The effect of silymarin on the liver in thermal burn injury

Year 2014, Volume: 18 Issue: 2, 56 - 61, 16.05.2014

Evren Yemişen Ayşen Yarat Tuğba Tunalı Akbay Hale Toklu Göksel Şener

Abstract

Hepatic homeostasis and metabolism are essential for survival
in critically ill and severely burned patients. Silymarin,
the major component of thistle milk has been shown to have
hepatoprotective effect. In this study the effect of silymarin
on the liver of burned rats was investigated. Wistar Albino
rats were exposed to 900C bath for 10 seconds to induce skin
burn. Silymarin either locally (30 mg/kg) applied on 4 cm2
area or locally+systemically (50 mg/kg p.o) was administered
after burn and repeated twice daily. Rats were decapitated
48 h after injury and blood was collected for tumor necrosis
factor-α (TNF- α) and lactate dehydrogenase (LDH)
activity. In liver tissue samples, total protein, tissue factor
activity (TF) and activities of carbonic anhydrase (CA), glutathione-
S-transferase (GST), catalase (CAT), superoxide
dismutase (SOD), alkalen and acid phosphatase (ALP, ACP
respectively) enzymes were determined. In addition polyacyrlamid
gel electrophoresis was carried on liver tissue samples.
Burn caused a significant increase in blood TNF- α and
LDH levels. Total protein levels and ALP activity increased
and SOD activity decreased in the liver tissue at 48h
after burn. Both local and systemic silymarin treatment
significantly reversed this parameters except ALP. Silymarin
treatment significantly increased ALP activity. Local
silymarin treatment increased, CAT and ACP activities and
decreased TF activity compared to control and burn group;
and increased CA activity compared to systemic+local silymarin
treatment. Addition of systemic silymarin treatment
to local silymarin treatment reversed these effects of local
treatment to control group levels. Non significant differences
were found between protein bands obtained in electrophoresis.
Minor liver damage was obvious 48 h after thermal
skin burn. Both local and systemic silymarin treatment
were effective to reverse the effects of burn induced liver
injury.
Key Words: Burn, liver enzymes, liver tissue factor activity,
SDS-polyacrylamide gel electrophoresis, silymarin

Keywords

Burn, liver enzymes, liver tissue factor activity, SDS-polyacrylamide gel electrophoresis, silymarin

ORIGINAL RESEARCH

Abstract

Karaciğer yanık hastaları için hayati önem taşır. Meryamana dikeninin ana maddesi olan silmarinin karaciğer üzerindeki koruyucu etkisi gösterilmiştir. Bu çalışmada termal deri yanıklı sıçanlarda silmarinin karaciğer üzerine etkisi araştırıldı. WistarAlbino türü sıçanlar 90oC deki su ile 10 saniye temas ettirilerek deri yanığı oluşturuldu. Silmarin hem lokal (30 mg/kg) olarak hemde lokal + oral yolla (50 mg/kg) yanık oluşturulduktan sonra 2 gün (48 saat) süre ile günde 2 kez uygulandı. 48 saat sonunda sıçanlar dekapite edildi ve kan örneklerinde tümör nekroz faktör (TNF-α) ve laktat dehidrogenaz (LDH) aktivitesi incelendi, karaciğer dokusunda protein, doku faktörü (DF) aktivitesi, karbonik anhidraz (CA), glutatyon-S-transferaz (GST), katalaz (CAT), süperoksid dismutaz (SOD), alkalen fosfataz (ALP), asit fosfataz (ACP) gibi enzim aktiviteleri tayin edildi. Ayrıca SDS

Keywords

Karaciğer doku faktörü aktivitesi, Karaciğer enzimleri, SDS-poliakrilamid jel elektroforezi, Silmarin, Yanık

References

• Price LA, Thombs B, Chen CL, Milner SM. Liver disease in Burn injury: Evidence from a National sample of 31338 adults patients. J Burns Wounds 2007; 7:1-11.
• Schwacha MG, Somers SD. Thermal injury induced enhancement of oxidative metabolism by mononuclear phagocytes. J Burn Care Rehabil 1999;20:37-42.
• Supple KG. Physiological response to burn injury. Crit Care Nurs Clin North Am 2004; 16:119-26.
• Jeschke MG, Micak Rp, Finnerty CC, Herdon DN. Changes in liver function and size after a severe thermal injury. Shock 2007;28:172-7.
• Jeschke MG. The hepatic response to a thermal injury. In: Total Burn Care. Ed. Hemdon DN, WB Saunders. London. 2002, pp.361-378.
• Bartlett RH, FongSW, Marrujo G, Hardeman T, AndersonW. Coagulation and platelet changes after thermal injury in man. Burns 1981;7:370-7.
• Eurenius K, Mortensen PF, Meserol PM, Curreri PW. Platelet and megakaryocyte kinetics following thermal injury. J Lab Clin Med 1971;79:147–57.
• Eurenius K, Rossi TD, McEuen DD, Arnold J, McManus WF. Blood coagulation in burn injury. Proc Soc Exp Biol Med 1974;147:878-82.
• Xia ZF, Coolbaugh MI, He F, Herdon DN, Papaconstantinou J. The effects of burn injury on the acute phase response. J Trauma 1992; 32:245-51.
• Tilg H, Dinarello CA, Mier JW. IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today 1997; 18:428-32.
• Jaehde U, Sorgel F. Clinical pharmacokinetics in patients with burns. Clin Pharmacokinet 1995; 29:15–28.
• Bonate PL. Pathophysiology and pharmacokinetics following burn injury. Clin Pharmacokinet 1990; 18:118-30.
• Tunali T, Sener G, Yarat A, Emekli N. Melatonin reduces oxidative damage to skin and normalizes blood coagulation in a rat model of thermal injury. Life Sci 2005;76: 1259-66.
• Çakır B Cevik H, Contuk G, Ercan F, Eksioglu-Demiralp E, Yegen BC. Leptin ameliorates burn induced multiple organ damage and modulates postborn immune response in rats. Regul Pep 2005;125:135-44.
• Editor: Montvale NJ, Medical Economics Company. 2000, pp.516
• Wellington K, Jarvis B. Silymarin: A review of its clinical proporties in the management of hepatic disorders. Biodrugs 2001;15: 465-89.
• Kidd P, Head K. A review of the bioavailability and clinical efficacy of milk thistle phytosome: A silybin-phosphatidylcholine complex (Siliphos). Altern Med Rev 2005; 10:193-203.
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin phenol reagent. J Biol Chem 1951;193:265
• Ingram GIC, Hills M. Reference method for the one stage prothrombin time test on human blood. Thromb Haemostas 1976;36: 237Verpoorte JA, Mehta S, Edsall JT. Esterase activities of human carbonic anhydrases B and C. J Biol Chem 1967; 242: 4221-9.
• Habig WH, Jacoby WB. Assays for differentation of glutathion-stransferases. Methods Enzymol 1981;77:398-405.
• Aebi H.Catalase Invitro. In: Methods of Enzymatic Analysis. Ed: Bergmeyer HU, John Wiley & Sons. USA. 1974, pp. 121-26.
• Mylorie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of cupper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986;82: 512-520.
• Walter K, Schült C.Acid and alkaline phosphatase in serum (two point method). In: Methods of Enzymatic Analysis. Ed: Bergmeyer HU, John Wiley & Sons. USA. 1974, pp.856-86.
• Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-5.
• Ding HQ, Zhou BJ, Liu L, Cheng S. Oxidative stress and metallothionein expression in the liver of rats with severe thermal injury. Burns 2002; 28: 215-21.
• Schwacha MG, Somers SD. Thermal injury induced enhancement of oxidative metabolism by mononuclear phagocytes. J Burn Care Rehabil 1999;20:37–41.
• Cetinkale O, Kenukoglu D, Senel O, Kemerli GD, Yazar S. Modulating the function of neutrophils and lipid peroxidation by FK-506 in a rats model of thermal injury. Burns 1999;25:105-12.
• Sayeed MM. Neutrophil signaling alteration: an adverse inflammatory response after burn shock. Medicina (B Aires) 1998;58:386-92.
• Nishigaki I, Hagihara M, Hiramatsu M, Izawa Y, Yagi K. Effect of thermal injury on lipid peroxide levels of rat. Biochem Med 1980;24:185–9.
• Toklu HZ, Tunali-Akbay T, Erkanlı G, Yüksel M, Ercan F, Şener G.Silymarin, the antioxidant component of Silybum marianum, protects against burn-induced oxidative skin injury. Burns 2007;33:908-16.
• Dorai T, Aggarwal BB. Role of chemopreventive agents in cancer therapy. Cancer Lett 2004;215:129-40.
• Chang JW, Kim CS, Kim SB, Park SK, Park JS, Lee SK. Proinflammatory cytokine-induced NF-kappaB activation in human mesangial cells is mediated through intracellular calcium but not ROS: effects of silymarin. Nephron Exp Nephrol 2006;103:156-65.
• Schumann J, Prockl J, Kiemer AK, Vollmar AM, Bang R, Tiegs G. Silibinin protects mice from T cell-dependent liver injury. J Hepatol 2003;39:333–40.
• Meeran SM, Katiyar S, Elmets CA, Katiyar SK. Silymarin inhibits UV radiation-induced immunosuppression through augmentation of interleukin-12 in mice. Mol Cancer Ther 2006;5:1660-8.
• Latha B, Ramarrishnan M, Jayaraman V, Babu M.Serum enzymatic changes modulated using trypsin:chymotrypsin preparation during burn wounds in humans. Burns 1997;23: 560-4.
• Jeschke MG, Herndon DN,Wolf SE, et al. Recombinant human growth hormone alters acute phase reactant proteins, cytokine expression, and liver morphology in burned rats. J Surg Res 1999; 83:122-9.
• Greenwald RA.Superoxide dismutase and catalase as therapeutic agents for human disease. A critical review. Free Radic Biol Med 1990; 8:201-9.
• Guemouri L, Artur Y, Herbeth B, Jeandel C, Cuny G, Siest G. Biological variability of superoxide dismutase, glutathione peroxidase, and catalase in blood. Clin Chem 1991;37:1932-1937.
• Kawai S, Komura J. Experimental burn-induced changes in lipid peroxidelevels, and activity of superoxide dismutase and glutathione peroxidase in skin lesions,serums, and liver of mice. Arch Dermatol Res 1988;280:171-5.
• Naziroglu M, Kokcam I, Yilmaz S.Beneficial effects of intraperitoneally administered alpha-tocopheryl acetate on levels of lipid peroxide and activity of glutathione peroxidase and dismutase in skin, blood and liver of thermally injured guinea pigs. Skin Pharmacol Appl Skin Physiol 2003;16:36-45.
• Saitoh D, Okada Y, Ookawara T, Yamashita H, Takahara T, Ishihara S, Ohno H, Mimura K. Prevention of ongoing lipid peroxidation by wound excision and superoxide dismutase treatment in the burned rat. Am J Emerg Med 1994;12: 142-6
• Ramakrishnan G, Raghavendran HR, Vinodhkumar R, Devaki T. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem Biol Interact 2006;161:104–14.
• Jeong DH, Lee GP, Jeong WI, Do SH, Yang HJ, Yuan DW, et al. Alterations of mast cells and TGF-beta1 on the silymarin treatment for CCl(4)-induced hepatic fibrosis. World J Gastroenterol 2005;11:1141-8.
• Nencini C, Giorgi G, Micheli L. Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine 2007;14:129-35.
• Skottova N, Kazdova L, Oliyarnyk O, Vecera R, Sobolova L, Ulrichova J. Phenolics-rich extracts from Silybum marianum and Prunella vulgaris reduce a high-sucrose diet induced oxidative stress in hereditary hypertriglyceridemic rats. Pharmacol Res 2004;50:123-30.
• Pham TN, Cho K, Warren AJ, Greenhalgh GD. Reduced hepatic expression of glutathion S-transferases in burned mice. J Trauma 2004;57:867-71.
• Bachlie E. History of thromboplastin. Br J Haematol 2000;110:248–
• Ashkinazi IIa. Functional deficiency of erythrocyte tissue factor. Bull Exp Biol Med 1997;83:664–6.
• Lwaleed BA. Tissue factor:biological function and clinical significance. Saudi Med J 2002;23:135–43.
• Tutuarima JA, Hische EAH, Trotsenburg L, Helm HJ. Thromboplastic activity of cerebrospinal fluid in neurological disease. Clin Chem 1985;31: 99-100.
• Yarat A, Tunali T, Pisiriciler R, Akyuz S, Ipbuker A, Emekli N. Salivary thromboplastic activity in diabetics and healthy controls. Clin Oral Investing 2004;8: 36-9.
• Emekli-Alturfan E, Kasikci E, Yarat A. Tissue factor activities of streptozotocin induced diabetic rat tissues and the effect of peanut consumption. Diabetes Metab Res Rev 2007;23: 653-8.
• Aktop S, Emekli-Alturfan E, Ozer C, Gonul O, Garip H, Yarat A, Goker K. Effects of Ankaferd Blood Stopper and Celox on the tissue factor activities of warfarin-treated rats. Clin Appl Thromb Hemost 2014;20: 16-21.