Hamzeh Maedeh, Hosseinimehr Seyed Jalal, Karimpour Abbasali, Mohammadi Hamid Reza, Khalatbary Ali Reza, Talebpour Amiri Fereshteh
Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Anatomy, Faculty of Medicine, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Int J Prev Med. 2019 Jan 15;10:5. doi: 10.4103/ijpvm.IJPVM_184_18. eCollection 2019.
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.
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.
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.
This study showed that NC with scavenging free radicals and antiapoptotic properties enable to reduce the side effects of CP in the testicular tissue.
环磷酰胺(CP)作为一种化疗药物,通过产生自由基对睾丸组织造成严重损伤。氧化铈纳米颗粒(NC)具有抗氧化和抗炎特性。本研究旨在探讨NC对CP诱导的小鼠睾丸损伤的保护作用。
在本实验研究中,32只雄性小鼠分为四组(每组8只)。对照组腹腔注射生理盐水,NC组连续三天腹腔注射NC(100μg/kg),CP组腹腔注射CP(200mg/kg),CP+NC组在注射CP前连续三天腹腔注射NC。2天后,对睾丸进行生化、组织形态计量学、组织病理学和免疫组织化学分析。
CP给药导致小鼠精子异常率、丙二醛、蛋白质羰基水平、活性氧水平和凋亡率显著升高,精子计数、精子活力、睾酮、谷胱甘肽活性、生精上皮平均厚度、曲细精管直径显著降低。睾丸组织的变性、坏死、生精停滞、充血和萎缩证实了CP组较低的约翰森睾丸评分。与CP组相比,NC给药显著改善了CP对睾丸的不良影响。此外,NC预处理小鼠显著降低了CP诱导的睾丸中caspase-3免疫反应性。
本研究表明,具有清除自由基和抗凋亡特性的NC能够减轻CP对睾丸组织的副作用。