Document Type : Original Article
Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
The present study aimed to examine the effectiveness of silymarin compared to hydrocortisone on clinical and hematological alterations and organ injury (liver and heart) in a low-dose canine lipopolysaccharide (LPS)-induced sepsis model. Fifteen clinically healthy dogs were randomly categorized into three equal groups: Two dogs in group A, LPS (0.10 μg kg-1, IV) was injected (control, n = 5); Group B was similar to group A, with the difference that silymarin bolus (10.00 mg kg-1, IV, once) was injected 40 min after LPS injection. Group C was similar to group B with the difference that hydrocortisone bolus (2.00 mg kg-1, IV, once) was administrated instead of silymarin. Five mL of blood was collected at baseline, 1, 3, and 6 hr of the study. Septic control dogs experienced a significant reduction in red blood cells count (RBC), hemoglobin (Hb), and hematocrit (HCT) and a significant elevation in serum activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), and plasma cardiac troponin I (cTnI) concentration. We noticed a significant increase in RBCs, Hb, and HCT, and a significant decrease in AST, ALP, LDH, CK-MB, and cTnI in the silymarin group in comparison with hydrocortisone and control group. Our results suggested that silymarin had a positive influence on sepsis due to protecting RBCs, and decreasing organ (heart and liver) injury. These findings supported the hypothesis that silymarin could be more effective than routine corticosteroid therapy in sepsis.
- Rau S, Kohn B, Richter C, et al. Plasma interleukin-6 response is predictive for severity and mortality in canine systemic inflammatory response syndrome and sepsis. Vet Clin Pathol 2007; 36(3): 253-260.
- Kenney EM, Rozanski EA, Rush JE, et al. Association between outcome and organ system dysfunction in dogs with sepsis: 114 cases (2003-2007). J Am Vet Med Assoc2010; 236(1): 83-87.
- Hauptman JG, Walshaw R, Olivier NB. Evaluation of the sensitivity and specificity of diagnostic criteria for sepsis in dogs. Vet Surg 1997; 26(5): 393-397.
- Silverstein D. Systemic inflammatory response syndrome and sepsis, Part 1: Recognition and Diagnosis. Today’s Vet Prac 2015; 5: 38-44.
- Baskurt OK, Gelmont D, Meiselman HJ. Red blood cell deformability in sepsis. Am J Respir Crit Care Med 1998; 157(2): 421-427.
- Goyette RE, Key NS, Ely EW. Hematologic changes in sepsis and their therapeutic implications. Semin Respir Crit Care Med 2004; 25(6): 645-659.
- Pattanaik U, Prasad K. Reactive oxygen species and endotoxic shock: effect of dimethylthiourea. J Cardiovasc Pharmacol Ther 2001; 6(3): 273-285.
- Bone RC. Gram-negative sepsis. Background, clinical features, and intervention. Chest 1991; 100(3): 802-808.
- Greiner M, Wolf G, Hartmann K. A retrospective study of the clinical presentation of 140 dogs and 39 cats with bacteremia. J Small Anim Pract 2008; 49(8): 378-383.
- Cai B, Deitch EA, Ulloa L. Novel insights for systemic inflammation in sepsis and hemorrhage. Mediators Inflamm 2010; 642462, doi: 10.1155/2010/642462.
- Yu DH, Kim B, Park J. Pathophysiologic and immunologic changes in a canine endotoxemia over a period of 24 hours. J Vet Med Sci 2012; 74(5): 537-544.
- De Vries F, Leuschner J, Jilma B, et al. Establishment of a low-dose canine endotoxemia model to test anti-inflammatory drugs: Effects of prednisolone. Int J Immunopathol Pharmacol 2013; 26(4): 861-869.
- Annane D. The role of ACTH and corticosteroids for sepsis and septic shock: An update. Front Endocrinol (Lausanne) 2016; 20(7): 70. doi: 10.3389/fendo. 2016.00070.
- Schimmer BP, Parker KL. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. InGoodman & Gilman's the pharmacological basis of therapeutics. 11th ed. Brunton L, Lazo J, Parker K (Eds). New York, USA: McGraw-Hill 2006; 1649-1677.
- Anagnostis P, Athyros VG, Tziomalos K, et al. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: A hypothesis. J Clin Endocrinol Metab 2009; 94(8): 2692-2701.
- Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments, and mechanistic insights. Mol Cell Endocrinol 2011; 335(1): 2-13.
- Shapiro H, Lev S, Cohen J, et al. Polyphenols in the prevention and treatment of sepsis syndromes: Rationale and pre-clinical evidence. Nutrition 2009; 25(10): 981-997.
- Rainone F. Milk thistle. Am Fam Physician 2005; 72(7): 1285-1288.
- Kroll DJ, Shaw HS, Oberlies NH. Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integr Cancer Ther 2007; 6(2): 110-119.
- Sherif IO, Al-Gayyar MMH. Antioxidant, anti-inflammatory and hepatoprotective effects of silymarin on hepatic dysfunction induced by sodium nitrite. Eur Cytokine Netw 2013; 24(3): 114-121.
- Nanda V, Gupta V, Sharma SN, et al. Effect of Liverubin™ on hepatic biochemical profile in patients of alcoholic liver disease: A retrospective study. Minerva Med 2014; 105(6 Suppl 2):1-8.
- Lucena MI, Andrade RJ, de la Cruz JP, et al. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int J Clin Pharmacol Ther 2002; 40(1): 2-8.
- Mengs U, Pohl RT, Mitchell T. Legalon® SIL: The antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning. Curr Pharm Biotechnol 2012; 13(10): 1964-1970.
- Fried MW, Navarro VJ, Afdhal N, et al. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: A randomized controlled trial. J Am Med Assoc 2012; 308(3): 274-282.
- Lo D, Wang YT, Wu MC. Hepatoprotective effect of silymarin on di(2-ethylhexyl) phthalate (DEHP) induced injury in liver FL83B cells. Environ Toxicol Pharmacol 2014; 38(1): 112-118.
- Srivastava RK, Sharma S, Verma S, et al. Influence of diabetes on liver injury induced by antitubercular drugs and on silymarin hepatoprotection in rats. Methods Find Exp Clin Pharmacol 2008; 30(10): 731-737.
- Zholobenko A, Modriansky M. Silymarin and its constituents in cardiac preconditioning. Fitoterapia 2014; 97: 122-132.
- Kang JS, Jeon YJ, Park SK, et al. Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1beta and prostaglandin E2 synthesis by silymarin. Biochem Pharmacol 2004; 67(1): 175-181.
- Toklu HZ, Akbay TT, Velioglu-Ogunc A, et al. Silymarin, the antioxidant component of Silybum marianum, prevents sepsis -induced acute lung and brain injury. J Surg Res 2008; 145(2): 214-222.
- Varzi HN, Esmailzadeh S, Morovvati H, et al. Effect of silymarin and vitamin E on gentamicin-induced nephrotoxicity in dogs. J Vet Pharmacol Ther 2007; 30(5): 477-481.
- Annane D. Corticosteroids for septic shock. Crit Care Med 2001; 29(7 Suppl): S117-S120.
- Papich MG. Saunders handbook of veterinary drugs: Small and large animal. 4th ed. Philadelphia, USA: Saunders 2016; 382.
- Roozbeh J, Shahriyari B, Akmali M, et al. Comparative effects of silymarin and vitamin E supplementation on oxidative stress markers, and hemoglobin levels among patients on hemodialysis. Ren Fail 2011; 33(2): 118-123.
- Adhikari M, Arora R. The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity. Environ Toxicol 2016; 31(6): 641-654.
- Wang PY, Kaneko T, Tsukada H, et al. Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: Comparison of biochemical and histo-pathological changes. Arch Toxicol 1997; 71(10): 638-645.
- Hou YC, Liou KT, Chern CM, et al. Preventive effect of silymarin in cerebral ischemia–reperfusion-induced brain injury in rats possibly through impairing NF-κB and STAT-1 activation. Phytomedicine 2010; 17(12): 963-973.
- Turgut F, Bayrak O, Catal F, et al. Antioxidant and protective effects of silymarin on ischemia and reperfusion injury in the kidney tissues of rats. Int Urol Nephrol 2008; 40(2): 453-460.
- Senturk H, Kabay S, Bayramoglu G, et al. Silymarin attenuates the renal ischemia/reperfusion injury-induced morphological changes in the rat kidney. World J Urol 2008; 26(4): 401-407.
- Alarcón de la Lastra AC, Martín MJ, Motilva V, et al. Gastroprotection induced by silymarin, the hepatoprotective principle of Silybum marianum in ischemia-reperfusion mucosal injury: Role of neutrophils. Planta Med 1995; 61(2): 116-119.
- Tuorkey MJ, El-Desouki NI, Kamel RA. Cytoprotective effect of silymarin against diabetes-induced cardio-myocyte apoptosis in diabetic rats. Biomed Environ Sci 2015; 28(1): 36-43.
- Taghiabadi E, Imenshahidi M, Abnous K, et al. Protective effect of silymarin against acrolein-induced cardiotoxicity in mice. Evid Based Complement Alternat Med 2012; 2012: 352091. doi: 10.1155/2012/352091.
- El-Awady El-SE, Moustafa YM, Abo-Elmatty DM, et al. Cisplatin-induced cardiotoxicity: Mechanisms and cardioprotective strategies. Eur J Pharmacol 2011; 650(1): 335-341.
- Rao PR, Viswanath RK. Cardioprotective activity of silymarin in ischemia– reperfusion-induced myocardial infarction in albino rats. Exp Clin Cardiol 2007; 12(4), 179-187.
- Salamone F, Galvano F, Gammazza AM, et al. Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis. Dig Liver Dis 2012; 44(4): 334-342.