The role of cyclooxygenase-derived oxidative stress in surgically induced lymphedema in a mouse tail model

Ting Chen Chang, Yih Huei Uen, Cheng Hung Chou, Joen Rong Sheu, Duen Suey Chou

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Context: Oxidative stress may contribute to lymphedema and subsequent tissue damage. However, the causal role of oxidative stress in lymphedema remains unclear. Objective: We attempted to detect and identify the free radicals formed in lymphedema fluid and assessed the protective mechanisms and effects of specific enzyme inhibitors and natural antioxidants. Materials and methods: To study the level of postsurgical oxidative stress with lymphedema in a mouse tail model, we used an electron spin resonance (ESR) method and an ascorbyl radical's ESR spectrum as an oxidative stress biomarker. The drug-treatment group received an i.p. injection with indomethacin (2mg/kg), baicalein (15mg/kg), MK-886 (3mg/kg), zileuton (6.25mg/kg), diphenyleneiodonium (DPI; 1mg/kg), sulforaphane (30mg/kg), oryzanol (30mg/kg) or sesamol (30mg/kg) once daily for 14d from the day of operation. All animals were sacrificed on day 14. Results: Administration of indomethacin, sulforaphane, oryzanol and sesamol significantly suppressed both the tail volume (56.9%, 77.8%, 72.2% and 38.1% inhibition, respectively, p<0.01) and ascorbyl radical signals (31.4%, 54.5%, 79.3% and 57.1% inhibition, respectively, p<0.01), compared with the control mice. No significant differences were found between any of the baicalein, MK-886, or zileuton groups compared with the control. DPI suppressed the tail volume (25.9% inhibition, p<0.01) but not the ascorbyl radical signals. Conclusion: This study showed that COX-derived oxidative stress plays a major role in the pathological mechanisms of surgically induced lymphedema. Indomethacin, sulforaphane, oryzanol and sesamol exhibit potent protective properties against surgically induced lymphedema.

Original languageEnglish
Pages (from-to)573-580
Number of pages8
JournalPharmaceutical Biology
Volume51
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Ascorbyl radical
  • Electron spin resonance
  • Indomethacin
  • Oryzanol
  • Sesamol
  • Sulforaphane

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Complementary and alternative medicine
  • Pharmacology
  • Pharmaceutical Science

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