Effects of diammonium glycyrrhizinate on random skin flap survival in rats: An experimental study

Lv,Qing‑Bo; Gao,Xiang; Lin,Ding‑Sheng; Chen,Yun; Cao,Bin; Zhou,Kai‑Liang

doi:10.3892/br.2016.733

Effects of diammonium glycyrrhizinate on random skin flap survival in rats: An experimental study

Authors:
- Qing‑Bo Lv
- Xiang Gao
- Ding‑Sheng Lin
- Yun Chen
- Bin Cao
- Kai‑Liang Zhou
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Affiliations: Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China
Published online on: August 2, 2016 https://doi.org/10.3892/br.2016.733
Pages: 383-389

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Abstract

Partial necrosis of skin flaps continues to restrict the survival of local skin flaps following plastic and reconstructive surgeries. The aim of the present study was to investigate the effects of diammonium glycyrrhizinate (DG), a salt of glycyrrhetinic acid that has been widely used in the therapy of chronic hepatitis and human immunodeficiency virus infection, on random skin flap survival in rats. McFarlane flaps were established in 60 male Sprague‑Dawley rats randomly divided into three groups. Group I served as the control group and was injected with saline (10 mg/kg) once per day. Group II and group III were the experimental groups, and were injected with 10 mg/kg DG once and twice per day, respectively. On day 7, the survival area of the flap was measured. Tissue samples were stained with hematoxylin and eosin and immunohistochemically evaluated. Tissue edema, neutrophil density, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were evaluated. The mean survival areas of the flaps of group II were significantly larger when compared with those of group I (P<0.05), and the rats of group III exhibited significantly higher survival areas than group II (P<0.05). Histologic and immunohistochemical evaluation showed that microvessel development and the expression level of vascular endothelial growth factor were higher in the two experimental groups than in the control group. Furthermore, SOD activity was significantly increased (P<0.05), while the neutrophil density and MDA level were significantly reduced (P<0.05) in group II when compared with group I. Significant differences between group II and group III with regard to SOD activity and MDA level were also observed (P<0.05). Thus, DG may have a dose‑dependent effect on promoting the survival of random skin flaps.

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1	Yang M, Sheng L, Li H, Weng R and Li QF: Improvement of the skin flap survival with the bone marrow-derived mononuclear cells transplantation in a rat model. Microsurgery. 30:275–281. 2010.PubMed/NCBI
2	Kim HJ, Xu L, Chang KC, Shin SC, Chung JI, Kang D, Kim SH, Hur JA, Choi TH, Kim S, et al: Anti-inflammatory effects of anthocyanins from black soybean seed coat on the keratinocytes and ischemia-reperfusion injury in rat skin flaps. Microsurgery. 32:563–570. 2012. View Article : Google Scholar : PubMed/NCBI
3	Bin C, Dingsheng L, Leyi C, Bin L, Yuting L, Liren W and Zhijie L: Beneficial effects of Xuebijing injection on random skin flap survival in rats. J Surg Res. 196:421–426. 2015. View Article : Google Scholar : PubMed/NCBI
4	Cao B, Wang L, Lin D, Cai L and Gao W: Effects of lidocaine on random skin flap survival in rats. Dermatol Surg. 41:53–58. 2015. View Article : Google Scholar : PubMed/NCBI
5	vanRossum TG, Vulto AG, de Man RA, Brouwer JT and Schalm SW: Review article: Glycyrrhizin as a potential treatment for chronic hepatitis C. Aliment Pharmacol Ther. 12:199–205. 1998. View Article : Google Scholar : PubMed/NCBI
6	Iino S, Tango T, Matsushima T, Toda G, Miyake K, Hino K, Kumada H, Yasuda K, Kuroki T, Hirayama C, et al: Therapeutic effects of stronger neo-minophagen C at different doses on chronic hepatitis and liver cirrhosis. Hepatol Res. 19:31–40. 2001. View Article : Google Scholar : PubMed/NCBI
7	Yuan H, Ji WS, Wu KX, Jiao JX, Sun LH and Feng YT: Anti-inflammatory effect of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis. World J Gastroenterol. 12:4578–4581. 2006. View Article : Google Scholar : PubMed/NCBI
8	Hou SZ, Li Y, Zhu XL, Wang ZY, Wang X and Xu Y: Ameliorative effects of diammonium glycyrrhizinate on inflammation in focal cerebral ischemic-reperfusion injury. Brain Res. 1447:20–27. 2012. View Article : Google Scholar : PubMed/NCBI
9	Mandriota SJ, Pyke C, Di Sanza C, Quinodoz P, Pittet B and Pepper MS: Hypoxia-inducible angiopoietin-2 expression is mimicked by iodonium compounds and occurs in the rat brain and skin in response to systemic hypoxia and tissue ischemia. Am J Pathol. 156:2077–2089. 2000. View Article : Google Scholar : PubMed/NCBI
10	Kelly CP, Gupta A, Keskin M and Jackson IT: A new design of a dorsal flap in the rat to study skin necrosis and its prevention. J Plast Reconstr Aesthet Surg. 63:1553–1556. 2010. View Article : Google Scholar : PubMed/NCBI
11	Ren H, Lin D, Mou Z and Dong P: The adverse effect of selective cyclooxygenase-2 inhibitor on random skin flap survival in rats. PLoS One. 8:e828022013. View Article : Google Scholar : PubMed/NCBI
12	Chen Y, Tong H, Zhang X, Tang L, Pan Z, Liu Z, Duan P and Su L: Xuebijing injection alleviates liver injury by inhibiting secretory function of Kupffer cells in heat stroke rats. J Tradit Chin Med. 33:243–249. 2013. View Article : Google Scholar : PubMed/NCBI
13	Yamaguchi S, Watanabe G, Tomita S and Tabata S: Lidocaine-magnesium blood cardioplegia was equivalent to potassium blood cardioplegia in left ventricular function of canine heart. Interact Cardiovasc Thorac Surg. 6:172–176. 2007. View Article : Google Scholar : PubMed/NCBI
14	Liu L, Liu Y, Cui J, Liu H, Liu YB, Qiao WL, Sun H and Yan CD: Oxidative stress induces gastric submucosal arteriolar dysfunction in the elderly. World J Gastroenterol. 19:9439–9446. 2013. View Article : Google Scholar : PubMed/NCBI
15	Coskunfirat OK, Cinpolat A, Bektas G, Ogan O and Taner T: Comparing different postconditioning cycles after ischemia reperfusion injury in the rat skin flap. Ann Plast Surg. 72:104–107. 2014. View Article : Google Scholar : PubMed/NCBI
16	Xu R, Ge J, Lei Y and Lu X: Improvement effect of estrogen on flap reperfusion injury and blood supply. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 23:964–968. 2009.(In Chinese). PubMed/NCBI
17	Zhang F and Lineaweaver W: Acute and sustained effects of vascular endothelial growth factor on survival of flaps and skin grafts. Ann Plast Surg. 66:581–582. 2011. View Article : Google Scholar : PubMed/NCBI
18	Zhang F, Fischer K, KomorowskaTimek E, Guo M, Cui D, DorsettMartin W, Buncke HJ and Lineaweaver WC: Improvement of skin paddle survival by application of vascular endothelial growth factor in a rat TRAM flap model. Ann Plast Surg. 46:314–319. 2001. View Article : Google Scholar : PubMed/NCBI
19	Cai L, Cao B and Lin D: Effects of Traditional Chinese Medicine Huangqi Injection (Radix astragali) on Random Skin Flap Survival in Rats. J Reconstr Microsurg. 31:565–570. 2015. View Article : Google Scholar : PubMed/NCBI
20	Cai L, Huang W and Lin D: Effects of traditional Chinese medicine Shuxuetong injection on random skin flap survival in rats. Sci World J. 2014:8165452014. View Article : Google Scholar
21	Tang B, Qiao H, Meng F and Sun X: Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats. Braz J Med Biol Res. 40:1637–1646. 2007. View Article : Google Scholar : PubMed/NCBI
22	Abe K, Ikeda T, Wake K, Sato T, Sato T and Inoue H: Glycyrrhizin prevents of lipopolysaccharide/D-galactosamine-induced liver injury through down-regulation of matrix metalloproteinase-9 in mice. J Pharm Pharmacol. 60:91–97. 2008. View Article : Google Scholar : PubMed/NCBI
23	Tsuruoka N, Abe K, Wake K, Takata M, Hatta A, Sato T and Inoue H: Hepatic protection by glycyrrhizin and inhibition of iNOS expression in concanavalin A-induced liver injury in mice. Inflamm Res. 58:593–599. 2009. View Article : Google Scholar : PubMed/NCBI
24	Yoshida T, Abe K, Ikeda T, Matsushita T, Wake K, Sato T, Sato T and Inoue H: Inhibitory effect of glycyrrhizin on lipopolysaccharide and d-galactosamine-induced mouse liver injury. Eur J Pharmacol. 576:136–142. 2007. View Article : Google Scholar : PubMed/NCBI
25	Lee CH, Park SW, Kim YS, Kang SS, Kim JA, Lee SH and Lee SM: Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biol Pharm Bull. 30:1898–1904. 2007. View Article : Google Scholar : PubMed/NCBI
26	Yingxin G, Guoqian Y, Jiaquan L and Han X: Effects of natural and recombinant hirudin on VEGF expression and random skin flap survival in a venous congested rat model. Int Surg. 98:82–87. 2013. View Article : Google Scholar : PubMed/NCBI
27	Bächle AC, Mörsdorf P, Rezaeian F, Ong MF, Harder Y and Menger MD: N-acetylcysteine attenuates leukocytic inflammation and microvascular perfusion failure in critically ischemic random pattern flaps. Microvasc Res. 82:28–34. 2011. View Article : Google Scholar : PubMed/NCBI
28	Neurath MF, Fuss I, Schürmann G, Pettersson S, Arnold K, Müller-Lobeck H, Strober W, Herfarth C and Büschenfelde KH: Cytokine gene transcription by NF-kappa B family members in patients with inflammatory bowel disease. Ann N Y Acad Sci. 859:(1 INTESTINAL PL). 149–159. 1998. View Article : Google Scholar : PubMed/NCBI
29	Blackwell TS and Christman JW: The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol. 17:3–9. 1997. View Article : Google Scholar : PubMed/NCBI
30	Vourtsis SA, Spyriounis PK, Agrogiannis G, Papalois A and Ionac M: Does VEGF have an effect on the survival of a long random skin flap by its application at the recipient area? Chirurgia (Bucur). 107:494–500. 2012.PubMed/NCBI
31	Fang T, Lineaweaver WC, Chen MB, Kisner C and Zhang F: Effects of vascular endothelial growth factor on survival of surgical flaps: A review of experimental studies. J Reconstr Microsurg. 30:1–13. 2014. View Article : Google Scholar : PubMed/NCBI
32	Braunersreuther V and Jaquet V: Reactive oxygen species in myocardial reperfusion injury: From physiopathology to therapeutic approaches. Curr Pharm Biotechnol. 13:97–114. 2012. View Article : Google Scholar : PubMed/NCBI
33	Ozkan F, Senayli Y, Ozyurt H, Erkorkmaz U and Bostan B: Antioxidant effects of propofol on tourniquet-induced ischemia-reperfusion injury: An experimental study. J Surg Res. 176:601–607. 2012. View Article : Google Scholar : PubMed/NCBI
34	Cui J, Liu L, Zou J, Qiao W, Liu H, Qi Y and Yan C: Protective effect of endogenous hydrogen sulfide against oxidative stress in gastric ischemia-reperfusion injury. Exp Ther Med. 5:689–694. 2013.PubMed/NCBI
35	Sirota TV, Zakharchenko MV and Kondrashova MN: Cytoplasmic superoxide dismutase activity is a sensitive indicator of the antioxidant status of the rat liver and brain. Biomed Khim. 60:63–71. 2014.(In Russian). View Article : Google Scholar : PubMed/NCBI
36	Sun L, Li Y, Shi J and Wang X and Wang X: Protective effects of ligustrazine on ischemia-reperfusion injury in rat kidneys. Microsurgery. 22:343–346. 2002. View Article : Google Scholar : PubMed/NCBI