Bengü Gülhan AYDIN, Özcan PİŞKİN, Yılmaz BAŞ, Kemal KARAKAYA, Özlem ELMAS, Murat CAN, Çağatay BÜYÜKUYSAL

Hesperidinin iyonlaştırıcı radyasyonun neden olduğu karaciğer hasarı üzerine koruyucu etkileri

Amaç Karaciğer çoğunlukla üst batın, sağ alt akciğer, distal özafagus tümörleri için veya tüm vücut radyoterapi (RT) uygulamasında radyasyona maruz kalmaktadır. Bu çalışmada iyonizan radyasyonun karaciğer dokusunda neden olduğu oksidatif stresi üzerine hesperidinin koruyucu etkisinin araştırılması amaçlanmıştır. Gereç ve Yöntemler 24 yetişkin erkek rat rastgele 4 gruba ayrıldı. Kontrol grubuna sadece fizyolojik salin, Grup HES’e 15 gün 50 mg/kg hesperidin, Grup RAD’a sadece irradyasyon yapıldı ve Grup HES + RAD’a 15 gün boyunca 50 mg/kg hesperidin verildi, 15. gün sonunda abdominopelvik bölgeye 10 Gy dozunda radyasyon uygulandı. Radyasyon uygulandıktan 24 saat sonra Total antioksidan kapasite (TAK) ve malondialdehid (MDA) tayini için karaciğer ve kan örnekleri alındı ve ayrıca histopatolojik inceleme yapıldı. Bulgular Grup RAD ile karşılaştırıldığında, plazma ve doku MAD düzeyi Grup HES + RAD'da anlamlı olarak azaldı (p=0.002). Hem plazma hem de dokudaki TAK, HES + RAD grubunda anlamlı olarak daha yüksek bulundu (sırasıyla, p = 0.002, p = 0.004).Grup RAD’da , histolojik olarak portal alanda ödem, sinüzoitlerde dilatasyon, hepatositlerde belirgin olarak şime, intrasitoplazmik vakuolizasyon ,arada nekroz, belirgin sinüzoidal dilatasyon, santral ven dilatasyonu ve konjesyon izlendi. Nükleer hipertrofi belirgindi. Grup HES+RAD, Grup RAD ile karşılaştırıldığında periportal ödem, santral ven dilatasyonu ve konjesyon histolojik olarak belirgin değildi Sonuç Radyoterapinin lipit peroksidasyonunda artışa ve antioksidan kapasitede azalmaya neden olduğu; Ratlarda 15 gün boyunca 50 mg/kg/gün hesperidin uygulamasının, radyasyonun neden olduğu karaciğer hasarında görülen histolojik değişiklikleri ve oksidatif stresi azalttığı görülmüştür.

Anahtar Kelimeler:

Hesperidin, karaciğer hasarı, oksidatif stres

Protective effects of hesperidin on ionizing radiation-induced liver damage

Aim: Liver is mostly exposed to radiation during radiotherapy to the upper abdomen, the right lobe of the lung, distal esophagus tumors or total body irradiation. Radiation may lead to cellular damage, and clinical and laboratory findings of liver dysfunction. This study aimed to investigate the protective effect of peroral hesperidin on reducing oxidative stress in liver tissue caused by ionızing radiation Material and Methods: 24 adult male rats were randomly divide into four groups. Group control was given only physiological saline, Group HES was given hesperidin at 50 mg/kg body weight (BW) for 15 days, Group RAD was given only irradiation, and Group HES+RAD was given hesperidin at 50 mg/kg BW daily and then irradiated. At the end of 15 hesperidinin days, the animals in Groups RAD and HES+RAD were exposed to a dose of 10 Gy to the abdominopelvic region. Liver and blood samples were used for determination of total antioxidant status (TAS) and malondialdehyde (MDA) and also histopathological examination was performed.Results: Compared with the Group RAD, the plasma and tissue MAD level was significantly decreased in Group HES+RAD (p=0.002). Both plasma and tissue levels of TAS was found significantly higher in HES+RAD group (respectively, p=0.002,p=0.004). Histological examination of Group RAD, portal edema, significant intra-cytoplasmic vacuolization, swelling in the hepatocytes, necrosis, significant sinusoidal and central vein dilation and congestion were observed . In group HES+RAD periportal edema, central vein dilation and congestion were not histologically evident when compared with Group RAD. Conclusion: Radiotherapy was found to lead to an increase in lipid peroxidation and a reduction in anti-oxidant capacity; 50 mg/kg/day hesperidin administration for 15 consecutive days was seen to reduce the histological changes of liver damage and oxidative stress in rats

Keywords:

Hesperidin liver damage, oxidative stress, radiation,

PDF

___

1. Gupta RK, Patel AK, Shah N, et al. Oxidative stress and antioxidants in disease and cancer: a review. Asian Pac J Cancer Prev 2014; 15: 4405-09.
2. Azzam EI, Jay-Gerin JP, Pain D. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett 2012; 327: 48-60.
3. Sabitha KE, Shyamaladevi CS. Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. Oral Oncol 1999; 35: 272-77.
4. The Sakhi AK, Russnes KM, Thoresen M, et al. Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study. BMC Cancer 2009; 9: 458-62.
5. Maher KE. Radiation therapy: Toxicities and management. Yarbro, CH, Frogge MH, Goodman M, editors. Cancer Nursing: Principles and Practice. Jones and Bartlett Publishers; 2005.p.283-314.
6. Liang SX, Zhu XD, Xu ZY et al. Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: The risk factors and hepatic radiation tolerance. Int J Radiat Oncol Biol Phys 2006; 65: 426-34.
7. Pan CC, Kavanagh BD, Dawson LA et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 2010; 76: 94-100.
8. Van Acker, F.A., Schouten, O., Haenen, R.M., van der Vijh,W.J.F., Bast, A. Flavanoid can replace tocopherol as an antioxidant. FEBS Lett 2000; 473, 145–48.
9. E. J. Middleton. Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol 1998; 439: 175-82.
10. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal 2013; 2013: 162750.
11. Banjarnahor SDS, Artanti N. Antioxidant properties of flavonoids. Med J Indones 2014; 23: 239-44.
12. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010; 4: 118–26.
13. Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of Citrus Flavonoids, Naringin and Naringenin, on Metabolic Syndrome and Their Mechanisms of Action. Adv Nutr 2014; 5: 404–17.
14. Suarez J, Herrera MD., Marhuenda, E. Invitro scavenger and antioxidant properties of hesperidin and neohesperidin dihydrochalcone. Phytomedicine 1998; 5: 469-73.
15. Gracy RW, Talent JM, Kong Y, Conrad CC. Reactive oxygen species: the unavoidable environmental insult? Mutat Res1999; 428: 17-22.
16. Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP. Influence of ferulic acid on γ-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes. Toxicology 2006; 228: 249–58.
17. Chitra S, Shyamala Devi CS. Effect of alpha-tocopherol on pro-oxidant and antioxidant enzyme status in radiation-treated oral squamous cell carcinoma. Indian J Med Sci 2008; 62: 141-48.
18. Garg A, Garg S, Zaneveld LJ, Singla AK. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother Res 2001; 15: 655-69.
19. Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco 2001; 56: 683-87.
20. Chen YT, Zheng RL, Jia ZJ, Ju Y. Flavonoids as superoxide scavengers and antioxidants. Free Radic Biol Med 1990; 9: 19-21.
21. Rezaeyan A, Fardid R, Haddadi GH et al. Evaluating Radioprotective Effect of Hesperidin on Acute Radiation Damage in the Lung Tissue of Rats. J Biomed Phys Eng 2016; 6: 165–74.
22. Shaban NZ, Ahmed Zahran AM, El-Rashidy FH, Abdo Kodous A. Protective role of hesperidin against γ-radiation-induced oxidative stress and apoptosis in rat testis. J Biol Res 2017; 24:5.
23. Pradeep K, Park SH, Ko KC. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats. Eur J Pharmacol 2008; 587: 273-80.
24. Pan CC, Kavanagh BD, Dawson LA et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 2010; 76: 94-100.
25. Kalpana KB, Devipriya N, Srinivasan M, Vishwanathan P, Thayalan K, Menon VP. Evaluating the radioprotective effect of hesperidin in the liver of Swiss albino mice. Eur J Pharmacol 2011; 658: 206-12.
26. Kim J, Jung Y. Radiation-induced liver disease: current understanding and future perspectives Exp Mol Med 2017; 49: 359.
27. Elshazly SM, Mahmoud AA. Antifibrotic activity of hesperidin against dimethylnitrosamine-induced liver fibrosis in rats, Naunyn Schmiedeberg's Arch. Pharmacol 2014; 387: 559–67.