Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka, Nigeria.
Biomed Pharmacother. 2022 Jun;150:113056. doi: 10.1016/j.biopha.2022.113056. Epub 2022 May 1.
Testicular ischaemia/reperfusion (I/R) injury is a major consequence of testicular torsion with possible attendant risk of male infertility. Glutamine, on the other hand, is a known antioxidant with anti-inflammatory potential. The present study evaluated whether or not glutamine would improve I/R-induced testicular injury in torsion/detorsion (T/D). The possible associated mechanisms were also investigated.
Wistar rats were randomly allotted into four groups (n = 10); sham-operated, glutamine-treated, T/D, and T/D + glutamine. Testicular torsion was induced and reperfusion established after two and a half hour under ketamine/xylazine anaethesia. Glutamine was administered one hour before reperfusion and continued daily for 3 days. At the end of the study, animals were euthanized, blood samples obtained, epididymal sperm suspension collected, and the testes harvested for biochemical and histopathological assays using established methods.
Glutamine prevented T/D-driven I/R-induced reduced sperm quality, impaired testicular histoarchitecture, and suppressed circulating testosterone. Also, glutamine abated I/R-induced oxidative stress (evidenced by reduced hydrogen peroxide and MDA generation and enhanced concentrations and activities of antioxidants), inflammation (evidenced by suppression of TNF-α and IL-1β), and apoptosis (evidenced by reduced DNA fragmentation) by down-regulating NF-kB and caspase 3 activity.
For the first time, this study demonstrated that glutamine administration improved testicular I/R injury in T/D rat model by maintaining testicular redox balance, and testicular integrity and function via inhibition of I/R-induced upregulation of NF-kB signaling and caspase 3 activation.
睾丸缺血/再灌注(I/R)损伤是睾丸扭转的主要后果,可能伴有男性不育的风险。另一方面,谷氨酰胺是一种已知的抗氧化剂,具有抗炎潜力。本研究评估了谷氨酰胺是否会改善扭转/复位(T/D)引起的 I/R 睾丸损伤。还研究了可能的相关机制。
将 Wistar 大鼠随机分为四组(n=10);假手术、谷氨酰胺治疗、T/D 和 T/D+谷氨酰胺。在氯胺酮/甲苯噻嗪麻醉下诱导睾丸扭转,2.5 小时后恢复灌注。谷氨酰胺在再灌注前 1 小时给药,并连续给药 3 天。研究结束时,处死动物,采集血液样本,收集附睾精子悬液,并采集睾丸进行生化和组织病理学检测,方法如下。
谷氨酰胺预防了 T/D 引起的 I/R 诱导的精子质量下降、睾丸组织形态结构受损和循环睾酮水平降低。此外,谷氨酰胺减轻了 I/R 引起的氧化应激(表现为减少过氧化氢和 MDA 的产生,增加抗氧化剂的浓度和活性)、炎症(表现为 TNF-α和 IL-1β的抑制)和凋亡(表现为 DNA 片段化减少),通过下调 NF-kB 和 caspase 3 的活性。
本研究首次表明,谷氨酰胺给药通过维持睾丸氧化还原平衡和睾丸完整性和功能,改善 T/D 大鼠模型中的睾丸 I/R 损伤,抑制 I/R 诱导的 NF-kB 信号转导和 caspase 3 激活。