Toxicological Research

  • 제39권1호
  • /
  • Pages.115-125
  • /
  • 2023
  • /
  • 1976-8257(pISSN)
  • /
  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지
DOI QR코드

DOI QR Code

Exposure to China dust exacerbates testicular toxicity induced by cyclophosphamide in mice

  • Woong-Il, Kim (College of Veterinary Medicine, Chonnam National University) ;
  • Je-Oh, Lim (College of Veterinary Medicine, Chonnam National University) ;
  • So-Won, Pak (College of Veterinary Medicine, Chonnam National University) ;
  • Se-Jin, Lee (College of Veterinary Medicine, Chonnam National University) ;
  • In-Sik, Shin (College of Veterinary Medicine, Chonnam National University) ;
  • Changjong, Moon (College of Veterinary Medicine, Chonnam National University) ;
  • Jeong-Doo, Heo (Bioenvironmental Science & Technology Division, Korea Institute of Toxicology) ;
  • Jong-Choon, Kim (College of Veterinary Medicine, Chonnam National University)
  • 투고 : 2022.04.14
  • 심사 : 2022.08.03
  • 발행 : 2023.01.15
⟨ 이전 논문 다음 논문 ⟩

초록

This study investigated the potential effects of China dust (CD) exposure on cyclophosphamide (CP)-induced testicular toxicity in mice, focusing on spermatogenesis and oxidative damage. CP treatment reduced testicular and epididymal weight and sperm motility and enhanced sperm abnormality. Histopathological examination presented various morphological alterations in the testis, including increased exfoliation of spermatogenic cells, degeneration of early spermatogenic cells, vacuolation of Sertoli cells, a decreased number of spermatogonia/spermatocytes/spermatids, along with a high number of apoptotic cells. In addition, the testis exhibited reduced glutathione (GSH) levels and glutathione reductase (GR) activity and enhanced malondialdehyde (MDA) concentration. Meanwhile, CD exposure exacerbated testicular histopathological alterations induced by CP. CD exposure also aggravated oxidative damage by increasing the lipid peroxidative product MDA and decreasing GSH levels and antioxidant enzyme activities in the testis. These results suggest that CD exposure exacerbates CP-induced testicular toxicity in mice, which might be attributed to the induction of lipid peroxidation and reduced antioxidant activity.

키워드

과제정보

The authors would like to thank the researchers at Korea Institute of Toxicology for their technical support.

참고문헌

  1. Ahlmann M, Hempel G (2016) The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy. Cancer Chemother Pharmacol 78:661-671. https://doi.org/10.1007/s00280-016-3152-1
  2. Emadi A, Jones RJ, Brodsky RA (2009) Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol 6:638-647. https://doi.org/10.1038/nrclinonc.2009.146
  3. Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M (2017) The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol 13:525-536. https://doi.org/10.1080/17425255.2017.1277205
  4. Das UB, Mallick M, Debnath JM, Ghosh D (2002) Protective effect of ascorbic acid on cyclophosphamide-induced testicular gametogenic and androgenic disorders in male rats. Asian J Androl 4:201-207. https://pubmed.ncbi.nlm.nih.gov/12364977/
  5. Hoorweg-Nijman JJ, Delemarre-van de Waal HA, de Waal FC, Behrendt H (1992) Cyclophosphamide-induced disturbance of gonadotropin secretion manifesting testicular damage. Acta Endocrinol (Copenh) 126:143-148. https://doi.org/10.1530/acta.0.1260143
  6. Ghosh D, Das UB, Ghosh S, Mallick M (2002) Testicular gametogenic and steroidogenic activities in cyclophosphamide treated rat: a correlative study with testicular oxidative stress. Drug Chem Toxicol 25:281-292. https://doi.org/10.1081/dct-120005891
  7. Liu F, Li XL, Lin T, He DW, Wei GH et al (2012) The cyclophosphamide metabolite, acrolein, induces cytoskeletal changes and oxidative stress in Sertoli cells. Mol Biol Rep 39:493-500. https://doi.org/10.1007/s11033-011-0763-9
  8. Haenen GR, Vermeulen NP, Tai-Tin-Tsoi JN, Ragetli HM, Timmerman H et al (1988) Activation of the microsomal glutathione-S-transferase and reduction of the glutathione dependent protection against lipid peroxidation by acrolein. Biochem Pharmacol 37:1933-1938. https://doi.org/10.1016/0006-2952(88)90539-4
  9. Kim SH, Lee IC, Ko JW, Shin IS, Moon C et al (2016) Mechanism of protection by diallyl disulfide against cyclophosphamide-induced spermatotoxicity and oxidative stress in rats. Mol Cell Toxicol 12:301-312. https://doi.org/10.1007/s13273-016-0035-9
  10. Ertmer F, Oldenhof H, Schutze S, Rohn K, Wolkers WF et al (2017) Induced sub-lethal oxidative damage affects osmotic tolerance and cryosurvival of spermatozoa. Reprod Fertil 29:1739-1750. https://doi.org/10.1071/RD16183
  11. Kim K, Kim SD, Shin TH, Bae CS, Ahn T et al (2021) Respiratory and systemic toxicity of inhaled artificial Asian sand dust in pigs. Life (Basel) 11:25. https://doi.org/10.3390/life11010025
  12. Hashizume M, Kim Y, Ng CFS, Chung Y, Madaniyazi L et al (2020) Health effects of Asian dust: a systematic review and meta-analysis. Environ Health Perspect 128:66001. https://doi.org/10.1289/EHP5312
  13. Cheung K, Daher N, Kam W, Shafer MM, Ning Z et al (2011) Spatial and temporal variation of chemical composition and mass closure of ambient coarse particulate matter (PM10-2.5) in the Los Angeles area. Atmos Environ 45:2651-2662. https://doi.org/10.1016/j.atmosenv.2011.02.066
  14. Mori I, Nishikawa M, Tanimura T, Quan H (2003) Change in size distribution and chemical composition of kosa (Asian dust) aerosol during long-range transport. Atmos Environ 37:4253-4263. https://doi.org/10.1016/S1352-2310(03)00535-1
  15. Gualtieri M, Ovrevik J, Mollerup S, Asare N, Longhin E et al (2011) Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: effects on DNA, mitochondria, AhR binding and spindle organization. Mutat Res 713:18-31. https://doi.org/10.1016/j.mrfmmm.2011.05.011
  16. Ovrevik J (2019) Oxidative potential versus biological effects: a review on the relevance of cell-free/abiotic assays as predictors of toxicity from airborne particulate matter. Int J Mol Sci 20:4772. https://doi.org/10.3390/ijms20194772
  17. Li N, Xia T, Nel AE (2008) The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 44:1689-1699. https://doi.org/10.1016/j.freeradbiomed.2008.01.028
  18. Moller P, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M et al (2014) Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutat Res Rev Mutat Res 762:133-166. https://doi.org/10.1016/j.mrrev.2014.09.001
  19. NRC (National Research Council) (2011) Guide for the Care and Use of Laboratory Animals. National Research Council, National Academy, Washington, USA
  20. Lee KH, Lee DW, Kang BC (2020) The 'R' principles in laboratory animal experiments. Lab Anim Res 36:45. https://doi.org/10.1186/s42826-020-00078-6
  21. Abd-El-Tawab AM, Shahin NN, AbdelMohsen MM (2014) Protective effect of Satureja montana extract on cyclophosphamide-induced testicular injury in rats. Chem Biol Interact 224:196-205. https://doi.org/10.1016/j.cbi.2014.11.001
  22. Chabra A, Shokrzadeh M, Naghshvar F, Salehi F, Ahmadi A (2014) Melatonin ameliorates oxidative stress and reproductive toxicity induced by cyclophosphamide in male mice. Hum Exp Toxicol 33:185-195. https://doi.org/10.1177/0960327113489052
  23. Ko JW, Shin NR, Je-Oh L, Jung TY, Moon C et al (2020) Silica dioxide nanoparticles aggravate airway inflammation in an asthmatic mouse model via NLRP3 inflammasome activation. Regul Toxicol Pharmacol 112:104618. https://doi.org/10.1016/j.yrtph.2020.104618
  24. Park EJ, Kang MS, Jin SW, Lee TG, Lee GH et al (2021) Multiple pathways of alveolar macrophage death contribute to pulmonary inflammation induced by silica nanoparticles. Nanotoxicology 15:1087-1101. https://doi.org/10.1080/17435390.2021.1969461
  25. Lee KM, Lee IC, Kim SH, Moon C, Park SH et al (2012) Melatonin attenuates doxorubicin-induced testicular toxicity in rats. Andrologia 44:796-803. https://doi.org/10.1111/j.1439-0272.2011.01269.x
  26. Beladiya JV, Mehta AA (2021) Acute and 28-days subacute toxicity studies of Gαq-RGS2 signaling inhibitor. Lab Anim Res 37:17. https://doi.org/10.1186/s42826-021-00093-1
  27. Jeong YJ, Jeon H, Kim EJ, Ryu HY, Song KS et al (2022) Evaluation of the acute, sub-chronic and chronic oral toxicity, genetic toxicity, and safety of a Lomens-Po. Toxicol Res 38:69-90. https://doi.org/10.1007/s43188-021-00090-5
  28. Oakberg EF (1956) A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am J Anat 99:391-413. https://doi.org/10.1002/aja.1000990303
  29. Yang HW, Park JH, Shin JM, Lee HM, Park IH (2019) Asian sand dust upregulates IL-6 and IL-8 via ROS, JNK, ERK, and CREB signaling in human nasal fibroblasts. Am J Rhinol Allergy 34:249-261. https://doi.org/10.1177/1945892419890267
  30. Lim JO, Lee SJ, Kim WI, Pak SW, Kim JC et al (2021) Melatonin alleviates silica nanoparticle-induced lung inflammation via thioredoxin-interacting protein downregulation. Antioxidants 10:1765. https://doi.org/10.3390/antiox10111765
  31. Kim SH, Lee IC, Baek HS, Moon C, Kim SH et al (2013) Protective effect of diallyl disulfide on cyclophosphamide-induced testicular toxicity in rats. Lab Anim Res 29:204-211. https://doi.org/10.5625/lar.2013.29.4.204
  32. Tripathi DN, Jena GB (2008) Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology 248:96-103. https://doi.org/10.1016/j.tox.2008.03.015
  33. Ilbey YO, Ozbek E, Simsek A, Otunctemur A, Cekmen M et al (2009) Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats. Fertil Steril 92:1124-1132. https://doi.org/10.1016/j.fertnstert.2008.07.1758
  34. Yoshida S, Hiyoshi K, Ichinose T, Nishikawa M, Takano H et al (2009) Aggravating effect of natural sand dust on male reproductive function in mice. Reprod Med Biol 8:151-156. https://doi.org/10.1007/s12522-009-0027-8
  35. Yoshida S, Ichinose T, Arashidani K, He M, Takano H et al (2016) Effects of fetal exposure to Asian sand dust on development and reproduction in male offspring. Int J Environ Res Public Health 13:1173. https://doi.org/10.3390/ijerph13111173
  36. Liu B, Wu SD, Shen LJ, Zhao TX, Wei Y et al (2019) Spermatogenesis dysfunction induced by PM2.5 from automobile exhaust via the ROS-mediated MAPK signaling pathway. Ecotoxicol Environ Saf 167:161-168. https://doi.org/10.1016/j.ecoenv.2018.09.118
  37. Sikka SC (2004) Role of oxidative stress and antioxidants in andrology and assisted reproductive technology. J Androl 25:5-18. https://doi.org/10.1002/j.1939-4640.2004.tb02751.x
  38. Palani AF (2018) Effect of serum antioxidant levels on sperm function in infertile male. Mid East Fertil Soc J 23:19-22. https://doi.org/10.1016/j.mefs.2017.07.006
  39. Motawi TM, Sadik NA, Refaat A (2010) Cytoprotective effects of DL-alpha-lipoic acid or squalene on cyclophosphamide-induced oxidative injury: an experimental study on rat myocardium, testicles and urinary bladder. Food Chem Toxicol 48:2326-2336. https://doi.org/10.1016/j.fct.2010.05.067
  40. Liu J, Zhang J, Ren L, Wei J, Zhu Y et al (2019) Fine particulate matters induce apoptosis via the ATM/P53/CDK2 and mitochondria apoptosis pathway triggered by oxidative stress in rat and GC-2spd cell. Ecotoxicol Environ Saf 180:280-287. https://doi.org/10.1016/j.ecoenv.2019.05.013
  41. Wei Y, Cao XN, Tang XL, Shen LJ, Lin T et al (2018) Urban fine particulate matter (PM2.5) exposure destroys blood-testis barrier (BTB) integrity through excessive ROS-mediated autophagy. Toxicol Mech Methods 28:302-319. https://doi.org/10.1080/15376516.2017.1410743
  42. Wang L, Luo D, Liu X, Zhu J, Wang F et al (2021) Effects of PM2.5 exposure on reproductive system and its mechanisms. Chemosphere 264:128436. https://doi.org/10.1016/j.chemosphere.2020.128436
  43. Kaczanowski S (2016) Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging. Phys Biol 13:031001. https://doi.org/10.1088/1478-3975/13/3/031001
  44. Guo H, Ouyang Y, Wang J, Cui H, Deng H et al (2021) Cu-induced spermatogenesis disease is related to oxidative stress-mediated germ cell apoptosis and DNA damage. J Hazard Mater 416:125903. https://doi.org/10.1016/j.jhazmat.2021.125903
  45. Shukla KK, Mahdi AA, Rajender S (2012) Apoptosis, spermatogenesis and male infertility. Front Biosci (Elite Ed) 4:746-754. https://doi.org/10.2741/415
  46. Boekelheide K (2005) Mechanisms of toxic damage to spermatogenesis. J Natl Cancer Inst Monogr 34:6-8. https://doi.org/10.1093/jncimonographs/lgi006
  47. Cai L, Hales BF, Robaire B (1997) Induction of apoptosis in the germ cells of adult male rats after exposure to cyclophosphamide. Biol Reprod 56:1490-1497. https://doi.org/10.1095/biolreprod56.6.1490