Abstract

Elasmobranchs are subject to inflammation secondary to a variety of causes, and possess COX-1 and COX-2, analogous to mammalian COX enzymes. Cyclooxygenase (COX) converts precursor molecules into proinflammatory prostaglandins and leukotrienes such as thromboxane A2 (TXA2). Nonsteroidal anti-inflammatory drugs (NSAIDs), such as the COX-2 selective carprofen, are commonly used to reduce inflammation in many species. TXA2 production by Atlantic stingray cells in vitro was partly reduced by indomethacin, but in vivo COX inhibitor effects have not been studied. We compared blood cell TXB2 production from captive cownose rays (Rhinoptera bonasus) treated with a single intramuscular dose of carprofen (4 mg/kg; n = 10) with untreated cownose ray cells (n = 6). We collected blood samples from carprofen-treated rays at 1, 3, 6, 12, 24, 36, 48, 72, and 96 hours post-administration to establish a pharmacokinetic profile. Blood collected 6 and 24 hour post-administration was assessed for TXB2 production. Maximal TXB2 production was elicited by stimulation of blood cells with the calcium ionophore A23187. Control ray blood was treated with carprofen (4 mg/L) in vitro for comparison with in vivo results. Indomethacin in vitro greatly inhibited TXB2 production from controls. Control cells treated with carprofen in vitro produced reduced amounts of TXB2 indicating a response by these cells to this COX-2 inhibitor. However TXB2 production by carprofen-treated cells was maximal in response to A23187 at both 6 and 24 hours. Carprofen levels were measureable 96 hours post-administration, but this single dose does not reduce TXB2 production in vivo.

* Presenting author