Cerium Oxide Nanoparticles Protect Cyclophosphamide-induced Testicular Toxicity in Mice

Overview

Journal Int J Prev Med

Date 2019 Feb 19

PMID 30774839

Citations 17

Authors

Maedeh Hamzeh

Seyed Jalal Hosseinimehr

Abbasali Karimpour

Hamid Reza Mohammadi

Ali Reza Khalatbary

Fereshteh Talebpour Amiri

Affiliations

Soon will be listed here.

Abstract

Background: Cyclophosphamide (CP), as a chemotherapy drug, causes severe damage in testicular tissue through producing free radicals. Cerium oxide nanoparticles (NC) exhibit antioxidant and anti-inflammatory properties. The purpose of this study was to investigate the protective effect of NC on CP-induced testicular damage in mice.

Methods: In this experimental study, thirty-two male mice were divided into four groups (eight mice in each group). The control group was received intraperitoneally (IP) normal saline, NC group was received NC for three consecutive days (100 μg/kg, IP), CP group was received CP (200 mg/kg, IP), and the CP + NC group received NC, three consecutive days before receiving CP. After 2 days, testicles were assessed for biochemical, histomorphometrical, histopathological, and immunohistochemical analyses.

Results: CP administration caused statistically significant increases in sperm abnormality, malondialdehyde, protein carbonyl levels, reactive oxygen species, level and apoptosis, and decreases in sperm count, sperm viability, testosterone, glutathione activity, the mean thickness of the germinal epithelium, diameter of seminiferous tubules in mice. Degeneration, necrosis, arrest of spermatogenesis, congestion, and atrophy in testicular tissue confirmed the low Johnsen's Testicular score in CP group. Administration of NC significantly ameliorated the CP-induced adverse effects on testis compared with the CP group. In addition, pretreatment mice with NC significantly reduced caspase-3 immunoreactivity induced by CP in testis.

Conclusions: This study showed that NC with scavenging free radicals and antiapoptotic properties enable to reduce the side effects of CP in the testicular tissue.

Citing Articles

The protection afforded by kefir against cyclophosphamide induced testicular toxicity in rats by oxidant antioxidant and histopathological evaluations.

Yildiz S, Demir C, Cengiz M, Irmak H, Peker Cengiz B, Ayhanci A Sci Rep. 2024; 14(1):18463.

PMID: 39122852 PMC: 11316007. DOI: 10.1038/s41598-024-67982-y.

Alkylating agents-induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front.

Sriram S, Macedo T, Mavinkurve-Groothuis A, van de Wetering M, Looijenga L Clin Transl Sci. 2024; 17(7):e13866.

PMID: 38965809 PMC: 11224131. DOI: 10.1111/cts.13866.

Preventive effects of quercetin against inflammation and apoptosis in cyclophosphamide-induced testicular damage.

Uzun-Goren D, Uz Y Iran J Basic Med Sci. 2024; 27(5):647-656.

PMID: 38629094 PMC: 11017851. DOI: 10.22038/IJBMS.2024.74458.16177.

Radioprotective Potency of Nanoceria.

Alvandi M, Shaghaghi Z, Farzipour S, Marzhoseyni Z Curr Radiopharm. 2023; 17(2):138-147.

PMID: 37990425 DOI: 10.2174/0118744710267281231104170435.

Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats.

Khamis T, Awad Hegazy A, El-Fatah S, Abdelfattah E, Abdelfattah M, Fericean L Pharmaceuticals (Basel). 2023; 16(2).

PMID: 37259444 PMC: 9966503. DOI: 10.3390/ph16020301.

References

Howell S, Radford J, Ryder W, Shalet S . Testicular function after cytotoxic chemotherapy: evidence of Leydig cell insufficiency. J Clin Oncol. 1999; 17(5):1493-8. DOI: 10.1200/JCO.1999.17.5.1493. View

Ghosh D, Das U, Ghosh S, Mallick M, Debnath J . Testicular gametogenic and steroidogenic activities in cyclophosphamide treated rat: a correlative study with testicular oxidative stress. Drug Chem Toxicol. 2002; 25(3):281-92. DOI: 10.1081/dct-120005891. View

Skorodumova N, Simak S, Lundqvist B, Abrikosov I, Johansson B . Quantum origin of the oxygen storage capability of ceria. Phys Rev Lett. 2002; 89(16):166601. DOI: 10.1103/PhysRevLett.89.166601. View

Arenas M, Lobo M, Caso E, Huerta L, Paniagua R, Martin-Hidalgo M . Normal and pathological human testes express hormone-sensitive lipase and the lipid receptors CLA-1/SR-BI and CD36. Hum Pathol. 2004; 35(1):34-42. DOI: 10.1016/j.humpath.2003.08.015. View

LEAR L, Nation R, Stupans I . Effects of cyclophosphamide and adriamycin on rat hepatic microsomal glucuronidation and lipid peroxidation. Biochem Pharmacol. 1992; 44(4):747-53. DOI: 10.1016/0006-2952(92)90412-c. View

Vernet P, Aitken R, Drevet J . Antioxidant strategies in the epididymis. Mol Cell Endocrinol. 2004; 216(1-2):31-9. DOI: 10.1016/j.mce.2003.10.069. View

Sen Gupta R, Kim J, Gomes C, Oh S, Park J, Im W . Effect of ascorbic acid supplementation on testicular steroidogenesis and germ cell death in cadmium-treated male rats. Mol Cell Endocrinol. 2004; 221(1-2):57-66. DOI: 10.1016/j.mce.2004.03.012. View

Niu J, Azfer A, Rogers L, Wang X, Kolattukudy P . Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc Res. 2007; 73(3):549-59. PMC: 1855085. DOI: 10.1016/j.cardiores.2006.11.031. View

Agarwal A, Makker K, Sharma R . Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol. 2007; 59(1):2-11. DOI: 10.1111/j.1600-0897.2007.00559.x. View

10.

Park E, Choi J, Park Y, Park K . Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells. Toxicology. 2008; 245(1-2):90-100. DOI: 10.1016/j.tox.2007.12.022. View

11.

Hirst S, Karakoti A, Tyler R, Sriranganathan N, Seal S, Reilly C . Anti-inflammatory properties of cerium oxide nanoparticles. Small. 2009; 5(24):2848-56. DOI: 10.1002/smll.200901048. View

12.

Colon J, Hsieh N, Ferguson A, Kupelian P, Seal S, Jenkins D . Cerium oxide nanoparticles protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2. Nanomedicine. 2010; 6(5):698-705. DOI: 10.1016/j.nano.2010.01.010. View

13.

Ceribasi A, Turk G, Sonmez M, Sakin F, Atessahin A . Toxic effect of cyclophosphamide on sperm morphology, testicular histology and blood oxidant-antioxidant balance, and protective roles of lycopene and ellagic acid. Basic Clin Pharmacol Toxicol. 2010; 107(3):730-6. DOI: 10.1111/j.1742-7843.2010.00571.x. View

14.

Turk G, Ceribasi A, Sakin F, Sonmez M, Atessahin A . Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis. Reprod Fertil Dev. 2010; 22(4):587-96. DOI: 10.1071/RD09078. View

15.

Celardo I, Pedersen J, Traversa E, Ghibelli L . Pharmacological potential of cerium oxide nanoparticles. Nanoscale. 2011; 3(4):1411-20. DOI: 10.1039/c0nr00875c. View

16.

Estevez A, Pritchard S, Harper K, Aston J, Lynch A, Lucky J . Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radic Biol Med. 2011; 51(6):1155-63. DOI: 10.1016/j.freeradbiomed.2011.06.006. View

17.

Singh A, Lange T, Kim K, Brard L, Horan T, Moore R . Purified cranberry proanthocyanidines (PAC-1A) cause pro-apoptotic signaling, ROS generation, cyclophosphamide retention and cytotoxicity in high-risk neuroblastoma cells. Int J Oncol. 2011; 40(1):99-108. DOI: 10.3892/ijo.2011.1225. View

18.

Pagliari F, Mandoli C, Forte G, Magnani E, Pagliari S, Nardone G . Cerium oxide nanoparticles protect cardiac progenitor cells from oxidative stress. ACS Nano. 2012; 6(5):3767-75. DOI: 10.1021/nn2048069. View

19.

Abarikwu S, Otuechere C, Ekor M, Monwuba K, Osobu D . Rutin Ameliorates Cyclophosphamide-induced Reproductive Toxicity in Male Rats. Toxicol Int. 2012; 19(2):207-14. PMC: 3388768. DOI: 10.4103/0971-6580.97224. View

20.

Das S, Singh S, Dowding J, Oommen S, Kumar A, Sayle T . The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials. 2012; 33(31):7746-55. PMC: 4590782. DOI: 10.1016/j.biomaterials.2012.07.019. View