Effects of NecroX-5 on the Survival of a Random Pattern Skin Flap in Mice

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. IMAGES Images Random skin flaps have been widely used for loss of skin and subcutaneous tissues for thousands of years [1]. Unlike the axial pattern flap, the blood supply of a random pattern flap is based on small unnamed vessels. Most unnamed vessels are part of the subdermal plexus [2]. Partial or complete skin flap necrosis is a common problem encountered postoperatively. Flap necrosis caused by disruption of blood supply within the flap often occurs after the surgery, and requires a secondary operation [1,2]. Researchers have focused on enhancing flap viability to avoid potential necrosis of the flaps [1-3]. Various pharmacological and surgical delay procedures may be used for enhancement of skin flap viability [3]. NecroX, a member of a novel class of small molecule necrosis/necroptosis inhibitors, inhibits receptor-interacting protein (RIP) kinase-induced necroptosis and is a mitochondrial reactive oxygen species (ROS) scavenger [4,5]. It has exhibited cytoprotective activity against various insults [4,5]. NecroX-5 is a derivative of the NecroX series compounds, with chemical composition C25H31N3O3S.2CH4O3S and molecular weight 453.61 (Fig. 1) [4]. Therapeutic effects of NecroX-5 in ischemia and reperfusion injury of the canine liver and murine heart models have been evaluated [4]. Despite its anti-necrotic effects, no studies on the effect of NecroX compounds on the survival of the skin flap have been reported. The purpose of this experimental study is performing topographical evaluation of the effect of NecroX-5 on the viability of random pattern dorsal skin flaps in mice. All animal experiments were conducted according to the guidelines for animal experimentation of the author's institution and with their approval. Thirty BALB/c mice (female, 8-week-old, 16.63 ± 0.32 g body weight) were used. They were distributed randomly into three equal groups with 10 mice each. Group I received daily intraperitoneal administration of 10 mg/kg NecroX-5 (LG Life Sciences) in distilled water from 1 day before surgery until 7 days postoperatively, while group II received NecroX-5 at a higher concentration (30 mg/kg in distilled water). Mice in the control group were administered the same amount of distilled water instead of NecroX-5, with a volume of approximately 0.2 ± 0.013 mL. A cranially based random pattern skin flap measuring 1.0 cm × 3.0 cm was elevated under the panniculus carnosus layer on the dorsum of each mouse. They were anesthetized intramuscularly with a …