Streptozotosin ile İndüklenen Diyabetik Sıçanlarda Sinapik Asidin Hepatoprotektif Etkileri

Year 2021, Volume: 11 Issue: 3, 410 - 416, 01.12.2021

Fikret Altındağ

Abstract

Amaç: Hepatotoksisite diyabetin en önemli sekonder komplikasyonlarından biridir. Diyabetin neden olduğu karaciğer hasarının ana nedenleri oksidatif stres ve inflamasyondur. Sinapik asidin güçlü bir antioksidan ve antiinflamatuar olduğu öne sürülmüştür. Bu çalışmada, deneysel diyabet modelinde sinapik asidin (SA) hepatoprotektif etkilerini TNF-α, AST, ALT seviyeleri, MT boyama yoğunluğu ve histolojik değişiklikleri değerlendirerek araştırmayı amaçladık.
Materyal ve Metot: Sıçanlar dört gruba ayrıldı (n=7): Sham (S), SA, Diyabetik (D), Diyabetik+Sinapik Asit (D+SA). S grubuna intragastrik (i.g.) yolla serum fizyolojik verildi. SA grubuna 28 gün boyunca i.g. yolla 20 mg/kg/gün SA verildi. D grubuna tek doz 50 mg/kg STZ intraperitoneal (i.p.) enjekte edildi. D+SA grubuna, tek doz 50 mg/kg STZ i.p. yolla enjekte edildi ve 28 gün boyunca 20 mg/kg/gün SA i.g. yolla verildi. Tümor nekroz faktör-alfa (TNF-α) ekspresyonu immünohistokimyasal yöntemle değerlendirildi. Karaciğerde olası fibrozisi değerlendirmek için Masson’s trichrome (MT) boyası ve histolojik inceleme için hematoksilen-eozin (H-E) boyası ile karaciğer boyandı. Ayrıca karaciğer fonksiyon testleri olan serum AST ve ALT seviyeleri ölçüldü.
Bulgular: S ve SA grupları normal histolojik mimariye ve negatif TNF-a immüno-ekspresyonuna sahipti. S grubu ile karşılaştırıldığında, D grubu daha yüksek AST ve ALT seviyelerine ve MT boyama
yoğunluğuna sahipti. D grubunda şiddetli TNF-α immün ekpresyonunun yanı sıra vasküler dilatasyon, apoptotik hücreler ve inflamatuar hücrelerin infiltrasyonu gibi histopatolojik değişiklikler
gözlendi. D grubu ile karşılaştırıldığında D+SA grubunda TNF-α immunoexpression, histopatolojik değişiklikler, AST ve ALT seviyeleri azaldı.
Sonuç: Çalışmamız, STZ ile indüklenen diyabetik sıçanlarda SA’nın hepatotoksisiteye karşı hepatoprotektif bir etkiye sahip olabileceğini ortaya koydu.

Keywords

diyabet, karaciğer, sıçan, sinapik asit, TNF-α

References

• 1. El-Naggar ME, Al-Joufi F, Anwar M, Attia MF, El-Bana MA. Curcumin-loaded PLA-PEG copolymer nanoparticles for treatment of liver inflammation in streptozotocininduced diabetic rats. Colloids and Surfaces B Biointerfaces 2019;177:389–398.
• 2. Mohamed J, Nazifah AHN, Zariyantey AH, Budin SB. Mechanisms of Diabetes-Induced Liver Damage. Sultan Qaboos Univ Med J 2016;16(2):132–141.
• 3. Tolman KG, Fonseca V, Dalpiaz A, Tan MH. The spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease, Diabetes Care 2007;30:734–743.
• 4. Nambirajan G, Karunanidhi K, Ganesan A, Rajendran R, Kandasamy R, Elangovan A, Thilagar S. Evaluation of antidiabetic activity of bud and flower of Avaram Senna (Cassia auriculata L.)In high-fat diet and streptozotocin-induced diabetic rats. Biomedicine & Pharmacotherapy 2018;108:1495– 1506.
• 5. Chandirasegaran G, Elanchezhiyan C, Ghosh K, Sethupathy S. Berberine chloride ameliorates oxidative stress, inflammation, and apoptosis in the pancreas of Streptozotocin induced diabetic rats. Biomedicine & Pharmacotherapy 2017;95:175–185.
• 6. Ziamajidi N, Nasiri A, Abbasalipourkabir R, Moheb SS. Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes. Pharmaceutical Biology 2017;55(1):526–531.
• 7. Jia Q, Yang R, Liu XF, Ma SF, Wang L. Genistein attenuates renal fibrosis in streptozotocin‑induced diabetic rats. Mol Med Rep2019;19(1):423–431.
• 8. Guven A, Yavuz O, Cam M, Ercan F, Bukan N, Comunoglu C, Gokce F. Effects of melatonin on streptozotocin-induced diabetic liver injury in rats. Acta Histochem 2006;108:85–93.
• 9. Zych M, Wojnar W, Borymski S, Szałabska K, Bramora P, Kaczmarczyk-Sedlak I. Effect of rosmarinic acid and sinapic acid on oxidative stress parameters in the cardiac tissue and serum of type 2 diabetic female rats. Antioxidants 2019;8(12):579–579.
• 10. Kanchana G, Shyn WJ, Malini P, Rajadurai M. Effect of sinapic acid on antiperoxidative and antioxidant potential in normal and streptozotocin-induced diabetes in Wistar rats. Int J Pharm Clin Res 2011;3(1):5–9.
• 11. Alaofi AL, Ahmed Khan T, Criscuolo D, Ahmad Ansari M. Sinapic Acid Ameliorates the Progression of Streptozotocin (STZ)-Induced Diabetic Nephropathy in Rats via NRF2/ HO-1 Mediated Pathways 2020;11:1119.
• 12. Altındağ F, Rağbetli MÇ, Özdek U, Koyun N, Ismael Alhalboosi JK, Elasan S. Combined treatment of sinapic acid and ellagic acid attenuates hyperglycemia in streptozotocininduced diabetic rats. Food and Chemical Toxicology 2021;156:112443.
• 13. Uzar E, Alp H, Cevik MU, Fırat U, Evliyaoglu O, Tufek A, Altun Y. Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurological Sciences 2012;33:567–574.
• 14. Shahmohamady P, Eidi A, Mortazavi P, Panahi N, Minai- Tehrani D. Effect of sinapic acid on memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats. Polish Journal of Pathology 2018;69(3):266–266.
• 15. Lyoussi B, Bakour M, El Menyiy N, El Ghouizi A. Hypoglycemic, hypolipidemic and hepato-protective effect of bee bread in streptozotocin-induced diabetic rats. Avicenna Journal of Phytomedicine 2021;11(4):343–352.
• 16. Arya A, Al-Obaidi MMJ, Shahid, N, Noordin MIB, Looi CY, Wong WF, Khaing SL, Mustafa MR. Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: a mechanistic study. Food and Chemical Toxicology 2014;71:183–196.
• 17. Nithya R, Subramanian S. Antioxidant properties of sinapic acid: In vitro and in vivo approach. Asian Journal of Pharmaceutical and Clinical Research 2017;10(6):255–255.
• 18. Hussein J, El Naggar ME, Latif YA, Medhat D, El Bana M, Refaat E, Morsy S. Solvent-free and one pot synthesis of silver and zinc nanoparticles: Activity toward cell membrane component and insulin signaling pathway in experimental diabetes. Colloids Surf B Biointerfaces 2018;170:76–84.
• 19. Yang DK, Kang HS. Anti-Diabetic Effect of Cotreatment with Quercetin and Resveratrol in Streptozotocin-Induced Diabetic Rats. Biomol Ther 2018;26(2):130–138.
• 20. Pandi A, Kalappan VM. Pharmacological and therapeutic applications of Sinapic acid—an updated review. Molecular Biology Reports 2021;48:3733–3745.
• 21. Al-Baqami NM, Hamza RZ. Protective Effect of Resveratrol against Hepatotoxicity of Cadmium in Male Rats: Antioxidant and Histopathological Approaches. Coatings 2021;11:594–604.
• 22. Bento-Silva A, Koistinen VM, Mena P, Bronze MR, Hanhineva K, Sahlstrøm S, Kitrytė V, Moco S, Aura AM. Factors affecting intake, metabolism and health benefits of phenolic acids: do we understand individual variability? European Journal of Nutrition 2020:59(4):1275–1293.
• 23. Raish M, Ahmad A, Ansari MA, Alkharfy KM, Ahad A, Al- Jenoobi FI, Al-Mohizea A M, Khan A, Ali N. Effects of sinapic acid on hepatic cytochrome P450 3A2, 2C11, and intestinal P-glycoprotein on the pharmacokinetics of oral carbamazepine in rats: Potential food/herb-drug interaction. Epilepsy Research 2019;153:14–18.
• 24. Torbenson M, Washington K. Pathology of liver disease: advances in the last 50 years. Human Pathology 2020;95:78– 98.
• 25. Ghara AR, Ghadi FE, Hosseini SH, Piacente S, Cerulli A, Alizadeh A, Mirmahmoudi R. Antioxidant and Antidiabetic Effect of Capparis decidua Edgew (Forssk.)Extract on Liver and Pancreas of Streptozotocin-Induced Diabetic Rats. J Appl Biotechnol Rep 2021;8(1):76–82.
• 26. Bilal M, Iqbal MS, Shah SB, Rasheed T, Iqbal H. Diabetic complications and insight into antidiabetic potentialities of ethno-medicinal plants: a review. Recent Patents on Inflammation & Allergy Drug Discovery 2018;12(1):7–23.
• 27. Chandrasekara A, Shahidi F. Herbal beverages: Bioactive compounds and their role in disease risk reduction-A review. Journal of Traditional and Complementary Medicine 2018;8(4):451–458.
• 28. Brea R, Motiño O, Francés D, García-Monzón C, Vargas J, Fernández-Velasco M, Boscá L, Casado M, Martín-Sanz P, Agra N. PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a- 5p and miR-28a-5p, Biochimica et Biophysica Acta (BBA)- Molecular Basis of Disease 2018;1864:325–337.
• 29. Zhao Y, Chen SJ, Wang JC, Niu HX, Jia QQ, Chen XW, Du XY, Lu L, Huang B, Zhang Q, Chen Y, Long HB. Sesquiterpene Lactones Inhibit Advanced Oxidation Protein Product- Induced MCP-1 Expression in Podocytes via an IKK/NF-κBDependent Mechanism 2015;2015:934058.
• 30. Wang W, Wang C, Din, XQ, Pan Y, Gu TT, Wang MX, Liu YL, Wang FM, Wang, SJ, Kong LD. Quercetin and allopurinol reduce liver thioredoxin-interacting protein to alleviate inflammation and lipid accumulation in diabetic rats. British Journal of Pharmacology 2013;169(6):1352–1371.
• 31. Chang CC, Chang C Y, Huang JP, Hung LM. Effect of Resveratrol on Oxidative and Inflammatory Stress in Liver and Spleen of Streptozotocin-Induced Type 1 Diabetic Rats. Chinese Journal of Physiology 2012;55.