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

Oxidative stress may contribute to lymphedema and subsequent tissue damage. However, the causal role of oxidative stress in lymphedema remains unclear.

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.

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 (2 mg/kg), baicalein (15 mg/kg), MK-886 (3 mg/kg), zileuton (6.25 mg/kg), diphenyleneiodonium (DPI; 1 mg/kg), sulforaphane (30 mg/kg), oryzanol (30 mg/kg) or sesamol (30 mg/kg) once daily for 14 d from the day of operation. All animals were sacrificed on day 14.

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.

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.