D-Ribose-L-Cysteine-rich Supplement Attenuate Doxorubicin-Induced Impaired Spermatogenesis, Testicular Steroidogenesis and Redox Status in Sprague-Dawley Rats
Keywords:Cellgevity™, doxorubicin, antioxidant, testosterone, sperm parameters
Reproductive function is often impaired during chemotherapy and currently there is no universally approved drug/supplement that can effectively protect the testis from cellular assault due to chemotherapeutic agent such as doxorubicin (dox). This study was designed to investigate the efficacy of D-Ribose-L-Cysteine rich supplement, Cellgevity™ (cgvt), in ameliorating some doxorubicin-induced testicular damage in Sprague-Dawley rats. At the end of the study, biochemical assays and sperm epididymal parameters analysis were done. Our results show that simultaneous administration of cgvt and doxorubicin has ameliorative effect on the testis when compared to pre-treatment or post-treatment with cgvt. Significant increase in testosterone, sperm concentration, progressive motility and significant decrease in immotility were observed in the cellgevity treated group. Also, simultaneous administration of cgvt with dox reduced lipid peroxidation and boosted only glutathione level in testicular tissues. Nevertheless, pre-treatment or post-treatment with cgvt did not play a significant role in modulating sperm parameters, hormones and tissue oxidative stress level. This result reveals that cellgevity has testiculo-protective effect against doxorubicin administration.
Attesahin AI, Karahan G, Turk S, Gur SY, Ceribasi AO (2006). Protective role of lycopene on cisplatin-induced changes in sperm characteristics, testicular damage and oxidative stress in rats. Reprod Toxicol. 21:42-47.
Badkoobeh P, Parivar K, Kalantar SM, Hosseini SD, and Salabat A (2013). Effect of nano-zinc oxide on doxorubicin- induced oxidative stress and sperm disorders in adult male Wistar rats. Iran J Reprod Med. 11(5): 355–364.
Bieber AM, Marcon L, Hales BF, Robaire B (2006). Effects of chemotherapeutic agents of testicular cancer on the male rat reproductive system, spermatozoa and fertility. J ANDROL. 27:189-200.
Box VG (2007). The intercalation of DNA double helices with doxorubicin and nogalamycin. J Mol Graph Model. 26(1):14-9.
Carlsen E, Giwercman A, Keiding N, Skakkebaek NE (1992). Evidence for decreasing quality of semen during past 50 years. BMJ. 305: 609–613.
Carvalho C, Santos XR, Cardoso S, Correia S, Oliveira JP, Santos MS, Moreiera LP (2009). Doxorubicin: The good, the bad and the ugly effect. Curr med chem. 16: 3267-3285.
Chuan H, Baishun L, Kongrong X, Dan L, Jing H, Yang Y, HongChuan N, Liqing F, Wenbing Z (2017). Decline in semen quality among 30,636 young Chinese men from 2001 to 2015. Fertil. Steril. 107 (1): 83-88.
Chularojmontri L, Wattanapitayakul SK, Herunsalee A, Charuchongkolwongse S, Niumsakul N, Srichairat S (2005). Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on doxorubicin-induced cardiotoxicity. Biol. Pharm. Bull. 28:1165-1171.
Cutts S, Swift L, Rephaaeli A, Nudelman A, Philips D (2005). Recent advances in understanding and exploiting the activation of anthracyclines by formaldehyde. Curr Med Chem Anticancer Agents. 5:431-447.
Danesi R, Fogli S, Gennari A, Conte P, Del Tacca M (2002). Pharmacokinetic pharmacodynamics relationship of the anthracycline anticancer drugs. Clin Pharmacokinet. 41: 431-444.
Ellman GL (1959). Tissue sulfhydryl groups. Arch Biochem Biophys. 82(1): 70-77.
Falana B, Adeleke O, Orenolu M, Osinubi A, Oyewopo A (2017). Effect of D-ribose-L-cysteine on aluminum induced testicular damage in male Sprague-Dawley rats. JBRA Assist Reprod. 21(2): 94-100.
Gruber B, Anuszewska E, Priebe W (2004). The effect of new anthracycline derivatives on the induction of apoptotic processes in human neoplastic cells. Folia Histochem Cytobiol. 42: 127-130.
Irvine DS (2000). Male reproductive health: cause for concern? Andrologia 32(4): 195-208.
Ishikawa T, Kamidono S, Fujisawa M (2004). Fertility after high dose chemotherapy for testicular cancer. Urology. 63: 137-140.
Kern JC, Kehrer JP (2005). Free radicals and apoptosis: relationships with glutathione, thioredoxin, and the BCL family of proteins. Front Biosci. 10:1727-1738.
Latchoumycandane C, Chitra KC, Mathur PP (2002). The effect of methoxychlor on the epididymal antioxidant system of adult rats. Reprod Toxicol. 16(2):161-72.
Max International (2017). Retrieved from https://www.max.com/cellgevity/undefined/us/en
Mihara M, Uchiyama M (1978). Determination of malondialdehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 86(1):271-278.
O’Shaughnessy, J (2003). Liposomal anthracycline for breast cancer: overview. Oncology. 8:1-2.
Patil RL, Balaraman R (2009). Effect of melatonin on doxorubicin testicular damage in rats. Int J PharmTech Res. 1:879-84.
Pectasides D, Pectasides M, Farmakis D, Nikolaou M, Koumpou M, Kostopoulou V, Mylonakis N (2004). Testicular function in patients with testicular cancer treated with bloeomycin-etoposide-carboplatin (BEC(90)) combination chemotherapy. Eur Urol. 45:187-193.
Petrioli R, Fiaschi A, Francini E, Pascucci A, Francini G (2008). The role of doxorubicin and epirubicin in the treatment of patients with metastatic hormone refractory prostate cancer. Cancer Treat Rev. 34:710-718.
Prahalatan C, Selvekuma E, Varalakshmi P (2005). Lipoic acid ameliorates adriamycin-induced testicular mitochondriopathy. Reprod Toxicol. 20:111-116.
Priestman T (2008). Cancer Chemotherapy in Clinical Practice. Springer-Verlag, London, UK., SBN:978-1-84628-989-7, pp:130-136.
Saalu LC, Osinubi AAA, Jewo PI, Oyewopo AO, Ajayi GO (2010). An evaluation of influence of Citrus paradisi seed extract on doxorubicin induced testicular oxidative stress and impaired spermatogenesis. ANSInet. 1(1): 41-52.
Schafer FQ, Buettner GR (2001). Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 30(11):1191-212.
Schulster M, Bernie AM, Ramasamy R (2016). The role of estradiol in male reproductive function. Asian J Androl. 18(3): 435–440.
Sivaraj A, Vinothkumar P, Sathiyaraj K, Sundaresan S, Devi K, Senthilkumar B (2011). Hepatoprotective potential of Andrographis paniculata aqueous leaf extract on ethanol induced liver toxicity in albino rats. J Appl Pharm Sci. 01 (06):204-208.
Sun M, Zigma S (1978). An Improved Spectrophotometer Assay of Superoxide Dismutase Based On Epinephrine Antioxidation. Anal. Biochem. 90: 81-89.
Suntres ZE (2011). Liposomal Antioxidants for Protection against Oxidant-Induced Damage. J Toxicol. 2011:152474. doi: 10.1155/2011/152474.
Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P (2008). Redox regulation of cell survival. Antioxid Redox Signal. 10(8):1343-1374.
Traila A, Dima D, Achimas-Cadariu P, Micu R (2018). Fertility preservation in Hodgkin’s lymphoma patients that undergo targeted molecular therapies: an important step forward from the chemotherapy era. Cancer Manag. Res. 10: 1517–1526.
Uyeturk U, Uyeturk U, Firat T, Cetinkaya A, Kin Tekce B, Cakir S (2014). Protective Effects of Rosmarinic Acid on Doxorubicin-Induced Testicular Damage. Chemotherapy. 60:7-12.
Yokoi K, Mayi ZK (2004). Organ apoptosis with cytotoxic drugs. Toxicology. 290:78-85.