Evaluation of the role of the cyclooxygenase signaling pathway during inflammation in skin and muscle tissues of ball pythons (Python regius)

Abstract

OBJECTIVE To determine degrees of production of cyclooxygenase (COX)-1 and -2 and other mediators of inflammation in noninflamed and inflamed skin and muscle tissues in ball pythons (Python regius). ANIMALS 6 healthy adult male ball pythons. PROCEDURES Biopsy specimens of noninflamed skin and muscle tissue were collected from anesthetized snakes on day 0. A 2-cm skin and muscle incision was then made 5 cm distal to the biopsy sites with a CO2 laser to induce inflammation. On day 7, biopsy specimens of skin and muscle tissues were collected from the incision sites. Inflamed and noninflamed tissue specimens were evaluated for production of COX-1, COX-2, phosphorylated protein kinase B (AKT), total AKT, nuclear factor κ-light-chain-enhancer of activated B cells, phosphorylated extracellular receptor kinases (ERKs) 1 and 2, and total ERK proteins by western blot analysis. Histologic evaluation was performed on H&E-stained tissue sections. RESULTS All biopsy specimens of inflamed skin and muscle tissues had higher histologic inflammation scores than did specimens of noninflamed tissue. Inflamed skin specimens had significantly greater production of COX-1 and phosphorylated ERK than did noninflamed skin specimens. Inflamed muscle specimens had significantly greater production of phosphorylated ERK and phosphorylated AKT, significantly lower production of COX-1, and no difference in production of COX-2, compared with production in noninflamed muscle specimens. CONCLUSIONS AND CLINICAL RELEVANCE Production of COX-1, but not COX-2, was significantly greater in inflamed versus noninflamed skin specimens from ball pythons. Additional research into the reptilian COX signaling pathway is warranted.

A Critical Review on the Pharmacodynamics and Pharmacokinetics of Non-steroidal Anti-inflammatory Drugs and Opioid Drugs Used in Reptiles

“…Four studies investigating COX expression in reptiles were found and the data are summarized in Table 3 . A similar trend was observed in both eastern box turtles and ball python, where significantly higher COX-1 expression was observed in inflamed than non-inflamed tissue, whereas no significant change in COX-2 expression was observed during inflammation ( Royal et al., 2012 ; Sadler et al., 2016 ). However, in the eastern box turtles, COX-2 expression was higher in inflamed than non-inflamed tissue by two-fold although it was not considered significant ( Royal et al., 2012 ).…”

“… N.R. Reference ( Buch et al., 2018 ) ( Buch et al., 2017 ) ( Royal et al., 2012 ) ( Sadler et al., 2016 ) ( Sadler et al., 2016 ) a Referring to COX expression or activity during inflammation in comparison to normal conditions. b Four suffered from head trauma, while one suffered from maggot infestation which led to amputation N.R., not reported.…”

“…Neurotransmitters, essential in mammalian pain modulation, have also been identified in the Iberian wall lizard ( De la Iglesia et al., 1994 ). Additionally, cyclooxygenase (COX) enzyme expression of ball pythons, eastern box turtles and yellow-belly geckos have been studied ( Buch et al., 2018 ; Buch et al., 2017 ; Royal et al., 2012 ; Sadler et al., 2016 ). Mu- and delta-opioid receptors have also been identified in turtles ( Xia & Haddad, 2001 ), and mu-opioid receptors in ball pythons ( Kharbush et al., 2017 ).…”

Pharmacokinetics of ketorolac in juvenile loggerhead sea turtles (Caretta caretta) after a single intramuscular injection

“…To the authors’ knowledge, the current information about ketorolac in turtles is limited to one published eastern box turtle study, one abstract on eastern box turtles and yellow‐bellied sliders, and two loggerhead case reports (Cerreta et al, 2019; Henson & Lewbart, 1998; Jaeger et al, 2003; Lewbart et al, 2001). As a nonselective cyclooxygenase (COX) inhibitor, ketorolac may provide broader analgesic coverage in reptiles than more selective COX inhibitors such as meloxicam, based on the variable increase in expression of both COX‐1 and COX‐2 receptors following trauma in reptiles (Perry & Nevarez, 2018; Royal et al, 2012; Sadler et al, 2016).…”

Ketoprofen pharmacokinetics of R‐ and S‐isomers in juvenile loggerhead sea turtles (Caretta caretta) after single intravenous and single‐ and multidose intramuscular administration

“…Previous pharmacokinetic studies in loggerhead turtles ( Caretta caretta ) evaluating meloxicam, a COX‐2 selective NSAID, at 0.1 mg/kg IM and IV and 0.2 mg/kg IV, found low plasma concentrations with more rapid elimination than in mammals; therefore, the authors did not recommend meloxicam at those doses for sea turtles (Claus et al., ; Lai et al., ). Studies of COX‐1 and COX‐2 expression in eastern box turtles ( Terrapene carolina carolina ) (Royal, Lascelles, Lewbart, Correa, & Jones, ) and ball pythons ( Python regius ) (Sadler et al., ) suggest the possibility that a nonselective NSAID with both COX‐1 and COX‐2 activity, such as ketoprofen, may be more efficacious in controlling pain and inflammation in chelonians than a COX‐2 selective drug. Ketoprofen also has the advantage in the United States and some other countries of having a commercially available veterinary formulation for injection at a concentration convenient for larger turtles (Ketofen®, 100 mg/ml solution).…”