Protective Effect of Ebselen on Ischemia-reperfusion Injury in Epigastric Skin Flaps in Rats

Abstract

The purpose of this study was to determine the role of oxidized diacylglycerol (DAG) and the molecular mechanism underlying ischemia-reperfusion (I/R) injury in rat skin flaps. The protective effect of ebselen on the viability of rat skin flaps with I/R injury was investigated. Flaps were designed and raised in the left inguinal region. Then, a microvascular clamp was applied to the vascular pedicle and reperfused after 6 hr. After 7 days of I/R (I/R group), the skin flap survival area ratio was significantly reduced compared to the normal skin. The administration of ebselen significantly improved the ratio compared to the I/R group. The flap survival area ratio of the I/R + ebselen group was significantly improved compared to the I/R + vehicle group. In the I/R + ebselen group, the oxidized DAG content and intensity of phosphorylated PKCα and PKCδ were significantly lower compared to the I/R + vehicle group. Furthermore, the inflammatory response was suppressed in the I/R + ebselen group compared to the I/R + vehicle group. These results indicate that ebselen is useful as a preventive and therapeutic agent for skin flap necrosis caused by I/R, because of reduction and elimination of oxidized DAG.

Protective effects of the bioactive peptide from maggots against skin flap ischemia‒reperfusion injury in rats

“…Inflammatory cytokines can enhance macrophages, causing validated cascades and aggravated tissue injury [ 54 ]. As shown in other studies, oxidants, such as ROS and lipid peroxides, are involved in flap graft reconstruction operations, thus leading to I/R injury [ 55 ]. Our findings indicated that rats experiencing skin flap I/R presented elevated TNF-α and IL-6 expression, and BPM intake markedly downregulated these proinflammatory factors.…”

Selenization of Small Molecule Drugs: A New Player on the Board

“…It should also be highlighted that Ebselen, a selenenylamide molecule, has been highly investigated throughout the years due to its GPx-mimicking activity and its antioxidant and electrophilic properties. Of note, a vast variety of clinical trials have been carried out to determine the therapeutic potential of this selenocompound in different pathological conditions such as Meinere’s disease, hypo/mania, and noise-induced hearing loss. − Besides, a great number of studies have reported the potential application of this experimental drug against bacterial, viral, and fungal infections, ,− cancer cells, − ischemia–reperfusion (I/R) injury, , tobramycin-induced ototoxicity, osteoarthritis, and Azheimer’s disease. − Importantly, a growing body of compelling studies has shown that Ebselen can be a promising candidate for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as it has proven to be an effective inhibitor of its main protease (M pro ), which is pivotal for the life cycle of this virus, by forming a selenosulfide bond with the thiol group of the catalytic cysteine (Cys) 145. Additionally, this experimental drug exhibited great anti-SARS-CoV-2 activity in infected Vero cells.…”