The Protective Effects of Silymarin on D-Galactosamine/Tumor Necrosis FactorAlpha-Induced Oxidative Stress and Lung Injury in Mice

Öz

Silymarin (Sm) is known for its anti-oxidative, anti-inflammatory, and antimitotic activities against a broad range of cancers, such as prostate, colon, ovarian, skin and lung cancer. This study targets to determine the protective effects of Sm on lung damage in the mice exposed to D-galactosamine (D-GaIN)/tumour necrosis factor alpha (TNF-α). For this purpose, three groups of Balb/c mice were used. The study groups were given saline (0.5 mL), D-GalN/TNF-a, and D-GaIN/TNF-α plus Sm, respectively. Our biochemistry, apoptotic markers and light microscopic findings offer that Sm can noticeably diminish D-GaIN/TNFα-induced pulmonary toxicity. In conclusion, Sm improves degenerative alterations in injured lung owing to D-GalN/TNF-a. This caring effect might be thanks to the capability of Sm to keep oxidant–antioxidant stability. 

Anahtar Kelimeler

• D-galactosamine,Silymarin,Tumour necrosis factor alpha,Apoptotic marker,Lung damage

D-Galaktozamin/Tümör Nekroz Faktör Alfa Nedenli Oksidatif Stress ve Akciğer Hasarı Üzerine Silmarinin Koruyucu Etkileri

Öz

Silymarin (Sm), prostat, kolon, yumurtalık, deri ve akciğer kanseri gibi çok çeşitli kanserlerin tedavisinde kullanılan anti-oksidatif, anti-inflamatuar ve anti-mitotik aktiviteleri ile bilinen bir bileşiktir. Bu çalışma, D-galaktosamin (D-GaIN) / tümör nekrozis faktör alfa (TNF-α) nedenli oksidatif stress ve akciğer hasarı üzerinde Sm’nin koruyucu etkilerini belirlemeyi amaçlamaktadır. Bu amaçla 21 adet Balb / c cinsi erek fare kullanıldı (n=7). Çalışma gruplarına sırasıyla serum fizyolojik (0.5 mL), D-GalN / TNF-a ve D-GaIN / TNF-α artı Sm verildi. Biyokimyasal, histopatolojik ve apoptotik bulgularımıza göre, Sm'nin D-GaIN / TNF-a nedenli pulmoner toksisiteyi ve oksidatif stressi belirgin olarak azaltabildiğini göstermektedir. Sonuç olarak, Sm, D-GalN / TNFa'ya bağlı akciğerde meydana gelen dejeneratif değişiklikleri olumlu yönde iyileştirdiği görülmüştür. Sm’nin bu etkisi, oksidan-antioksidan stabilitesini koruma özelliğinden dolayı olduğunu düşünmekteyiz.

Anahtar Kelimeler

• D-galaktozamin,Simarin,Tümör nekroz faktör,Apoptotic marker,Akciğer hasarı

Kaynakça

1. 1. Azarkhiavi K.R., Ali-Omrani M, Solgi R, Bagheri P Haji-Noormohammadi M, Amani N, and Sepand MR 2014. Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice. Pharm Biol, 52(10): 1267–1271
2. 2. Chopra M, Reuben JS, Sharma AC (2009) Acute lung injury: apoptosis and signaling mechanisms. Exp Biol Med (Maywood) 234(4):361–371. doi:10.3181/0811-MR-318.
3. 3. Feng G, Liu S, Wang GL et al (2008) Lidocaine attenuates lipopolysaccharide-induced acute lung injury through inhibiting NF-kB activation. Pharmacology 81:32–40
4. 4. Fong Y, Moldawer LL, Shires GT, Lowry SF (1990) The biologic characteristics of cytokines and their implication in surgical injury. Surg Gynecol Obstet 170:363–378
5. 5. Gazak R, Walterova D, Kren V. (2007). Silybin and silymarin – New and emerging applications in medicine. Curr Med Chem 14:315–38.
6. 6. Gezginci S and Bolkent S The effect of Z-FA.FMK on D-galactosamine/ TNF-α-induced liver injury in mice cell, Biochemistry and function Cell Biochem Funct,25, 277–286 2007.
7. 7. Gezginci-Oktayoglu S, Tunali S, Yanardag R et al (2008) Effects of Z-FA.FMK on D-galactosamine/tumor necrosis factor-alphainduced kidney injury and oxidative stress in mice: effects of Z-FA.FMK on TNF-alpha-mediated kidney injury. Mol Cell Biochem 309:9–20
8. 8. Haston CK, Travis EL (1997) Murine susceptibility to radiationinduced pulmonary fibrosis is influenced by a genetic factor implicated in susceptibility to bleomycin-induced pulmonary fibrosis. Cancer Res 57:5286–5291.

9. 9. Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS. (2007). Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. J Surg Res 143:58–65
10. 10. Jin Y, Zhao X, Zhang H, Li Q, Lu G and Zhao X. 2016. Modulatory effect of Silymarin on pulmonary vascular dysfunction through Hif-1A-iNOS following rat lung ischemia-reperfusion injury. Experimental and therapeutic medicine. 12: 1135-1140, 2016
11. 11. Lee WL, Downey GP (2001) Neutrophil activation and acute lung injury. Curr Opin Crit Care 7:1–7
12. 12. Leist M, Gantner F, Bohlinger I et al (1994) Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-alpha requires transcriptional arrest. J Immunol 153:1778–1788
13. 13. Leist M, Gantner F, Bohlinger I et al (1995) Tumor necrosis factor-induced hepatocyte apoptosis precede sliver failure in experimental murine shock models. Am J Pathol 146:1220–1234
14. 14. Matuschak GM, Pinsky MR, Klein EC et al (1990) Effects of D-galactoseamine-induced acute liver injury on mortality and pulmonary responses to Escherichia coli lipopolysaccharide. Modulation by arachidonic acid metabolites. Am Rev Respir Dis 141(5 Pt 1):1296–1306
15. 15. Muriel P, Mourelle M Prevention by silymarin of membrane alterations in acute CCI4 liver damage. J. Appl. Toxicol. 10 (4): 275–279 1990.
16. 16. Milić N, Milosević N, Suvajdzić L, Zarkov M, Abenavoli L. New therapeutic potentials of milk thistle (Silybum marianum). Nat Prod Commun. 2013;8(12):1801-10.
17. 17. Mukarram Shah SM, Khan FA, Hassan Shah SM, et al. (2011). Evaluation of phytochemicals and antimicrobial activity of white and blue capitulum and whole plant of Silybum Marianum. World Appl Sci J 12:1139–44
18. 18. Mukhopadhyay S, Hoidal JR, Mukherjee TK (2006) Role of TNF-a in pulmonary pathophysiology. Respir Res 7:125–133
19. 19. Oliveira C, Lopasso FP, Laurindo F, et al. (2001). Protection against liver ischemia reperfusion injury in rats by silymarin or verapamil. Transplant Proc 33:3010–14
20. 20. Oztay F, Gezginci-Oktayoglu S, Bayrak BB, Yanardag R, Bolkent S. 2010. Cathepsin B inhibition improves lung injury associated to D-galactosamine/tumor necrosis factor-alpha-induced liver injury in mice. Mol Cell Biochem (2010) 333:65–72
21. 21. Quinlan T, Spivack S, Mossman BT. (1994). Regulation of antioxidant enzymes in lung after oxidant injury. Environ Health Perspect 2: 79–87.
22. 22. Pang XP, Hershman JM, Pekary AE (1991) Plasma disappearance and organ distribution of recombinant human tumor necrosis factor-alpha in rats. Lymphokine Cytokine Res10:301–306
23. 23. Siore AM, Parker RE, Stecenko AA et al (2005) Endotoxin induced acute lung injury requires interaction with the liver. Am J Physiol Lung Cell Mol Physiol 289(5):L769–L776 40.
24. 24. Spapen H, Zhang H, Demanet C et al (1998) Does N-Acetyl-L Cysteine influence cytokine response human septic shock? Chest 113:1616–1624
25. 25. Wang R, Alam G, Zagariya A et al (2000) Apoptosis of lung epithelia lcells in response to TNF-alpha requires angiotensin II generation de novo. J Cell Physiol 185:253–25
26. 26. Wen Z, Dumas TE, Schrieber SJ, Hawke RL, Fried MW, Smith PC. Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract. Drug Metab Dispos. 2008;36(1):65-72.