Comparison of the Effects of Alpha Lipoic Acid and Vitamin C on Colonic Anastomosis in the Rat Sepsis Model

Abstract

Certain conditions, mainly peritoneal contamination, are considered to be risky for anastomosis. In our study, the effect of vitamin C and lipoic acid combination on anastomosis healing following colonic anastomosis performed in rats with experimentally-induced intraabdominal sepsis has been investigated. A total of 48 male Sprague Dawley albino rats weighing between 200-250 gram were included in the study and allocated to 6 groups with 8 rats in each. The rats in the control group were given only routine enteral feed in the preoperative and postoperative periods. The rats in the vitamin C group were given 100 mg/kg vitamin C IV/S.C, the rats in the lipoic acid group were given 50 mg/kg lipoic acid daily via the peroral route, and the rats in the vitamin C + lipoic acid group were given vitamin C and lipoic acid via the same routes beginning from the operation day. Perforation was induced in the sigmoid colon and intraabdominal sepsis was induced, and this perforation site was resected 24 hours later and an end-to-end colonic anastomosis was performed. The anastomosis site was taken out of the abdomen and the bursting pressure was measured. Biochemical analysis was performed for this site in order to analyze the prolidase enzyme, hydroxyproline and malondialdehyde thereafter. While the mean bursting pressures and hydroxyproline levels of the combination group were found to be statistically significantly higher than those of the other study groups (p

Keywords

• Rat, intraabdominal sepsis, anastomosis, vitamin C, lipoic acid

Comparison of the Effects of Alpha Lipoic Acid and Vitamin C on Colonic Anastomosis in the Rat Sepsis Model

Öz

Periton kontaminasyonun anastomoz için risk olarak kabul edilir. Bizim çalışmamızda, deneysel kaynaklı karın içi sepsis ile sıçanlarda yapılan kolon anastomoz iyileşmesi üzerine C vitamini ve lipoik asit kombinasyonunun etkisi araştırılmıştır.Kontrol grubundaki sıçanlar preoperatif ve postoperatif dönemde sadece rutin enteral besleme verildi.C vitamini grubundaki fareler, 100 mg/kg vit C IV/SC verildi, lipoik asit grubunda farelere oral yoldan her gün 50 mg/kg alfa lipoik asit verildi ve C vitamini+lipoik asit alan grupta farelere operasyon gününden itibaren aynı yol ile C vitamini ve lipoik asit verildi. Perforasyon sigmoid kolonda oluşturularak karın içi sepsis meydanagetirildi. Bu perforasyon sitesi 24 saat sonra rezeke edildi ve uç uca kolon anastomoz yapıldı. Anastomoz yeri karın dışına alındı ve patlama basıncı ölçüldü. Biyokimyasal olarak prolidaz enzimi, hidroksiprolin ve malondialdehit bu site için analiz edildi. Kombinasyon grubunda patlama basıncı ve hidroksiprolin düzeyleri diğer gruplardan istatistiksel olarak anlamlı derecede yüksekti (p <0,001). Prolidaz ve malondialdehit düzeyleri kombinasyon grubunda diğer gruplarına göre istatiksel olarak dfüşük bulundu. Antioksidan olarak vit C ve lipoik asidin kombine kullanımı dah iyi anastomoz iyileşmesi ve gerginlik sağlamaktadır

Anahtar Kelimeler

• Rat, karın içi sepsis, anastomaz, vit C, lipoik asit

Kaynakça

1. Tasdelen A, Algin C, Ates E, Kiper H, Inal M, Sahin F. Effect of leptin on healing ofcolonic anastomoses in rats. Hepatogastroenterology 2004; 51:994-7.
2. Zeng YX, Chen L, Tao S F, Song P, Xu SM. Diagnosis and management of colonic injuries following blunt trauma. World J Gastroenterol 2007; 13:633-6.
3. Head KA. Ascorbic acid in the prevention and treatment of cancer. Altern Med Rev 1998; 3:174-86.
4. Rojkind M, Gatmaitan Z. Connective tissue biomatrix in rat hepatocytes. J Cell Biol 1980; 87:55-256.
5. Bao Y, Li YS, Li JS. A laboratory model of intraabdominal infections by fistula. Chin J Exp Surg 2004; 21: 99.
6. Vazquez-Ortiz FA, Moron-Fuenmayor OE, Gonzalez- Mendez NF. Hydroxyproline Measurement by HPLC: Improved Method of Total Collagen Determination in Meat Samples. J Liquid Chromatogr Related Tech 2004;27: 2771–80.
7. Myara I, Charpentier C, Lemonnier A. Optimal conditions for prolidase assay by proline colorimetric determina- tion: application to imidodipeptiduria. Clin Chim Acta 1982; 125: 193–205.
8. Vural M, Toy H, Camuzcuoglu H, Aksoy N. Comparison of prolidase enzyme activities of maternal serum and pla- cental tissue in patients with early pregnancy failure. Arch Gynecol Obstet 2011; 283:953–58.

9. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxidase in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95:351.
10. Thornton FJ, Barbul A. Healing in the gastrointestinal tract. Surg Clin North Am 1997; 77: 549-73.
11. Buyne OR, Bleichrodt RP, Verweij PE, Groenewound HM, Goor HV, Hendriks T. A peritonitis model with low mor- tality and persisting intra-abdominal abscesses. Int J Exp Pathol 2006; 87: 361-68.
12. Naycı A, Çömlekoğlu Ü, Çıngı E. “Does sepsis impair the healing of colonic anastomosis in splenectomized rats?” National Trauma J (Turkish) 2005; 11: 282-6.
13. Kılıçoğlu B, Kılıçoğlu SS, Eren VÇ. Wound healing in gas- trointestinal system. SDÜ Medical Faculty J (Turkish) 2005;12: 67-76.
14. Giray S. Effects of hyperbaric oxygen and pentoxifylline on colonic anastomosis in rats applied preoperative radio- therapy İÜ Cerrahpaşa Medical Faculty, General Surgery Thesis, İstanbul, 2000.
15. Shandall A, Lowndes R, Young HL. Colonic anastomotic healing and oxygen tension. Br J Surg 1985; 72: 606-9.
16. Garcia JJ, Reiter RJ, Guerrero JM, Escames G, Yu BP, Oh CS and all. Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation. FEBS Lett 1997; 408:297-00.
17. Athar HR, Khan A, Ashraf M. Exogenously applied ascor- bic acid alleviates saltinduced oxidative stress in wheat. Environ Exp Botany 2008; 63: 224-31.
18. Shahidi S, Komaki A, Mahmoodi M, Atrvash N, Ghodrati M. Ascorbic acid supplementation could affect passive avoid- ance learning and memory in rat. Brain Res Bull 2008; 76:109-13.
19. Schwartz S, Shires GT, Spencer FC, Daly JM, Fischer JE, Galloway AC. Principles of Surgery, seventh edition, Ankara 2004; 269-303.
20. Liang JF, Akaike T. Inhibition of nitric oxide synthesis in primary cultured Mouse hepatocytes by α-lipoic acid. Chem Biol Interact 2000;124:53-60.
21. Wolz P, Krieglstein J. Neuroprotective effects of alpha lipoic acid its enantiomers demonstrated in rodent mod- els of focal cerebral ischemia. Neuropharmacology 1996; 35:369-75.
22. Lee SR, Im KJ, Suh S, Jung JG. Protective effect of green tea polyphenol (-) epigallocatechin gallete and other an- tioxidants on lipid peroxidation in gebril brain homog- enates. Phytother Res 2003;17:206-9.
23. Kaplan B, Gönül B, Dinçer S, Kaya ND, Babül A. Relationships Between Tensile Strength, Ascorbic Acid, Hydroxyproline and Zinc Levels of Rabbit Full-Thickness Incision Wound Healing. Surg Today 2004; 34: 747-51.
24. Bishop A, Anderson JE. NO signaling in the CNS: From the physiological to the pathological. Toxicology 2005; 208:193–205.
25. Membrives P, Ruiz V, Severin C, Aquilar J, Mendez V. Effect of pentoxifyline on the healing of ischemic colorektal anastomoses. Dis Colon Rectum 2006; 50: 369-750.
26. Harnet JJ, Auguet M, Viossat I, Dolo C, Bigg D, Chabrier PE. Novel lipoic acid analogues that inhibit nitric oxide synhase. Bioorganic & Medicinal chemistry Letters 2002; 12:1439-42.
27. Miltyk W, Surazynski A, Kasprzak KS, Fivash MJ Jr, Buzard GS, Phang JM. Inhibition of prolidase activity by nickel causes decreased growth of proline auxotrophic CHO cells. J Cell Biochem 2005; 94:1210–7.
28. Oono T, FujiwaraY, Yoshioka T, Arata J. Prolidase activity in chronic wound and blister fluids. J Dermatol 1997; 24: 626-9.
29. Çadirci E, Altunkaynak BZ, Halici Z. Alpha lipoic acid as a potential target for the treatment of lung Injury caused by cecal ligation and puncture-ınduced Sepsis model in rats. Shock 2010;33: 479-84.
30. Balachandar AV, Malarkodi KP, Varlakshmi P. “Protective role of DL alphalipoic acid against adriamycin-induced cardiac lipid peroxidation. ” Hum Exp Toxicol 2003; 22: 249-54.
31. Malarkodi KP, Balachandar AV, Varlakshmi P. The influence of lipoic acid on adriamycin-induced hyperlipidemic neph- rotoxicity in rats. Mol Cell Biochem 2003; 247: 139-45.
32. Odabasoglu F, Halici Z, Aygun H, et al. Anti-inflammatory effect of the alpha-lipoic acid on carrageenan-induced paw edema in rats and its relation with lipid peroxida- tion level and myeloperoxidase activity. The 32nd FEBS Congress BMolecular Machines, [ Vienna, July 7Y12, 2007; FEBS J 274 (Suppl 1):269
33. Arivazhagan P, Juliet P, Panneerselyam C. Effect of dl-al- pha-lipoic acid on the status of lipid peroxidation and an- tioxidants in aged rats. Pharmacol Res 2000; 41:299-303.