Journal of Animal Reproduction and Biotechnology (한국동물생명공학회지)

The Korean Society of Animal Reproduction and Biotechnology (한국동물생명공학회)
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Catechin hydrate prevents cisplatin-induced spermatogonia GC-1 spg cellular damage

  • Hyeon Woo Shim (Department of Animal Biotechnology, College of Life Science, Sangji University) ;
  • Won-Yong Lee (Department of Livestock, Korea National University of Agriculture and Fisheries) ;
  • Youn-Kyung Ham (Department of Animal Science, College of Life Science, Sangji University) ;
  • Sung Don Lim (Department of Plant Life and Resource Science, College of Life Science, Sangji University) ;
  • Sun-Goo Hwang (Department of Plant Life and Resource Science, College of Life Science, Sangji University) ;
  • Hyun-Jung Park (Department of Animal Biotechnology, College of Life Science, Sangji University)
  • Received : 2024.06.04
  • Accepted : 2024.06.13
  • Published : 2024.06.30
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Abstract

Background: Despite its anticancer activity, cisplatin exhibits severe testicular toxicity when used in chemotherapy. Owing to its wide application in cancer therapy, the reduction of damage to normal tissue is of imminent clinical need. In this study, we evaluated the effects of catechin hydrate, a natural flavon-3-ol phytochemical, on cisplatin-induced testicular injury. Methods: Type 2 mouse spermatogonia (GC-1 spg cells) were treated with 0-100 μM catechin and cisplatin. Cell survival was estimated using a cell proliferation assay and Ki-67 immunostaining. Apoptosis was assessed via flow cytometry with the Dead Cell Apoptosis assay. To determine the antioxidant effects of catechin hydrate, Nrf2 expression was measured using qPCR and CellROX staining. The anti-inflammatory effects were evaluated by analyzing the gene and protein expression levels of iNOS and COX2 using qPCR and immunoblotting. Results: The 100 μM catechin hydrate treatment did not affect healthy GC-1 spg cells but, prevented cisplatin-induced GC-1 spg cell death via the regulation of anti-oxidants and inflammation-related molecules. In addition, the number of apoptotic cells, cleaved-caspase 3 level, and BAX gene expression levels were significantly reduced by catechin hydrate treatment in a cisplatin-induced GC-1 spg cell death model. In addition, antioxidant and anti-inflammatory marker genes, including Nrf2, iNOS, and COX2 were significantly downregulated by catechin hydrate treatment in cisplatintreated GC-1 cells. Conclusions: Our study contributes to the opportunity to reintroduce cisplatin into systemic anticancer treatment, with reduced testicular toxicity and restored fertility.

Keywords

Acknowledgement

This study was supported by the Sangji University Research Fund 2023.

References

  1. Alshatwi AA, Hasan TN, Alqahtani AM, Syed NA, Shafi G, AlAssaf AH, Al-Khalifa AS. 2014. Delineating the anti-cytotoxic and anti-genotoxic potentials of catechin hydrate against cadmium toxicity in human peripheral blood lymphocytes. Environ. Toxicol. Pharmacol. 38:653-662. 
  2. Aly HAA and Eid BG. 2020. Cisplatin induced testicular damage through mitochondria mediated apoptosis, inflammation and oxidative stress in rats: impact of resveratrol. Endocr. J. 67:969-980. 
  3. Bae KH, Tan S, Yamashita A, Ang WX, Gao SJ, Wang S, Chung JE, Kurisawa M. 2017. Hyaluronic acid-green tea catechin micellar nanocomplexes: fail-safe cisplatin nanomedicine for the treatment of ovarian cancer without off-target toxicity. Biomaterials 148:41-53. 
  4. Bernatoniene J and Kopustinskiene DM. 2018. The role of catechins in cellular responses to oxidative stress. Molecules 23:965. 
  5. Bhardwaj P and Khanna D. 2013. Green tea catechins: defensive role in cardiovascular disorders. Chin. J. Nat. Med. 11: 345-353. 
  6. Chacko SM, Thambi PT, Kuttan R, Nishigaki I. 2010. Beneficial effects of green tea: a literature review. Chin. Med. 5:13. 
  7. Cherry SM, Hunt PA, Hassold TJ. 2004. Cisplatin disrupts mammalian spermatogenesis, but does not affect recombination or chromosome segregation. Mutat. Res. 564:115-128. 
  8. Dasari S and Tchounwou PB. 2014. Cisplatin in cancer therapy: molecular mechanisms of action. Eur. J. Pharmacol. 740: 364-378. 
  9. Fan FY, Sang LX, Jiang M. 2017. Catechins and their therapeutic benefits to inflammatory bowel disease. Molecules 22:484. 
  10. Fouad AA, Qutub HO, Fouad AEA, Audeh AM, Al-Melhim WN. 2017. Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes. Pharm. Biol. 55:1710-1714. 
  11. Fujiki H, Sueoka E, Watanabe T, Suganuma M. 2015. Synergistic enhancement of anticancer effects on numerous human cancer cell lines treated with the combination of EGCG, other green tea catechins, and anticancer compounds. J. Cancer Res. Clin. Oncol. 141:1511-1522. 
  12. Garcia MM, Acquier A, Suarez G, Gomez NV, Gorostizaga A, Mendez CF, Paz C. 2012. Cisplatin inhibits testosterone synthesis by a mechanism that includes the action of reactive oxygen species (ROS) at the level of P450scc. Chem. Biol. Interact. 199:185-191. 
  13. Graham HN. 1992. Green tea composition, consumption, and polyphenol chemistry. Prev. Med. 21:334-350. 
  14. Ismail HY, Shaker NA, Hussein S, Tohamy A, Fathi M, Rizk H, Wally YR. 2023. Cisplatin-induced azoospermia and testicular damage ameliorated by adipose-derived mesenchymal stem cells. Biol. Res. 56:2. 
  15. Izzo C, Vitillo P, Di Pietro P, Visco V, Strianese A, Virtuoso N, Ciccarelli M, Galasso G, Carrizzo A, Vecchione C. 2021. The role of oxidative stress in cardiovascular aging and cardiovascular diseases. Life (Basel) 11:60. 
  16. Lee WY and Park HJ. 2023. T-2 mycotoxin induces male germ cell apoptosis by ROS-mediated JNK/p38 MAPK pathway. Ecotoxicol. Environ. Saf. 262:115323. 
  17. Li XX, Liu C, Dong SL, Ou CS, Lu JL, Ye JH, Liang YR, Zheng XQ. 2022. Anticarcinogenic potentials of tea catechins. Front. Nutr. 9:1060783. 
  18. Maines MD, Sluss PM, Iscan M. 1990. Cis-platinum-mediated decrease in serum testosterone is associated with depression of luteinizing hormone receptors and cytochrome P450scc in rat testis. Endocrinology 126:2398-2406. 
  19. Razavi S, Khadivi F, Hashemi F, Bakhtiari A. 2019. Effect of zinc on spermatogenesis and sperm chromatin condensation in bleomycin, etoposide, cisplatin treated rats. Cell J. 20:521-526. 
  20. Reddy KP, Madhu P, Reddy PS. 2016. Protective effects of resveratrol against cisplatin-induced testicular and epididymal toxicity in rats. Food Chem. Toxicol. 91:65-72. 
  21. Romani AMP. 2022. Cisplatin in cancer treatment. Biochem. Pharmacol. 206:115323. 
  22. Sadler DG, Barlow J, Draijer R, Jones H, Thijssen DHJ, Stewart CE. 2022. (-)-Epicatechin alters reactive oxygen and nitrogen species production independent of mitochondrial respiration in human vascular endothelial cells. Oxid. Med. Cell Longev. 2022:4413191. 
  23. Scalbert A, Manach C, Morand C, Remesy C, Jimenez L. 2005. Dietary polyphenols and the prevention of diseases. Crit. Rev. Food Sci. Nutr. 45:287-306. 
  24. Sharma P and Goyal PK. 2015. Ameliorative effect of green tea catechin against cadmium chloride-induced testicular toxicity in mice. J. Environ. Pathol. Toxicol. Oncol. 34:335-352. 
  25. Sheng Y, Sun Y, Tang Y, Yu Y, Wang J, Zheng F, Li Y, Sun Y. 2023. Catechins: protective mechanism of antioxidant stress in atherosclerosis. Front. Pharmacol. 14:1144878. 
  26. Sherif IO, Abdel-Aziz A, Sarhan OM. 2014. Cisplatin-induced testicular toxicity in rats: the protective effect of arjunolic acid. J. Biochem. Mol. Toxicol. 28:515-521. 
  27. Wang TE, Lai YH, Yang KC, Lin SJ, Chen CL, Tsai PS. 2020. Counteracting cisplatin-induced testicular damages by natural polyphenol constituent honokiol. Antioxidants (Basel) 9:723. 
  28. Yu PL, Pu HF, Chen SY, Wang SW, Wang PS. 2010. Effects of catechin, epicatechin and epigallocatechin gallate on testosterone production in rat Leydig cells. J. Cell Biochem. 110:333-342. 
  29. Zhong Z, Dong Z, Yang L, Chen X, Gong Z. 2012. Inhibition of proliferation of human lung cancer cells by green tea catechins is mediated by upregulation of let-7. Exp. Ther. Med. 4:267-272.