Testicular torsion/detorsion (T/D) is a critical medical condition that necessitates prompt surgical intervention to avoid testicular atrophy and infertility. The use of natural compounds may protect against the associated detrimental oxidative stress and inflammatory responses. Interestingly, acetyl-11-keto-β-boswellic acid (AKBA), the main active constituent of Boswellia resin, has shown potent inhibitory effect on 5-lipoxygenase enzyme which converts arachidonic acid into inflammatory mediators. Therefore, this study was conducted to assess the protective mechanisms by which AKBA may protect against testicular T/D injury in rats. Male rats were randomly distributed into five groups: Sham, AKBA (50 mg/kg, p.o.), unilateral testicular T/D, AKBA at two dose levels (25 or 50 mg/kg for 15 successive days) followed by T/D. Histological examination and Johnsen's score were performed to assess testicular injury and perturbations in spermatogenesis. Biochemical parameters included markers of testicular function (serum testosterone), oxidant/antioxidant status (malondialdehyde, glutathione), inflammation (5-lipoxygenase, leukotriene-B4, myeloperoxidase, interleukin-1β, interleukin-6), apoptosis (Bax, Bcl2, caspase-3), DNA integrity (quantitative DNA fragmentation, DNA laddering, PARP-1), energy production (ATP), in addition to p38 MAPK and JNK protein expression. In a dose dependent manner, AKBA significantly inhibited testicular T/D-induced upregulation of 5-LOX/LTB4 and p38-MAPK/JNK/Bax pathways and their associated downstream inflammatory and apoptotic cascades. These effects were accompanied with ATP replenishment and DNA preservation, resulting ultimately in salvage of the testis. Unprecedentedly, the present mechanistic study revealed the pathways by which AKBA may inhibit testicular T/D injury and offered a novel protective approach that may attenuate the severity of this condition.

中文翻译：

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乙酰-11-酮-β-乳香酸通过调节 5-LOX/LTB4 和 p38-MAPK/JNK/Bax/Caspase-3 通路预防大鼠睾丸扭转/扭转损伤


睾丸扭转/扭转（T/D）是一种危急的医疗状况，需要及时进行手术干预以避免睾丸萎缩和不育。使用天然化合物可以防止相关的有害氧化应激和炎症反应。有趣的是，乳香树脂的主要活性成分乙酰基-11-酮-β-乳香酸（AKBA）对将花生四烯酸转化为炎症介质的5-脂氧合酶具有有效的抑制作用。因此，本研究旨在评估 AKBA 可以防止大鼠睾丸 T/D 损伤的保护机制。雄性大鼠被随机分为五组：假组、AKBA（50 mg/kg，口服）、单侧睾丸 T/D、两个剂量水平的 AKBA（连续 15 天 25 或 50 mg/kg），然后进行 T/D。进行组织学检查和Johnsen评分来评估睾丸损伤和精子发生的扰动。生化参数包括睾丸功能标志物（血清睾酮）、氧化剂/抗氧化状态（丙二醛、谷胱甘肽）、炎症（5-脂氧合酶、白三烯-B4、髓过氧化物酶、白细胞介素-1β、白细胞介素-6）、细胞凋亡（Bax、Bcl2、caspase） -3)、DNA 完整性（定量 DNA 片段化、DNA 阶梯、PARP-1）、能量产生 (ATP)，以及 p38 MAPK 和 JNK 蛋白表达。 AKBA 以剂量依赖性方式显着抑制睾丸 T/D 诱导的 5-LOX/LTB4 和 p38-MAPK/JNK/Bax 通路及其相关的下游炎症和细胞凋亡级联的上调。这些效应伴随着 ATP 补充和 DNA 保存，最终挽救了睾丸。 目前的机制研究前所未有地揭示了 AKBA 抑制睾丸 T/D 损伤的途径，并提供了一种新的保护方法，可以减轻这种情况的严重性。