Department of Anatomy, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
J Biochem Mol Toxicol. 2024 Apr;38(4):e23696. doi: 10.1002/jbt.23696.
Although cyclophosphamide (CP) has been approved as an anticancer drug, its toxic effect on most organs, especially the testis, has been established. Piperine (PIP) is an alkaloid that has antioxidant, antiapoptotic, and anti-inflammatory activities. This study was investigated the protective effects of PIP on CP-induced testicular toxicity in the mice. In this experimental study, 48 adult male BALB/c mice (30-35 g) were divided into six groups (n = 8), receiving normal saline (C), 5 mg/kg of PIP (PIP5), 10 mg/kg of PIP (PIP10), 200 mg/kg of CP, 200 mg/kg of CP + PIP5, and 200 mg/kg of CP + PIP10. On the eighth day of the study, blood and testis samples were prepared for serum testosterone hormone quantification, sperm analysis, histological, and immunohistochemical assays. The results of this study showed that CP induced testicular toxicity with the decrease of sperm count, motility, and viability. Also, CP treatment caused histological structure alterations in the testis, including exfoliation, degeneration, vacuolation of spermatogenic cells, and reducing the thickness of the epithelium and the diameter of the seminiferous tubule. In addition, CP decreased glutathione (GSH) levels, increased malondialdehyde (MDA) levels, Caspase-3, and NF-κB. At the same time, PIP treatment reduced testicular histopathological abnormalities, oxidative stress, and apoptosis that were induced by CP. These results showed that PIP improved CP-induced testicular toxicity in mice, which can be related to its antioxidant, antiapoptotic, and anti-inflammatory activities.
尽管环磷酰胺(CP)已被批准为抗癌药物,但它对大多数器官(尤其是睾丸)的毒性作用已得到证实。胡椒碱(PIP)是一种生物碱,具有抗氧化、抗凋亡和抗炎作用。本研究旨在探讨 PIP 对 CP 诱导的小鼠睾丸毒性的保护作用。在这项实验研究中,将 48 只成年雄性 BALB/c 小鼠(30-35g)分为六组(n=8),分别给予生理盐水(C)、5mg/kg PIP(PIP5)、10mg/kg PIP(PIP10)、200mg/kg CP、200mg/kg CP+PIP5 和 200mg/kg CP+PIP10。在研究的第 8 天,采集血清和睾丸样本,用于血清睾酮激素定量、精子分析、组织学和免疫组织化学检测。研究结果表明,CP 可诱导睾丸毒性,导致精子计数、活力和活力降低。此外,CP 处理会导致睾丸组织学结构改变,包括生精细胞脱落、变性、空泡化,以及上皮层和精小管直径变薄。此外,CP 降低了谷胱甘肽(GSH)水平,增加了丙二醛(MDA)水平、Caspase-3 和 NF-κB。同时,PIP 处理可减轻 CP 诱导的睾丸组织病理学异常、氧化应激和凋亡。这些结果表明,PIP 可改善 CP 诱导的小鼠睾丸毒性,这可能与其抗氧化、抗凋亡和抗炎作用有关。