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

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 (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. 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, p50.01) and ascorbyl radical signals (31.4%, 54.5%, 79.3% and 57.1% inhibition, respectively, p50.01), 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, p50.01) 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.

Mechanisms of Ascorbyl Radical Formation in Human Platelet-Rich Plasma

“…We recently applied ESR spectroscopy in detecting Asc ∙ to investigate the oxidative status of lymphedema, suggesting that COX-derived oxidative stress plays a major role in the pathological mechanisms of surgically induced lymphedema [10]. However, in the current study, COX-derived oxidative stress played only a minor role in oxidative stress in human PRP.…”

“…Asc ∙ has been detected by ESR in various biological samples including plasma, serum, whole blood, cerebrospinal fluid, skin, extracellular fluid, synovial fluid, gastric mucosa, seminal fluid, tumors, heart tissue, and others [7]. We recently applied ESR spectroscopy in detecting the Asc ∙ to investigate the mechanisms of oxidative stress caused by lymphedema in mice [10]. In this study, we used upstream substances, enzyme inhibitors, and free radical scavengers to delineate the mechanisms of Asc ∙ formation in human platelet-rich plasma (PRP).…”

S1 Guidelines – Dermatoses associated with dermal lymphostasis

“…This accelerates the xanthine oxidoreductase‐dependent formation of reactive oxygen species (ROS) caused by increased purine degradation during times of local hypoxia and reperfusion with critical tissue oxygen levels. Together with increased lipid degradation in the context of lipid peroxidation, said processes result in massive oxidative stress, which promotes secondary tissue remodeling .…”

S1‐Leitlinie – Dermatosen bei dermaler Lymphostase

“…Zudem überwiegen zunehmend pro‐oxidative Stoffwechselprozesse, die durch einen vermehrten Purinabbau bei regionalen Hypoxie‐ und Reperfusionsphasen mit kritischen Sauerstoffwerten im Gewebe über die Xanthinoxidoreduktase zu der beschleunigten Bildung von reaktiven Sauerstoffspezies (ROS) führen. Gemeinsam mit der gesteigerten Degradation von Lipiden im Rahmen der Lipidperoxidation resultiert ein enormer oxidativer Stress, der den sekundären Gewebeumbau begünstigt .…”