The Effect of Coenzyme Q 10 (Ubiquinone) on Random Pattern Skin Flap Survival in Rat Model Aslı Can, MD,* Metin Temel, MD,† Recep Dokuyucu, MD,‡ and Mehmet Mutaf, MD§ Background: In this study, the effect of coenzyme Q 10 (CQ 10 ) on flap survival was investigated. Methods: Fifty Wistar Albino rats were divided into 5 groups. The survival rates of the skin flaps were assessed 10 days after complete elevation of the flaps. Re- gions of survival and necrosis were drawn on transparent acetate sheets and scanned into a computer. Tissue samples were assessed histopathologically after staining with hematoxylin-eosin, vascular endothelial growth factor staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-Biotin Nick End-labeling staining. To evaluate the antioxidant effect of CQ 10 ; malon- dialdehyde, nitric oxide levels were measured. Results: Viable flaps area was found higher in groups 3 and 4 as compared to groups 1, 2, and 5. In terms of vascular proliferation, elevated angiogenesis was observed in pathological specimens of groups 3 and 4 as compared to groups 1, 2, and 5. Malondialdehyde levels in groups 3 and 4 were found to be signifi- cantly decreased as compared to groups 1, 2 and 5 (P < 0.05). Moreover, serum levels of CQ 10 were found significantly increased in groups 3 and 4 (P < 0.05). Conclusions: In conclusion, CQ 10 significantly improves flap viability in rat model, and the highest levels of serum CQ 10 can be obtained by oral administration. Key Words: coenzyme Q 10 , ubiquinone, flap survival, antioxidant effect, angiogenesis, apoptosis (Ann Plast Surg 2015;00: 00–00) R andom pattern skin flaps are frequently used for the repair of tissue defects. Length-to-width ratio of the random flaps is limited. 1–3 As the length of the flap increases, survival of the flaps decrease, and this eventually results in distal flap necrosis and tissue loss. 4 To enhance sur- vival rate of flaps, studies focused on antioxidants, which increase the flap survival 5,6 and inhibit apoptosis. 7 Coenzyme Q 10 (CQ 10 ) has been shown to neutralize the effects of free radicals, especially the superoxide radicals, after ischemia reperfusion. 8 Coenzyme Q 10 can directly interact with the free radicals or it can induce the production of other antioxidants by reducing tocopherol and ascorbate, thus showing antioxidant effect and inhibiting mem- brane lipid peroxidation. The role of CQ 10 in the flap survival has not been assessed yet. In the present study, we aimed to investigate the ef- fect of CQ 10 on flap survival in a classic model of random pattern rat dorsal flap. We compared the results of oral, parenteral, and local ad- ministrations of CQ 10 to determine the most useful application. MATERIALS AND METHOD Approval for this study was taken from Local Ethics Committee. The study was held by using total of 50 healthy, adult, and male Wistar Albino rats 105 to 120 days old, 250 to 350 g in weight. Subjects were randomly divided into 5 groups as each group received 10 subjects. Rats were anesthetized by 30 mg/kg intramuscular ketamine hy- drochloride and 10 mg/kg xylazine hydroklorid. After anesthesia appli- cation, 4 Â 10 cm (ie, 1:2.5 ratio) axial flaps were raised by dissecting the areolar tissue at the level of the panniculus carnosus and deep fascia of the rats’ dorsal musculatures by the method of “Mcfarlane flap. ” 9 Then, the flap was repositioned in its original position and was sutured with 4–0 monofilament nylon single stitches at 0.5-cm intervals (Figure 1). The dressings and wound care of rats were made carefully by daily cleaning with povidone-iodine. For the prophylaxis of infection, 150 mg/kg of sin- gle dose subcutaneous Ampicillin was administered to all groups. Experimental groups were generated as follows: Group 1 (control group): only wound care was done and no addi- tional application was held. Group 2 (stress group): after standard wound care, daily intraperito- neally 1 mL of physiological saline was administered to mimic stress. Group 3 (intraperitoneal): 1 mL 10 mg/kg CQ 10 solution was applied intraperitoneally by 27 gauge syringe once per day after wound care and 1 hour before surgery. Group 4 (gavage): starting 3 hours before surgery, capsule form of CQ 10 was dissolved in preheated physiological saline and adminis- tered as 150 mg/kg per day by 24 G branul (Mediflo) (by gavage) once per day. Group 5 (local): starting 4 hours before surgery, after standard wound care with the help of cotton swabs, liquid form of CQ 10 was mixed with olive oil, 1:1 ratio and drops containing CQ 10 (100 mg) were ap- plied to the entire surface of the flap. At the 10th day of the experiment, rats were prepared for surgical operation and anesthetized by the same method and 0.5 Â 0.5 cm of tis- sue samples were taken from distal, middle, and proximal one third por- tions of dorsal flap regions. Also, intracardiac 5 mL blood samples were taken, and the experiment was terminated. Serum of the blood samples were separated by centrifuging at 5000 rpm for 5 minutes and subjected to biochemical analysis. To evaluate tissue malondialdehyde (MDA) and nitric oxide (NO) levels, 1 Â 1 cm of tissue samples were taken from the middle portion of the dorsum of subjected to biochemical analysis. Clinical Evaluation In clinical evaluations, the survival rates of the skin flaps were assessed 10 days after complete elevation of the flaps. Regions of sur- vival and necrosis were drawn on transparent acetate sheets and scanned into the computer. Regions of survival and necrosis were dyed in different colors, and survival rates were assessed by planimetric anal- ysis as follows: Flap survival rate ¼ Area of survival ð Þ% Total flap area ð Þ ð ÞÂ 100 Histomorphological Examination Tissue samples were fixed in 10% formalin and embedded in paraffin blocks. Four-micron sections were obtained by microtome. Sections were stained by the methods of hematoxylin-eosin, vascular endothelial growth factor (VEGF) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNNEL) and examined under light microscope. In histopathologi- cal evaluations of tissue samples, parameters of polymorphonuclear Received November 7, 2014, and accepted for publication, after revision January 29, 2015. From the *Private Gözde Hospital, İzmir; †Department of Plastic and Reconstructive Surgery, ‡Department of Physiology, Mustafa Kemal University, School of Med- icine, Hatay; and §Department of Plastic and Reconstructive Surgery, Gaziantep University School of Medicine, Gaziantep, Turkey. Conflicts of interest and sources of funding: none declared. Reprints: Metin Temel, MD, Department of Plastic and Reconstructive Surgery, Mustafa Kemal University, School of Medicine, Hatay, Turkey. E-mail: drmetintemel@hotmail.com. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/15/0000–0000 DOI: 10.1097/SAP.0000000000000504 RESEARCH Annals of Plastic Surgery • Volume 00, Number 00, Month 2015 www.annalsplasticsurgery.com 1 Copyright © 2015 Wolters Kluwer Health, Inc. 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