Protective Effects of Silymarin on Indomethacin-Induced Gastric Ulcer in Rats

Yıl 2019, , 109 - 114, 08.08.2019

Murat Boyacıoğlu

https://doi.org/10.32707/ercivet.595636

Cited By: 1

Öz

Silymarin is a natural antioxidant
polyphenolic flavonoid structure, it has been reported to be effective against
free radicals and reactive oxygen species. Indomethacin is a nonsteroidal
anti-inflammatory drug and can promote ulcer in gastric tissue. The purpose of
this study was to investigate the protective
effects of silymarin on indomethacin-induced gastric ulcer model. Forty two
male Wistar albino rats were divided
into 6 groups (n=7); control, indomethacin, lansoprazole+indomethacin,
silymarin (25, 50 and 100 mg/kg)+indomethacin group. Different doses of
silymarin were administered by oral gavage and then gastric ulcers were induced
by oral administration of indomethacin (25 mg/kg). Ulcer protective activity of
silymarin was compared with lansoprazole (30 mg/kg). The rats were euthanized 6
h after indomethacin exposure. Activities of superoxide
dismutase (SOD), catalase (CAT) and myeloperoxidase
(MPO) as well as malondialdehyde
(MDA) and glutathione (GSH) levels were determined in stomach tissue. Gastric tissue was also assessed in terms of
macroscopic as ulcerative areas. As a result, 100 mg/kg silymarin was
showed antiulceratif effects. The same dose of silymarin significantly
decreased MDA level and MPO activity, and increased SOD activity
and GSH level in stomach tissue. Silymarin might have a protective effect against
indomethacin-induced gastric ulcer as well as oxidative stress in rat.

Anahtar Kelimeler

Indomethacin, gastric ulcer, rat, silymarin

Ratlarda İndometazinle Oluşturulan Gastrik Ülser Üzerine Silimarinin Koruyucu Etkileri

Öz

Doğal
polifenolik yapılı flavonoid bir antioksidan olan silimarinin serbest
radikallere ve reaktif oksijen türlerine karşı etkili olduğu bildirilmiştir.
İndometazin, nonsteroidal anti-inflammatuar bir ilaç olup mide ülseri yapıcı etkileri
bulunmaktadır. Bu çalışmada indometazin ile indüklenmiş mide ülseri modelinde
silimarinin koruyucu etkinliği araştırıldı. Çalışma kapsamında 42 adet erkek Wistar
albino sıçan kullanıldı ve sıçanlar kontrol, indometazin, lansoprazol+indometazin,
silimarin (25, 50 ve 100 mg/kg)+indometazin olacak şekilde altı gruba ayrıldı
(n=7). Farklı dozlarda silimarin ağızdan gavajla uygulandı ve 5 dk sonra 25
mg/kg indometazin ile gastik ülser indüklendi. Koruyucu etkinlik lansoprazol (30 mg/kg) ile karşılaştırıldı. Sıçanlar indometazin uygulamasından 6 saat sonra
ötenazi edildi. Mide dokusu superoksid dismutaz (SOD), katalaz (CAT)
ve miyeloperoksidaz (MPO) aktivitesi ile malondialdehid (MDA) ve glutatyon
(GSH) seviyesi analiz edildi. Mide dokusu aynı zamanda makroskobik olarak
ülseratif alanlar yönünden de değerlendirildi. Çalışma sonucunda 100 mg/kg
dozda silimarinin anti-ülseratif etkisinin olduğu; bu dozda verilen silimarinin
mide dokusu MDA seviyesi ve MPO aktivitesini anlamlı olarak azalttığı, SOD
aktivitesi ve GSH seviyesini arttırdığı belirlendi. Sonuç olarak indometazin ile indüklenen mide ülseri ve
oksidatif streste silimarinin koruyucu etkilerinin olabileceği kanaatine
varıldı.

Anahtar Kelimeler

İndometazin, mide ülseri, rat, silimarin

Kaynakça

• 1. Abebaw M, Mishra B, Gelayee DA. Evaluation of anti-ulcer activity of the leaf extract of Osyris quadripartita Decne. (Santalaceae) in rats. J Exp Pharmacol 2017; 9: 1-11.
• 2. Aebi H. Catalase in vitro assay methods. Methods Enzymol 1984; 105: 121-6.
• 3. Alarcon L, Martin MJ, Marhuenda E. Gastric anti-ulcer activity of silymarin, a lipoxygenase inhibitor in rats. J Pharm Pharmacol 1992; 44(11): 929-31.
• 4. Alcaraz MJ, Hoult JR. Actions of flavonoids and the novel anti-inflammatory avone, hypolaetin-8-glucoside, on prostaglandin biosynthesis and inactivation. Biochem Pharmacol 1985; 34(14): 2477-82.
• 5. Alkushi AG, Elsawy NA. Quercetin attenuates, indomethacin-induced acute gastric ulcer in rats. Folia Morphol 2017; 76(2): 252-61.
• 6. Antonisamy P, Arasu MV, Dhanasekaran M, Choi KC, Aravinthan A, Kim NS, Kang CW, Kim JH. Protective effects of trigonelline against indomethacin-induced gastric ulcer in rats and potential underlying mechanisms. Food Funct 2016; 7(1): 398-408.
• 7. Atalay F, Odabasoglu F, Halici M, Cakir A, Cadirci E, Aslan A, Berktas OA, Kazaz C. Gastroprotective and antioxidant effects of lobaria pulmonaria and its metabolite rhizonyl alcohol on indomethacin-induced gastric ulcer. Chem Biodivers 2015; 12(11): 1756-67.
• 8. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78(3): 206-9.
• 9. Bronner C, Landry Y. Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells. Agents and Actions 1985; 16(3-4): 147-51.
• 10. Carrasco-Pozo C, Castillob RL, Beltran C, Miranda A, Fuentes J, Gotteland M. Molecular mechanisms of gastrointestinal protection by quercetin against indomethacin-induced damage: role of NF-kB and Nrf2. J Nutr Biochem 2016; 27: 289-98.
• 11. Comoglio A, Leonardduzzi G, Carni R, Busolin D, Basaga H, Albano E, Tomasi A, Poli G, Morazzoni P, Magistretti MJ. Studies on the antioxidant and free radical scavenging properties of IdB 1016 a new flavanolignan complex. Free Radic Res Commun 1990; 11(1-3): 109-15.
• 12. Farzaei MH, Abdollahi M, Rahimi R. Role of dietary polyphenols in the management of peptic ulcer. World J Gastroenterol 2015; 21(21): 6499-517.
• 13. Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93(2): 139-43.
• 14. Guidobono F, Pagani F, Ticozzi C, Sibilia V, Pecile A, Netti C. Protection by amylin of gastric erosions induced by indomethacin or ethanol in rats. Br J Clin Pharmacol 1997; 120(4): 581-6.
• 15. Halıcı M, Küfrevioğlu OI, Odabaşoğlu F, Halıcı Z, Çakır A, Aslan A. The ethanol-water extract of Ramalina capitata has gastroprotective and antioxidative properties: an experimental study in rats with indomethacin-induced gastric injuries. J Food Biochem 2011; 35(1): 11-26.
• 16. Huilgol SV, Jamadar MG. Silymarin, an antioxidant bioflavonoid, inhibits experimentally-induced peptic ulcers in rats by dual mechanisms. Int J App Basic Med Res 2012; 2(1): 63-6.
• 17. Jung HS, Lee CW, Oha SJ, Yun J, Lee K, Park SK, Kim HM, Han SB, Kim Y, Kim HC, Kang J. Protective effect of silymarin against ethanol-induced gastritis in rats: Role of sulfhydryls, nitric oxide and gastric sensory afferents. Food Chem Toxicol 2013; 55: 353-7.
• 18. Kayaalp OS. Peptik ülser tedavisinde kullanılan ilaçlar. Ozdemir O. Topal G. Yıldırım A. Kayaalp O. eds. In: Akılcı Tedavi Yönünden Tıbbi Farmakoloji. Ankara: Pelikan Kitabevi, 2012; pp. 1409-22.
• 19. Keshk WA, Zahran SM, Katary MA, Ali DAE. Modulatory effect of silymarin on nuclear factor-erythroid-2-related factor 2 regulated redox status, nuclear factor-kB mediated inflammation and apoptosis in experimental gastric ulcer. Chem Biol Interact 2017; 273: 266-72.
• 20. Kim JH, Kim BW, Kwon HJ, Nam SW. Curative effect of selenium against indomethacin-induced gastric ulcers. J Microbiol Biotechnol 2011; 21(4): 400-4.
• 21. Lee IC, Baek HS, Kim SH, Moon C, Park SH, Kim SH, Shin IS, Park SC, Kim JC. Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats. Hum Exp Toxicol 2014; 34(3): 227-39.
• 22. Nguelefack TB, Feumebo CB, Ateufack G, Watcho P, Tatsimo S, Atsamo D, Tane P, Kamanyi A. Anti-ulcerogenic properties of the aqueous and methanol extracts from the leaves of Solanum torvum Swartz (Solanaceae) in rats. J Ethnopharmacol 2005; 119(1): 135-40.
• 23. Odabaşoğlu F, Halici Z, Cakir A, Halici M, Aygun H. Beneficial effects of vegetable oils (corn, olive and sunflower oils) and α-tocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin in rats. Eur J Pharmacol 2008; 591(1-3): 300-6.
• 24. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-8.
• 25. Park SH, Hong H, Han YM, Kangwan N, Kim SJ, Kim EH, Hahm KB. Nonsteroidal anti-inflammatory drugs (NSAID) sparing effects of glucosamine hydrochloride through N-glycosylation inhibition; strategy to rescue stomach from NSAID damage. J Physiol Pharmacol 2013; 64(2): 157-65.
• 26. Perez Y, Oyarzabal A, Mas R, Molina V, Jimenez S. Protective effect of D-002, a mixture of beeswax alcohols, against indomethacin-induced gastric ulcers and mechanism of action. J Nat Med 2013; 67(1): 182-9.
• 27. Polat B, Albayrak Y, Süleyman B, Dursun H, Odabaşoğlu F, Yiğiter M, Halıcı Z, Süleyman H. Antiulcerative effect of dexmedetomidine on indomethacin-induced gastric ulcer in rats. Pharmacol Rep 2011; 63(2): 518-26.
• 28. Sinha K, Sil PC. Targeting oxidative stress and inflammation in NSAIDs induced gastropathy: A plausible therapeutic approach. Inflamm Cell Signal 2015; 2: e763.
• 29. Sun Y, Oberley LW, Li Y. A simple for clinical assay of superoxide dismutase. Clin Chem 1988; 34(3): 497-500.
• 30. Surai PF. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants 2015; 4(1): 204-47.
• 31. Swarnakar S, Ganguly K, Kundu P, Banerjee A, Maity P, Sharma AV. Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer. J Biol Chem 2005; 280(10): 9409-15.
• 32. Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 1969; 27(3): 502-22.
• 33. Zaki SM, Mohamed EA. Effect of glucocorticoids on indomethacin-induced gastric ulcer in the adult male albino rat-histological, morphometric and electron microscopy study. Arch Med Sci 2014; 10(2): 381-8.