Yıl: 2022 Cilt: 5 Sayı: 1 Sayfa Aralığı: 10 - 22 Metin Dili: İngilizce DOI: 10.30714/j-ebr.2022173847

Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage

Öz:
Aim: In this study, utilizing the in vivo Copenhagen rat model possessing prostate cancer, we studied the possible impact of tumorigenesis on testes and liver morphology and whether riluzole (RIL) and ranolazine (RNL) treatment would have any affect or not. Method: Male Copenhagen rats were divided into four groups: 1) Control group, 2) Cancer group, 3) Cancer + 10 μM Riluzole 4), and Cancer + 2.5 μM / 5 μM Ranolazine group. The tissue samples of testes and liver were taken and processed for light microscopy, including staining with hematoxylin and eosin. Results: In the cancer group, degenerated seminiferous tubules, cell remnants in the lumen were shown in the testis, and a decrease in the spermatogenic cell line was found. The deterioration in these parameters was milder in the treatment groups and an increase in the number of normal tubules was found. In the cancer group, pyknotic nucleus, mononuclear cell infiltration, hyperemia, vacuolization, disrupted arrangement of hepatocyte plates, sinusoidal dilatations, and degenerated hepatocytes were observed in the liver. However, there was a slight damage in cancer + 10 μM RIL, cancer + 2.5 μM RNL, and cancer + 5 μM RNL groups. Properly hepatocyte arrangement and sinusoidal enlargement were observed. Conclusions: This treatment can be considered a promising protective adjuvant candidate for testes and liver tissue in prostate cancer or cancer therapy-related damage.
Anahtar Kelime:

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  • [1] Dolfi SC, Medina DJ, Kareddula A, et al. Riluzole exerts distinct antitumor effects from a metabotropic glutamate receptor 1- specific inhibitor on breast cancer cells. Oncotarget. 2017; 8(27):44639-53.
  • [2] Rizaner N, Uzun S, Fraser SP, et al. Riluzole: Anti-invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions. Basic Clin Pharmacol. 2020;127(4):254-64.
  • [3] Raghubir M, Nowshin Rahman C, Fang J, et al. Osteosarcoma growth suppression by riluzole delivery via iron oxide nanocage in nude mice. Oncol Rep. 2020;43(1): 169–76.
  • [4] Hale SL, Shryock JC, Belardinelli L, et al. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol. 2008;44(6):954-67.
  • [5] Antzelevitch C, Nesterenko V, Shryock JC, et al. The role of late I Na in development of cardiac arrhythmias. Handb Exp Pharmacol. 2014; 221:137-68.
  • [6] Nelson M, Yang M, Millican-Slater R, et al. Nav1.5 regulates breast tumor growth and metastatic dissemination in vivo. Oncotarget. 2015;6 (32):32914–29.
  • [7] Bugan I, Kucuk S, Karagoz Z, et al. Antimetastatic effect of ranolazine in an in vivo rat model of prostate cancer, and expression of voltage-gated sodium channel protein in human prostate. Prostate Cancer Prostatic Dis. 2019; 22 (4):569-79.
  • [8] Ajroud-Driss S, Saeed M, Khan H, et al. Riluzole metabolism and CYP1A1/2 polymorphisms in patients with ALS. Amyotroph Lateral Scler. 2007; 8(5):305- 309.
  • [9] Cheng JW. Ranolazine for the management of coronary artery disease. Clinical Therapeutics. 2006; 28(12):1996-2007.
  • [10] Thu YM, Richmond A. NF-κB inducing kinase: a key regulator in the immune system and in cancer. Cytokine Growth Factor Rev. 2010;21(4):213-26.
  • [11] Valiño-Rivas L, Vaquero JJ, Sucunza D, et al. NIK as a Druggable Mediator of Tissue Injury. Trends Mol Med. 2019; 25 (4):341- 60.
  • [12] Farhood B, Khodamoradi E, Hoseini- Ghahfarokhi M, et al. TGF-β in radiotherapy: mechanisms of tumor resistance and normal tissues injury. Pharmacol Res. 2020; 155:104745.
  • [13] Guth A, Monk E, Agarwal R, et al. Targeting Fat Oxidation in Mouse Prostate Cancer Decreases Tumor Growth and Stimulates Anti-Cancer Immunity. Int J Mol Sci. 2020; 21(24): 9660.
  • [14] Pienta KJ, Abate-Shen C, Agus DB, et al. The current state of preclinical prostate cancer animal models. Prostate. 2008;68 (6):629-39.
  • [15] Tennant TR, Kim H, Sokoloff M, et al. The Dunning model, Prostate. 2000; 43 (4):295- 302.
  • [16] Bugan I, Karagoz Z, Altun S, et al. Gabapentin, an analgesic used against cancer-associated neuropathic pain: Effects on prostate cancer progression in an in vivo rat model. Basic Clin Pharmacol Toxicol. 2016; 118(3): 200–207.
  • [17] Wang T, Huang W, Cheng F. Baclofen a GABAB receptor ago- 679 nist, inhibits human hepatocellular carcinoma cell growth in vitro 680 and in vivo. Life Sci. 2008; 82 (9-10):536–41.
  • [18] Hess RA, Linder RE, Strader LF, et al. Acute effects and long term sequelae of 1,3- dinitrobenzene on male reproduction in the rat II. quantitative and qualitative histopathology of the testis. J Androl. 1988; 9(5): 327- 42.
  • [19] Bhattacharya A, Dhar P, Mehra RD. Preliminary morphological and biochemical changes in rat liver following postnatal exposure to sodium arsenite. Anat Cell Biol. 2012; 45 (4): 229-40.
  • [20] Siegel RL, Miller KD, Jemal A. Cancer statistics, CA: Cancer J. Clin. 2019; 69(1):7- 34.
  • [21] Sperling S, Aung T, Martin S, et al. Riluzole: a potential therapeutic intervention in human brain tumor stem-like cells. Oncotarget. 2017; 20(57):96697-96709.
  • [22] Taguchi YH, Wang H. Genetic Association between Amyotrophic Lateral Sclerosis and Cancer. Genes (Basel). 2017; 8(10):243.
  • [23] Speyer C, Nassar MA, Hachem AH, et al. Riluzole mediates anti-tumor properties in breast cancer cells independent of metabotropic glutamate receptor 1. Breast Cancer Res Treat. 2016; 157:217-28.
  • [24] Lemieszek MK, Stepulak A, Sawa-Wejksza K, et al. Riluzole Inhibits Proliferation, Migration and Cell Cycle Progression and Induces Apoptosis in Tumor Cells of Various Origins. Anti-Cancer Agents Med Chem. 2018;18 (4):565-72.
  • [25] Wadosky KM, Shourideh M, Goodrich DW, et al. Riluzole induces AR degradation via endoplasmic reticulum stress pathway in androgen-dependent and castration-resistant prostate cancer cells. Prostate. 2019;79 (2):140-150.
  • [26] Rayner‐Hartley E, Sedlak T. Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016;5(3):e003196.
  • [27] Riccio G, Antonucci S, Coppola C, et al. Ranolazine Attenuates Trastuzumab- Induced Heart Dysfunction by Modulating ROS Production. Front physiol. 2018; 9:38.
  • [28] Al Batran R, Gopal K, Aburasayn H, et al. The antianginal ranolazine mitigates obesity-induced nonalcoholic fatty liver disease and increases hepatic pyruvate dehydrogenase activity. JCI Insight. 2019; 4 (1): e124643.
  • [29] Teschke R. Hepatotoxicity: Molecular Mechanisms and Pathophysiology. Int J Mol Sci. 2019; 20 (1): 211.
  • [30] Smith R, Kaune H, Parodi D, et al. Increased sperm DNA damage in patients with varicocele relationship with seminal oxidative stress. Hum Reprod. 2006; 21(4): 986–993.
  • [31] Hoppe BS, Harris S, Rhoton-Vlasak A, et al. Sperm preservation and neutron contamination following proton therapy for prostate cancer study. Acta Oncol. 2017;56(1):17-20.
  • [32] [32] Campara Z, Simic D, Aleksic P, et al. Metastasis of prostate adenocarcinoma to the testis. Med Arch. 2016; 70(4): 318-20.
  • [33] Raghuvanshi K, Deshmukh H, Raval A, et al. Cancer prostate metastasis to testis: A rare encounter, 2018; 1(2): 94-96.
  • [34] Vdoviaková K, Vdoviaková K, Petrovová E, et al. Importance rat liver morphology and vasculature in surgical research. Med Sci Monit. 2016; 22: 4716-28.
  • [35] Ma B, Wells A, Wei L, et al. Prostate cancer liver metastasis: Dormancy and resistance to therapy, Seminars in Cancer Biology. 2021; 71: 2-9.
  • [36] Biber A, Durusu IZ, Özen C. In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. Turk J Biol. 2018; 42 (5):414-21.
  • [37] Turanli B, Grøtli M, Boren J, et al. Drug Repositioning for Effective Prostate Cancer Treatment. Front physiol. 2018; 9:500.
  • [38] Xue H, Li J, Xie H, et al. Review of Drug Repositioning Approaches and Resources. Int J Biol Sci. 2018;14 (10):1232-44.
  • [39] Ozdemir A, Ark M. A novel ROCK inhibitor: off-target effects of metformin. Turk J Biol. 2021; 45 (1):35-45.
APA KÖROĞLU P, BUGAN İ (2022). Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. , 10 - 22. 10.30714/j-ebr.2022173847
Chicago KÖROĞLU Pınar,BUGAN İlknur Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. (2022): 10 - 22. 10.30714/j-ebr.2022173847
MLA KÖROĞLU Pınar,BUGAN İlknur Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. , 2022, ss.10 - 22. 10.30714/j-ebr.2022173847
AMA KÖROĞLU P,BUGAN İ Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. . 2022; 10 - 22. 10.30714/j-ebr.2022173847
Vancouver KÖROĞLU P,BUGAN İ Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. . 2022; 10 - 22. 10.30714/j-ebr.2022173847
IEEE KÖROĞLU P,BUGAN İ "Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage." , ss.10 - 22, 2022. 10.30714/j-ebr.2022173847
ISNAD KÖROĞLU, Pınar - BUGAN, İlknur. "Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage". (2022), 10-22. https://doi.org/10.30714/j-ebr.2022173847
APA KÖROĞLU P, BUGAN İ (2022). Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. Experimental Biomedical Research, 5(1), 10 - 22. 10.30714/j-ebr.2022173847
Chicago KÖROĞLU Pınar,BUGAN İlknur Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. Experimental Biomedical Research 5, no.1 (2022): 10 - 22. 10.30714/j-ebr.2022173847
MLA KÖROĞLU Pınar,BUGAN İlknur Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. Experimental Biomedical Research, vol.5, no.1, 2022, ss.10 - 22. 10.30714/j-ebr.2022173847
AMA KÖROĞLU P,BUGAN İ Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. Experimental Biomedical Research. 2022; 5(1): 10 - 22. 10.30714/j-ebr.2022173847
Vancouver KÖROĞLU P,BUGAN İ Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage. Experimental Biomedical Research. 2022; 5(1): 10 - 22. 10.30714/j-ebr.2022173847
IEEE KÖROĞLU P,BUGAN İ "Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage." Experimental Biomedical Research, 5, ss.10 - 22, 2022. 10.30714/j-ebr.2022173847
ISNAD KÖROĞLU, Pınar - BUGAN, İlknur. "Riluzole and ranolazine application of prostate cancer: Cancer related testicular and liver tissue damage". Experimental Biomedical Research 5/1 (2022), 10-22. https://doi.org/10.30714/j-ebr.2022173847