• 1. Read MR. Evaluation of the use of anesthesia and analgesia in reptiles. J Am Vet Med Assoc 2004; 224: 547552.

  • 2. Olesen MG, Bertelsen MF, Perry SF, et al. Effects of preoperative administration of butorphanol or meloxicam on physiologic responses to surgery in ball pythons. J Am Vet Med Assoc 2008; 233: 18831888.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Vane JR, Botting RM. Mechanism of action of nonsteroidal antiinflammatory drugs. Am J Med 1998; 104: 2S8S.

  • 4. Eberhart CE, Coffey RJ, Radhika A, et al. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994; 107: 11831188.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Dannenberg AJ, Lippman SM, Mann JR, et al. Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets for chemoprevention. J Clin Oncol 2005; 23: 254266.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three AKTs. Genes Dev 1999; 13: 29052927.

  • 7. Doddareddy MR, Rawling T, Ammit AJ. Targeting mitogen-activated protein kinase phosphatase-1 (MKP-1): structure-based design of MKP-1 inhibitors and upregulators. Curr Med Chem 2012; 19: 163173.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Laveti D, Kumar M, Hemalatha R, et al. Anti-inflammatory treatments for chronic diseases: a review. Inflamm Allergy Drug Targets 2013; 12: 349361.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Marnett LJ. The COXIB experience: a look in the rearview mirror. Annu Rev Pharmacol Toxicol 2009; 49: 265290.

  • 10. Duncan A. Reptile and amphibian analgesia. In: Miller RE, Fowler M, eds. Fowler's zoo and wild animal medicine. St Louis: WB Saunders, 2012: 247253.

    • Search Google Scholar
    • Export Citation
  • 11. Sladky KK, Mans C. Clinical analgesia in reptiles. J Exot Pet Med 2012; 21: 158167.

  • 12. Reed DW, Bradshaw WS, Xie W, et al. In vivo and in vitro expression of a non-mammalian cyclooxygenase-1. Prostaglandins 1996; 52: 269284.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Seebacher F, Franklin CE. Prostaglandins are important in thermoregulation of a reptile ( Pogona vitticeps). Proc R Soc Lond B Biol Sci 2003; 270: S50S53.

    • Search Google Scholar
    • Export Citation
  • 14. Royal LW, Lascelles BDX, Lewbart GA, et al. Evaluation of cyclooxygenase protein expression in traumatized versus normal tissues from eastern box turtles ( Terrapene carolina carolina). J Zoo Wildl Med 2012; 43: 289295.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Smith DA, Barker IK. Healing of cutaneous wounds in the common garter snake ( Thamnophis sirtalis). Can J Vet Res 1988; 52: 111119.

    • Search Google Scholar
    • Export Citation
  • 16. National Research Council. Guide for the care and use of laboratory animals. Washington, DC: National Academies Press, 2011;4149.

  • 17. Hodshon RT, Sura PA, Schumacher JP, et al. Comparison of firstintention healing of carbon dioxide laser, 4.0-MHz radiosurgery, and scalpel incisions in ball pythons (Python regius). Am J Vet Res 2013; 74: 499508.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Cekanova M, Uddin MJ, Bartges JW, et al. Molecular imaging of cyclooxygenase-2 in canine transitional cell carcinomas in vitro and in vivo. Cancer Prev Res (Phila Pa) 2013; 6: 466476.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Cekanova M, Uddin MJ, Legendre AM, et al. Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model. J Biomed Opt 2012; 17: 116002.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Rathore K, Cekanova M. Animal model of naturally occurring bladder cancer: characterization of four new canine transitional cell carcinoma cell lines. BMC Cancer 2014; 14: 465.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Tuttle AD, Papich M, Lewbart GA, et al. Pharmacokinetics of ketoprofen in the green iguana (Iguana iguana) following single intravenous and intramuscular injections. J Zoo Wildl Med 2006; 37: 567570.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Divers SJ, Papich M, McBride M, et al. Pharmacokinetics of meloxicam following intravenous and oral administration in green iguanas ( Iguana iguana). Am J Vet Res 2010; 71: 12771283.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement

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

View More View Less
  • 1 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 2 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 3 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 4 Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 5 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 6 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 7 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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.

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.

Contributor Notes

Address correspondence to Dr. Cekanova (mcekanov@utk.edu).