were weighed daily and administered 10 mg/kg carprofen and 8.2 mg/kg omeprazole, 10 mg/kg carprofen, 8.2 mg/kg omeprazole, or control suspension once daily by oral gavage for 21 days. All mice were euthanized, and complete blood count (CBC), serum chemistry, fecal occult blood, and pyloric histopathology and gastritis scoring were conducted. All animals remained clinically healthy for the duration of the study. White blood cell counts (WBCs) and platelets were significantly lower in the carprofen and omeprazole group. Neutrophil counts were significantly lower in the carprofen and omeprazole and the carprofen groups. Compared with the control group, albumin was significantly higher in the carprofen group. Fecal occult blood tests were negative for all animals. No animals had pyloric mucosal ulceration, and gastritis scores were not significantly different between groups. Body weight significantly decreased for all groups over time, with no significant differences among treatment groups. Carprofen and omeprazole may be safely administered to C57BL/6J mice for 21 days but may induce significant changes in CBC and serum chemistry.