Effectiveness of Hesperidin on Methotrexate-Induced Testicular Toxicity in Rats

Bu çalışmanın amacı, metoraksat (MTX) uygulanan ratlarda hesperidinin erkek üreme sistemi üzerindeki etkisini araştırmaktı. Çalışmada 8 haftalık yaşta, 250-300 g canlı ağırlığa sahip 28 erkek Wistar albino cinsi rat kullanıldı. Dört deney grubu oluşturuldu; Grup 1 (n=7): kontrol grubu, sadece yem ve su verildi. Grup 2 (n=7): MTX grubu, 20 mg/kg MTX i.p. tek doz uygulandı. Grup 3 (n=7): Hesperidin grubu, 200 mg/kg hesperidin 7 gün süre ile ağızdan sonda yardımıyla verildi. Grup 4 (n=7): MTX + hesperidin grubu, 20 mg/kg MTX i.p tek doz uygulamasını takiben 200 mg/kg hesperidin 7 gün süre ile ağızdan sonda yardımıyla verildi. Deney sonunda ratlar dekapite edilerek biyokimyasal, histopatolojik ve spermatolojik parametreler incelendi. MTX grubunda sperm motilitesi ve yoğunluğunun, CAT, GPx ve SOD enzimlerinin ve GSH düzeyinin düştüğü, TNF-alpha ve IL-1 Beta ile MDA düzeyinin arttığı, spermatojenik hücrelerin düzenli yapısının bozulduğu, seminifer tubullerin nekrotik ve dejeneratif bir hal aldığı gözlendi. MTX + hesperidin uygulaması ile spermatolojik parametrelerin düzeldiği, nekrotik ve dejeneratif değişikliklerin azaldığı tespit edildi. Bu sonuçlar hesperidinin rat testislerinde MTX tarafından oluşan yıkıcı etkiler üzerinde koruyucu etkiye sahip olduğunu gösterdi

Ratlarda Metoraksat Kaynaklı Testiküler Toksisite Üzerine Hesperidinin Etkisi

The aim of this study was to investigate the effect of hesperidin on male reproductive system in rats to which methotrexate (MTX) was administered. In the study, 28 male Wistar albino rats at the age of 8 weeks and had 250-300 g of live weight were used. Four experimental groups were formed; Group 1 (n=7): The control group, only feed and water were given. Group 2 (n=7): MTX group, a single dose of 20 mg/kg of i.p. MTX was administered. Group 3 (n=7): Hesperidin group, 200 mg/kg of hesperidin was administered by gavage for 7 days. Group 4: MTX + hesperidin group (n=7): Following administration of a single dose of 20 mg/kg i.p. MTX , 200 mg/kg of Hesperidin was administered by oral gavage for 7 days. At the end of the experiment, rats were decapitated and biochemical, histopathological and spermatological parameters were examined. It was observed that in the MTX group, sperm motility and density, the enzymes CAT, GPx and SOD and GSH level decreased, TNF-alpha and IL-1 Beta, as well as MDA, levels were increased, regular structure of spermatogenic cells was impaired, and seminiferous tubules became necrotic and degenerative. It was determined that spermatological parameters improved and, necrotic and degenerative changes diminished by the administration of MTX+hesperidin. These outcomes indicated that hesperidin had a protective effect on destructive effects of MTX in rat testiclesv

___

  • 1. Kim J, Kim K, Chung M: Testicular cytotoxicity of DA- 125, a new anthracycline anticancer agent, in rats. Reprod Toxicol, 13, 391-397, 1999. DOI: 10.1016/S0890-6238(99)00028-3
  • 2. Bayram M, Ozogul C, Dursun A, Ercan ZS, Isik I, Dilekoz E: Light and electron microscope examination of the effects of methotrexate on the endosalpinx. Eur J Obstet Gynecol Reprod Biol, 120, 96-103, 2005. DOI: 10.1016/j.ejogrb.2004.08.014
  • 3. Naziroglu M: Enhanced testicular antioxidant capacity in streptozotocininduced diabetic rats: Protective role of vitamins C and E and selenium. Biol Trace Elem Res, 94, 61-72, 2003. DOI: 10.1385/BTER:94:1:61
  • 4. Sikka SC: Oxidative stress and role of antioxidants in normal and abnormal sperm function. Front Biosci, 1, 78-86, 1996.
  • 5. Uzar E, Sahin O, Koyuncuoglu HR, Uz E, Bas O, Kilbas S, Yilmaz H, Yurekli VA, Kucuker H, Songur A: The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: Protective effect of caffeic acid phenethyl ester. Toxicology, 218, 125- 133, 2006. DOI: 10.1016/j.tox.2005.10.014
  • 6. Jahovic N, Sener G, Cevik H, Ersoy Y, Arbak S, Yeğern BC: Amelioration of methotrexate-induced enteritis by melatonin in rats. Cell Biochem Funct, 22, 169-178, 2004. DOI: 10.1002/cbf.1071
  • 7. Nouri HS, Azarmi Y, Movahedin M: Effect of growth hormone on testicular dysfunction induced by methotrexate in rats. Andrologia, 41, 105-110, 2009. DOI: 10.1111/j.1439-0272.2008.00897.x
  • 8. Gökce A, Oktar S, Koc A, Yonden Z: Protective effects of thymoquinone against methotrexate-induced testicular injury . Hum Exp Toxicol, 30, 897- 903, 2011. DOI: 10.1177/0960327110382564
  • 9. Şener G, Demiralp EE, Çetiner M, Ercan F, Yeğen BÇ: B-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects. Eur J Pharmacol, 542, 170-178, 2006. DOI: 10.1016/j.ejphar.2006.02.056
  • 10. Vardi N, Parlakpinar H, Ates B, Cetin A, Otlu A: Antiapoptotic and antioxidant effects of B-carotene against methotrexate- induced testicular injury. Fertil Steril, 92, 2028-2033, 2009. DOI: 10.1016/j. fertnstert.2008.09.015
  • 11. Gil-Izquierdo A, Gil MI, Ferreres F, Tomas-Barberan FA: In vitro availability of flavonoids and other phenolics in orange juice. J Agric Food Chem, 49, 1035-1041, 2001. DOI: DOI: 10.1021/jf0000528
  • 12. Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA: Potential protective effects of quercetin and curcumin on paracetamol- induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol, 48, 3246-3261, 2010. DOI: 10.1016/j.fct.2010.08.034
  • 13. Dimpfel W: Different anticonvulsive effects of hesperidin and its aglycone hesperetin on electrical activity in the rat hippocampus in-vitro. J Pharm Pharmacol, 58, 375-379, 2006. DOI: 10.1211/jpp.58.3.0012
  • 14. Arafa HMM, Aly HAA, Abd-Ellah MF, El-Refaey HM: Hesperidin attenuates benzo[α] pyrene-induced testicular toxicity in rats via regulation of oxidant/antioxidant balance. Toxicol Ind Health, 25, 417- 427, 2009. DOI: 10.1177/0748233709106624
  • 15. Meiyanto E, Hermawan A, Anindyajati A: Natural products for cancer-targeted therapy: Citrus flavonoids as potent chemopreventive agents. Asian Pac J Cancer Prev, 13, 427-436, 2012.
  • 16. Tanaka T, Tanaka T, Tanaka M, Kuno T: Cancer chemoprevention by citru pulp and juices containing high amounts of ß-cryptoxanthin and hesperidin. J Biomed Biotechnol, 2012 (2012): Article ID: 516981, 2012. DOI: 10.1155/2012/516981
  • 17. Kaya K, Ciftci O, Cetin A, Dogan H, Basak N: Hesperidin protects testicular and spermatological damages induced by cisplatin in rats. Andrologia, 47, 793-800, 2015. DOI: 10.1111/and.12332
  • 18. Padmanabhan S, Tripathi DN, Vikram A, Ramarao P, Jena GB. Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: Intervention of folic and folinic acid. Mutat Res, 673, 43-52, 2009. DOI: 10.1016/j.mrgentox.2008.11.011
  • 19. Uzar E, Koyuncuoglu HR, Uz E, Yılmaz HR, Kutluhan S, Kilbas S, Gultekin F: The activities of antioxidant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: Protective effect of caffeic acid phenethyl ester. Mol Cell Biochem, 291, 63- 68, 2006. DOI: 10.1007/s11010-006-9196-5
  • 20. Johnsen SG: Testicular biopsy score count - A method for registration of spermatogenesis in human testicles. Normal values and results of 335 hypogonadal males. Hormones, 1, 2-25, 1970. DOI: 10.1159/000178170
  • 21. Sonmez M, Turk G, Yuce A: The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats. Theriogenology, 63, 2063-2072, 2005. DOI: 10.1016/j.theriogenology. 2004.10.003
  • 22. Turk G, Atessahin A, Sonmez M, Ceribasi AO, Yuce A: Improvement of cisplatin-induced injuries to sperm quality, the oxidant–antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril, 89, 1474-1481, 2008. DOI: 10.1016/j.fertnstert.2007.04.059
  • 23. Placer ZA, Cushman LL, Johnson BC: Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem, 16, 359-364, 1966. DOI: 10.1016/0003-2697(66)90167-9
  • 24. Sedlak J, Lindsay RH: Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem, 25, 192-205, 1968. DOI: 10.1016/0003-2697(68)90092-4
  • 25. Sun Y, Oberley LW, Li Y: A simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497-500, 1988.
  • 26. Matkovics B, Szabo L, Varga IS: Determination of enzyme activities in lipid peroxidation and glutathione pathways. Lab Diagn, 15, 248-249, 1988.
  • 27. Aebi H: Catalase. In, Bergmeyer HU (Ed): Methods in Enzymatic Analysis. 276-286, Academic Press, New York, 1983.
  • 28. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ: Protein measurements with the folin phenol reagent. J Biol Chem, 193, 265-275, 1951.
  • 29. Drasga RE, Einhorn LH, Williams SD, Patel DN, Stevens EE: Fertility after chemotherapy for testicular cancer. J Clin Oncol, 1, 179-183, 1983. DOI: 10.1200/JCO.1983.1.3.179
  • 30. Chandra AK, Chatterjee A, Ghosh R, Sarkar M: Vitamin Esupplementation protect chromium (VI)-induced spermatogenic and steroidogenic disorders in testicular tissues of rats. Food Chem Toxicol, 48, 972-979, 2010. DOI: 10.1016/j.fct.2010.01.008
  • 31. Padmanabhan S, Tripathi DN, Vikram A, Ramarao P, Jena GB: Cytotoxic and genotoxic effects of methotrexate in germ cells of male Swiss mice. Mutat Res, 655(1-2), 59-67, 2008. DOI: 10.1016/j.mrgentox. 2008.07.003
  • 32. Aksu EH, Akman O, Özkaraca M, Ömür AD, Uçar Ö: Effect of maclura pomifera extract on cisplatin-induced damages in reproductive system of male rats. Kafkas Univ Vet Fak Derg, 21, 397-403, 2015. DOI: 10.9775/kvfd.2014.12662
  • 33. Ateşşahin A, Karahan İ, Türk G, Gür S, Yılmaz S, Çeribaşı AO: Protective role of lycopene on cisplatin-induced changes in sperm characteristics, testicular damage and oxidative stress in rats. Reprod Toxicol, 21, 42-47, 2006. DOI: 10.1016/j.reprotox.2005.05.003
  • 34. Salem EA, Salem NA, Maarouf AM, Serefoglu EC, Hellstrom WJG: Selenium and lycopene attenuate cisplatin-induced testicular toxicity associated with oxidative stress in Wistar rats. Urology, 79, 1184.e1-1184. e6, 2012. DOI: 10.1016/j.urology.2011.12.006
  • 35. Armagan A, Uzar E, Uz E, Yılmaz HR, Kutluhan S: Caffeic acid phenethyl ester modulates methotrexate-induced oxidative stress in testicles of rat. Hum Exp Toxicol, 27, 547- 552, 2008. DOI: 10.1177/ 0960327108092293
  • 36. Shagirtha K, Pari L: Hesperetin, a citrus flavonone, protects potentially cadmium induced oxidative testicular dysfunction in rats. Ecotoxicol Environ Saf, 74, 2105-2111, 2011. DOI: 10.1016/j.ecoenv.2011.06.002
  • 37. Amin A, Abraham C, Hamza A, Abdalla ZA, Al-Shamsi SB, Harethi SS, Daoud S: A standardized extract of Ginkgo biloba neutralizes cisplatin-mediated reproductive toxicity in rats. J Biomed Biotechnol, 2012, 362049, 2012. DOI: 10.1155/2012/362049
  • 38. Riccioli A, Starace D, D’Alessio A, Starace G, Padula F, De Cesaris P, Filippini A, Ziparo E: TNF-alpha and IFN-gamma regulate expression and function of the Fas system in the seminiferous epithelium. J Immunol,165, 743-749, 2000. DOI: 10.4049/jimmunol.165.2.743
  • 39. Zarpelon AC, Rodrigues FC, Lopes AH, Souza GR, Carvalho TT, Pinto LG, Xu D, Ferreira SH, Alves-Filho JC, McInnes IB: Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain. FASEB J, 30, 54-65, 2016. DOI: 10.1096/fj.14-267146
  • 40. Georgy GS, Maher OW: Ellagic acid and rosmarinic acid attenuate doxorubicin-induced testicular injury in rats. J Biochem Mol Toxicol, 2017 (in Press). DOI: 10.1002/jbt.21937
  • 41. Sherif IO, Abdel-Aziz A, Sarhan OM: Cisplatin-induced testicular toxicity in rats: The protective effect of arjunolic acid. J Biochem Mol Toxicol, 28, 515-521, 2014. DOI: 10.1002/jbt.21593
  • 42. Alyoussef A, Al-Gayyar MM: Thymoquinone ameliorates testicular tissue inflammation induced by chronic administration of oral sodium nitrite. Andrologia, 48, 501-508, 2016. DOI: 10.1111/and.12469
  • 43. Valavanidis A, Vlachogianni T, Fiotakis C: 8-hydroxy-2′- deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 27, 120-139, 2009. DOI: 10.1080/10590500902885684
  • 44. Akman O, Şengül E, Özkanlar S, Can S, Koç A, Karadeniz A, Şimşek N: The melatonin attenuates alloxan induced post-diabetic testicular damage and oxidative effects in rats. Kafkas Univ Vet Fak Derg, 21, 719- 728, 2015. DOI: 10.9775/kvfd.2015.13249
  • 45. Tugcu V, Gedikbasi A, Mutlu B, Guner E, Uhri M, AndicanG, Ozbek E, Tasci AI: Increased testicular 8-hydroxy-20-deoxyguanosine (8-OHdG) and inducible nitric oxide synthetase (iNOS) and nuclear factor jB (NF-jB) expressions in experimental rat varicocele. Arch Ital Urol Androl, 82, 148- 153, 2010.
  • 46. Shen YC, Yen JC, Liou KT: Ameliorative effects of caffeic acid phenethyl ester on an eccentric exercise-induced skeletal muscle injury by down-regulating NF-jB mediated inflammation. Pharmacology, 91, 219-228, 2013. DOI: 10.1159/000348412
  • 47. Amin A, Abraham C, Hamza AA, Abdalla ZA, Al-Shamsi SB, Harethi SS, Daoud S: A standardized extract of Ginkgo biloba neutralizes cisplatin-mediated reproductive toxicity in rats. J Biomed Biotechnol, 2012. DOI: 10.1155/2012/362049
  • 48. Şimşek N, Koç A, Karadeniz A, Yıldırım ME, Çelik HT, Sarı E, Kara A: Ameliorative effect of selenium in cisplatin-induced testicular damage in rats. Acta Histochemica, 118, 263-270, 2016. DOI: 10.1016/j. acthis.2016.02.002
Kafkas Üniversitesi Veteriner Fakültesi Dergisi-Cover
  • ISSN: 1300-6045
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1995
  • Yayıncı: Kafkas Üniv. Veteriner Fak.
Sayıdaki Diğer Makaleler

The Assessment of Diagnostic and Ultrasonographic Findings in a Bitch with True Vaginal Prolapse

Isfendiyar DARBAZ, Osman ERGENE, ESRA CANOOĞLU, Çağrı GÜLTEKİN, Selim ASLAN

Milk Production, Body Condition Score and Metabolic Parameters at the Peak of Lactation as Risk Factors for Chronic Lameness in Dairy Cows

Mimi RISTEVSKI, Bojan TOHOLJ, Marko CINCOVI?, Plamen TROJA?ANEC, Jo?e STARI?, Ozren SMOLEC

A Study on Observation of Respiratory Ultrasound Plethysmography in Donkeys

Osman GÜNGÖR, René VAN DEN HOVEN

Surgical Treatment Results of Young and Adult Cats with Pectus Excavatum

KÜRŞAT ÖZER, MURAT KARABAĞLI, Özgür AKGÜL, YALÇIN DEVECİOĞLU, Alper DEMİRUTKU

Antitumorigenic Activity of the Herbal Mixture-AK27 on Ehrlich Ascites Carcinoma in Mice

İBRAHİM DEMİRKAN, TOLGA ERTEKİN, MUSA KORKMAZ, İBRAHİM KILIÇ, AYSUN ÇEVİK DEMİRKAN, MEHMET FATİH BOZKURT, Ahmet KONUKTÜRK

Pathological Examination of Deep Pectoral Myopathy in House Reared Broilers

ÖZLEM ÖZMEN

Effects of Birth Type on Growth, Fattening Performance and Carcass Characteristics in Honamlı Male Kids

ÖZKAN ELMAZ, AYKUT ASIM AKBAŞ, MUSTAFA SAATCI

Soluble Expression, Protein Purification and Quality Control of Recombinant Porcine Interferon-α

Jun ZHAO, Hai-yang YU, Lin GAN, Yu ZHAO, Shu-qi LI, Xiu-le FU, Ming-li WANG, Jason CHEN

The Prevalence and Associated Risk Factors of Coa Gene (Coagulase Positive Staphylococcus aureus) from Bovine Milk

Muhammad Abdul Rauf MALIK, Muhammad IJAZ, Amjad Islam AQIB, Shahid Hussain FAROOQI, Kashif HUSSAIN

Caecal Bacterial Populations and Growth of Broiler Chickens Fed Diets with Different Particle Sizes and Forms

Mohsen GHASEMINEJAD, Ali Asghar SADEGHI, Farahnaz MOTAMEDI-SEDEH, Mohammad CHAMANI