Resveratrol treatment reduces apoptosis and morphological alterations in cisplatin induced testis damage

Resveratrol treatment reduces apoptosis and morphological alterations in cisplatin induced testis damage

Cisplatin commonly used as a chemotheropotic agent however, it is associated with numerous side effects such as reproductive cytotoxicity. It causes spermatogenic cell death and DNA damage in spermatozoa via the formation of reactive oxygene species. Resveratrol (3,5,4'-trans-trihydroxystilbene), a natural phytoalexin, is a potent antioxidant agent, present in a wide variety of dietary sources including grapes, plums and peanuts. The aim of present study to evaluate the beneficial effects of resveratrol on cisplatin induced testis damage. Male Sprague Dawley rats were used in the study and four experimental groups were formed as: 1- saline applied control, 2- resveratrol applied control, 3- cisplatin and 4- cisplatin+resveratrol groups. Following a single dose of cisplatin (7 mg/kg i.p.), either saline or resveratrol (10 mg/kg, orally) was administered for 5 days. Testis samples were prepared for histopathological and ultrastructural evaluations, cell proliferation and apoptosis. Tissue malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined biochemically. Degenerated and atrophic tubules of tissue, apoptotic cells, MDA level and MPO activity were increased although proliferation index and GSH level were decreased in cisplatin group. Degenerated tight junctions between the Sertoli cells and vacuole formation in germinal epithelial cells were also revealed at this group. However, resveratrol treatment reduced degenerated and atrophic tubules, apoptotic cells, vacuole formation in germinal epithelial cells, MDA level and MPO activity and increased proliferation index and GSH level in testis. These results showed that resveratrol ameliorates cisplatin induced testis injury by the impairment of oxidative stress and apoptosis

___

  • Sherif IO, Abdel-Aziz A, Sarhan OM. Cisplatin-induced testicular toxicity in rats: the protective effect of arjunolic acid. J Biochem Mol Toxicol. 2014; 28(11): 515-521. [CrossRef
  • Chinwe GS, Azuka OI, Adaeze NC. Resveratrol supplementation rescues pool of growing follicles and ovarian stroma from Cisplatin-induced toxicity on the ovary in Sprague-Dawley rats: An experimental study. Int J Reprod Biomed. 2018; 16(1): 19-30. [CrossRef]
  • Chiang KC, Tsui KH, Chung LC, Yeh CN, Feng TH, Chen WT, Chang PL, Chiang HY, Juang HH. Cisplatin modulates B cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53independent pathways. Sci Rep. 2014; 4: 5511. [CrossRef]
  • Khaled HM, Shafik HE, Zabhloul MS, Ghoneim M, Saber RA, Manie M, Enein HA, Megeed HA, Mansur O, Sherbini ME, Mahran TZ, Kalawee ME, Badran A, Ramadan SM. Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive transitional and squamous cell carcinoma of the bladder: Effect on survival and bladder preservation. Clin Genitourin Cancer. 2014; 12(5): e233-40. [CrossRef]
  • Groh T, Hrabeta J, Khalil MA, Doktorova H, Eckschlager T, Stiborova M. The synergistic effects of DNA-damaging drugs cisplatin and etoposide witha histone deacetylase inhibitor valproate in high-risk neuroblastoma cells. Int J Oncol. 2015; 47(1): 343-352. [CrossRef]
  • Kim MJ, Kim SM, Jung HA, Hong JY, Chang WJ, Choi MK, Kim HS, Sun JM, Park K, Ahn MJ. Efficacy and safety of cisplatin and weekly docetaxel in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Korean J Intern Med. 2018; Epub a head of print. [CrossRef]
  • Şener G, Satiroglu H, Kabasakal L, Arbak S, Oner S, Ercan F, Keyer-Uysal M. The protective effect of melatonin on cisplatin nephrotoxicity. Fundam Clin Pharmacol. 2000; 14(6): 553-560. [CrossRef]
  • Kim SJ, Park C, Lee JN, Park R. Protective roles of fenofibrate against cisplatin induced ototoxicity by the rescue of peroxisomaland mitochondrial dysfunction. Toxicol Appl Pharmacol. 2018; 353: 43-54. [CrossRef]
  • Li DW, Sun JY, Wang K, Zhang S, Hou YJ, Yang MF, Fu XY, Zhang ZY, Mao LL, Yuan H, Fang J, Fan CD, Zhu MJ, Sun BL. Attenuation of cisplatin-ınduced neurotoxicity by Cyanidin, a natural ınhibitor of ROS-mediated apoptosis in PC12 Cells. Cell Mol Neurobiol. 2015; 35(7): 995-1001. [CrossRef]
  • Patanè S. Cardiotoxicity: cisplatin and long-term cancer survivors. Int J Cardiol. 2014; 175(1): 201-202. [CrossRef]
  • Liu M, Maselli J, Hales BF, Robaire B. The effects of chemotherapy with bleomycin, etoposide, and cis-platinum on telomeres in rat male germ cells. Andrology. 2015; 3(6): 1104-1112. [CrossRef]
  • Marcon L, Hales BF, Robaire B. Reversibility of the effects of subchronic exposure to the cancer chemotherapeutics bleomycin, etoposide, and cisplatin on spermatogenesis, fertility, and progeny outcome in the male rat. J Androl. 2008; 29(4): 408-417. [CrossRef]
  • Türk G, Ceribaşı AO, Sahna E, Ateşşahin A. Lycopene and ellagic acid prevent testicular apoptosis induced by cisplatin. Phytomedicine. 2011; 18(5): 356-361. [CrossRef]
  • Tian M, Liu F, Liu H, Zhang Q, Li L, Hou X, Zhao J, Li S, Chang X, Sun Y. Grape seed procyanidins extract attenuates Cisplatin-induced oxidative stress and testosterone synthase inhibition in rat testes. Syst Biol Reprod Med. 2018; 64(4): 246-259. [CrossRef]
  • Madhu P, Reddy KP, Reddy PS. Melatonin reduces oxidative stress and restores mitochondrial function in the liver of rats exposed to chemotherapeutics. J Exp Zool A Ecol Genet Physiol. 2015; 323(5): 301-308. [CrossRef]
  • Sanchez-Gonzalez PD, Lopez-Hernandez FJ, Duenas M, Prieto M, Sanchez-Lopez E, Thomale J, Ruiz-Ortega M, Lopez-Novoa JM, Morales AI. Differential effect of quercetin on cisplatin-induced toxicity in kidney and tumor tissues. Food Chem Toxicol. 2017; 107(Pt A): 226-236. [CrossRef]
  • Gusman J, Malonne H, Atassi G. A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis. 2001; 22(8): 1111-1117.[CrossRef]
  • Tatlidede E, Sehirli O, Velioğlu-Oğünc A, Cetinel S, Yeğen BC, Yarat A, Süleymanoğlu S, Sener G. Resveratrol treatment protects against doxorubicin-induced cardiotoxicity by alleviating oxidative damage. Free Radic Res. 2009; 43(3): 195-205. [CrossRef]
  • Sener G, Topaloğlu N, Sehirli AO, Ercan F, Gedik N. Resveratrol alleviates bleomycin-induced lung injury in rats. Pulm Pharmacol Ther. 2007; 20(6): 642-649.[CrossRef]
  • Heeba GH, Hamza AA, Hassanin SO. Induction of heme oxygenase-1 with hemin alleviates cisplatin-induced reproductive toxicity in male rats and enhances its cytotoxicity in prostate cancer cell line. Toxicol Lett. 2016; 264: 3850.[CrossRef]
  • Coşkun N, Hatipoğlu MT, Ozoğul C, Korkmaz C, Akyol SN, Mıcılı SC, Arık GS, Erdoğan D. The protective effects of acetyl L-carnitine on testis gonadotoxicity induced by cisplatin in rats. Balkan Med J. 2013; 30(2): 235-241.[CrossRef]
  • Köroğlu KM, Çevik Ö, Şener G, Ercan F. Apocynin alleviates cisplatin-induced testicular cytotoxicity by regulating oxidative stress and apoptosis in rats. Andrologia. 2019; 8: 13227. [CrossRef]
  • Ju SM, Pae HO, Kim WS, Kang DG, Lee HS, Jeon BH. Role of reactive oxygen species in p53 activation during cisplatin-induced apoptosis of ratmesangial cells. Eur Rev Med Pharmacol Sci. 2014; 18(8): 1135-1141.
  • Boroja T, Katanic J, Rosić G, Selakovic D, Joksimovic J, Misic D, Stankovic V, Jovicic N, Mihailovic V. Summer savory (Satureja hortensis L.) extract: Phytochemical profile and modulatin of cisplatin-induced liver, renal and testicular toxicity. Food Chem Toxicol. 2018; 118: 252-263. [CrossRef]
  • Kilarkaje N, Mousa AM, Al-Bader MM, Khan KM. Antioxidants enhance the recovery of three cycles of bleomycin, etoposide, and cisplatin-induced testicular dysfunction, pituitary-testicular axis, and fertility in rats. Fertil Steril. 2013; 100(4): 1151-1159. [CrossRef]
  • Işeri S, Ercan F, Gedik N, Yüksel M, Alican I. Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicology.2007; 230(2-3): 256-264. [CrossRef]
  • 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; 2012: 362049. [CrossRef]
  • Abarikwu SO, Olufemi PD, Lawrence CJ, Wekere FC, Ochulor AC, Barikuma AM. Rutin, an antioxidant flavonoid, induces glutathione and glutathione peroxidase activities to protect against ethanol effects in cadmium-induced oxidative stress in the testis of adult rats. Andrologia. 2017; 49(7). [CrossRef]
  • Tekin G, İsbir S, Şener G, Çevik Ö, Çetinel Ş, Dericioğlu O, Arsan S, Çobanoğlu A. The preventive and curative effects of melatonin against abdominal aortic aneurysm in rats. J Vasc Surg. 2018; 67(5): 1546-1555. [CrossRef]
  • Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014; 740: 364-378.[CrossRef]
  • Fouad AA, Qutub HO, Fouad AEA, Audeh AM, Al-Melhim WN. Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes. Pharm Biol. 2017; 55(1): 1710-1714. [CrossRef]
  • Gevrek F, Erdemir F. Investigation of the effects of curcumin, vitamin E and their combination in cisplatin-induced testicular apoptosis using immunohistochemical technique. Turk J Urol. 2018; 44(1): 16-23. [CrossRef]
  • Yaman O, Topcu-Tarladacalisir Y. L-carnitine counteracts prepubertal exposure to cisplatin induced impaired sperm in adult rats by preventing germ cell apoptosis. Biotech Histochem. 2018; 93(3): 157-167. [CrossRef]
  • Aksu EH, Kandemir FM, Özkaraca M, Ömür AD, Küçükler S, Çomaklı S. Rutin ameliorates cisplatin-induced reproductive damage via suppression of oxidative stress and apoptosis in adult male rats. Andrologia. 2017; 49(1). [CrossRef]
  • Anand H, Misro MM, Sharma SB, Prakash S. Protective effects of Eugenia jambolana extract versus N-acetyl cysteine against cisplatin-induced damage in rat testis. Andrologia. 2015; 47(2): 194-208. [CrossRef]
  • Hao Q, Xiao X, Zhen J, Feng J, Song C, Jiang B, Hu Z. Resveratrol attenuates acute kidney injury by inhibiting death receptor mediated apoptotic pathways in a cisplatin induced rat model. Mol Med Rep. 2016; 14(4): 3683-3689. [CrossRef]
  • Wang J, He D, Zhang Q, Han Y, Jin S, Qi F. Resveratrol protects against Cisplatin-induced cardiotoxicity by alleviating oxidative damage. Cancer Biother Radiopharm. 2009; 24(6): 675-680. [CrossRef]
  • Alturfan AA, Tozan-Beceren A, Sehirli AO, Demiralp E, Sener G, Omurtag GZ. Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats. Mol Biol Rep. 2012; 39(4): 4589-4596. [CrossRef]
  • Yuluğ E, Türedi S, Karagüzel E, Kutlu O, Menteşe A, Alver A. The short term effects of resveratrol on ischemiareperfusion injury in rat testis. J Pediatr Surg. 2014; 49(3): 484-489. [CrossRef]
  • Eleawa SM, Alkhateeb MA, Alhashem FH, Bin-Jaliah I, Sakr HF, Elrefaey HM, Elkarib AO, Alessa RM, Haidara MA, Shatoor AS, Khalil MA. Resveratrol reverses cadmium chloride-induced testicular damage and subfertility by downregulating p53 and Bax and upregulating gonadotropins and Bcl-2 gene expression. J Reprod Dev. 2014; 60(2): 115-127. [CrossRef]
  • Archana D, Supriya C, Girish BP, Kishori B, Reddy PS. Alleviative effect of resveratrol on polyvinyl chloride-induced reproductive toxicity in male Wistar rats. Food Chem Toxicol. 2018; 116 (Pt B): 173-181. [CrossRef]
  • Singh I, Goyal Y, Ranawat P. Potential chemoprotective role of resveratrol against cisplatin induced testicular damage in mice. Chem Biol Interact. 2017; 273: 200-211. [CrossRef]
  • Reddy KP, Madhu P, Reddy PS. Protective effects of resveratrol against cisplatin-induced testicular and epididymal toxicity in rats. Food Chem Toxicol. 2016; 91: 65-72. [CrossRef]
  • Erkanlı Şentürk G, Ersoy Canillioĝlu Y, Umay C, Demiralp-Eksioglu E, Ercan F. Distribution of Zonula Occludens-1 and Occludin and alterations of testicular morphology after in utero radiation and postnatal hyperthermia in rats. Int J Exp Pathol. 2012; 93(6): 438-449. [CrossRef]
  • Beuge JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52: 302-310. [CrossRef]
  • Beutler, E. (1975). Glutathione in red blood cell metabolism. In: Beutler E (ed.). A Manuel of Biochemical Methods. 91; 112-144.
  • Hillegas LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assesment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods.1990; 24: 285-295. [CrossRef]
Journal of research in pharmacy (online)-Cover
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: Marmara Üniversitesi
Sayıdaki Diğer Makaleler

Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam

Meltem ÇETİN, Afife, Büşra KANDİLLİ, Fatma DEMİRKAYA

Preparation, optimization and in vivo anti-inflammatory Preparation, optimization and in vivo anti-inflammatory evaluation of hydroquinone loaded microemulsion formulations for melasma treatment

Mehmet Evren OKUR, Neslihan ÜSTÜNDAĞ OKUR, Şule AYLA, Emre Şefik ÇAĞLAR, Ahmet Nezihi PEKCAN

Optimization of the conditions of the extraction and purification stages of the Shilajit substance

Fedor BUGAEV, Dmitriy KOMPANTSEV, Lyudmila POGRENYAK

Resveratrol treatment reduces apoptosis and morphological alterations in cisplatin induced testis damage

Nagehan ÖZYILMAZ YAY, Feriha ERCAN, Göksel ŞENER

Anti-inflammatory effects of Lycium barbarum leaf extracts in lipopolysaccharide-induced RAW 264.7 macrophage cells and isolation of secondary metabolites

Hande SİPAHİ, Hasan KIRMIZIBEKMEZ, Ozan ŞEN, Beril KADIOĞLU YAMAN, Aycan SALMA, Norbert KUSZ, Judit HOHMANN

Morphology, myxocarpy, mineral content and in vitro antimicrobial and antiproliferative activities of mericarps of the vulnerable Turkish endemic Salvia pilifera

Mahmut ÜLGER, İbrahim BOZGEYİK, Özkan SARIKAYA, Sevda GÜZEL, Yusuf ÖZAY, Ahmet KAHRAMAN

Evaluation of the concurrent use of lidocaine and ketamine infusions as adjunctive analgesia in the intensive care unit

Alex EBIED, Abigail ANTIGUA

Purification of acethylcholinesterase from the mollusc Mytilus galloprovincialis Lam. and investigation of its kinetic properties

Nurten ÖZSOY, Gözde HASBAL, Sezin ANIL, Servet DURANAY

Inhibitory activity of Lactobacillus plantarum ATCC 8014 fermented milk combined with aqueous extract of Moringa oleifera leaves against Streptococcus mutans

Idha KUSUMAWATİ, Isnaeni ISNAENİ, Agustin MAULİDİNA, Erni Maduratna

Synthesis, characterization and investigation of cholinesterase enzyme inhibition and antioxidant activities of some 4-aryl-1,4-dihydropyridine derivatives

Hasan Erdinç SELLİTEPE, Gamze EROĞLU, İnci Selin DOĞAN, Burak BARUT, Arzu ÖZEL