Vocational School of Health Sevices, Final International University, Kazafani, Cyprus.
Department of Medical Biochemistry, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik, Turkey.
Mol Biol Rep. 2022 Oct;49(10):9641-9649. doi: 10.1007/s11033-022-07873-5. Epub 2022 Sep 3.
Methotrexate (MT) is a broadly used chemotherapeutic drug however its clinical use is confronted with several forms of toxicities containing testicular damage. The current study assessed the ameliorative effects of morin on MT-induced testicular damage with the investigation of its mechanism and the potential involvement of oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress in such protection.
The animals were divided into 5 distinct groups (7 rats in each group). Group 1 was control group, group 2 received MT-only (20 mg/kg bw), group 3 received orally morin-only (100 mg/kg bw), group 4 received MT (20 mg/kg bw) + morin (50 mg/kg bw) and group 5 received MT (20 mg/kg bw) + morin (100 mg/kg). In this study, morin was administered orally for 10 days, while MT was administered intraperitoneally on the 5th day.
MT intoxication was linked with augmented MDA while decreased GSH levels, the enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase and mRNA levels of HO-1 and Nrf2 in the testis tissues. MT injection caused inflammation in the testicular tissue via up-regulation of MAPK14, NFκB, TNF-α and IL-1β. MT application also caused apoptosis and endoplasmic reticulum stress in the testis tissue via increasing mRNA transcript levels of Bax, caspase-3, PERK, IRE1, ATF-6, GRP78 and down-regulation of Bcl-2.
Treatment with morin at a dose of 50 and 100 mg/kg considerably mitigated oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress in the testicular tissue indicating that testicular damage related to MT toxicity could be modulated by morin administration.
甲氨蝶呤（MT）是一种广泛使用的化疗药物，但在临床应用中面临着多种形式的毒性，包括睾丸损伤。本研究评估了桑色素对 MT 诱导的睾丸损伤的改善作用，并探讨了其机制以及氧化应激、炎症、细胞凋亡和内质网应激在这种保护中的潜在作用。
将动物分为 5 个不同组（每组 7 只大鼠）。第 1 组为对照组，第 2 组仅接受 MT（20mg/kg bw），第 3 组仅接受桑色素（100mg/kg bw），第 4 组接受 MT（20mg/kg bw）+桑色素（50mg/kg bw），第 5 组接受 MT（20mg/kg bw）+桑色素（100mg/kg bw）。在这项研究中，桑色素通过口服给药 10 天，而 MT 通过腹腔注射在第 5 天给药。
MT 中毒与睾丸组织 MDA 增加、GSH 水平降低、谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶的酶活性以及 HO-1 和 Nrf2 的 mRNA 水平降低有关。MAPK14、NFκB、TNF-α 和 IL-1β 的上调导致 MT 注射引起睾丸组织炎症。MT 给药还通过增加 Bax、caspase-3、PERK、IRE1、ATF-6、GRP78 的 mRNA 转录水平和下调 Bcl-2 导致睾丸组织细胞凋亡和内质网应激。
以 50 和 100mg/kg 的剂量用桑色素治疗可显著减轻睾丸组织中的氧化应激、炎症、细胞凋亡和内质网应激，表明桑色素给药可调节与 MT 毒性相关的睾丸损伤。
