The antioxidant and anti-proinflammatory activities of l-leucine were investigated on oxidative testicular injury, ex vivo. In vitro analysis revealed l-leucine to be a potent scavenger of free radicals, while inhibiting acetylcholinesterase activity. Oxidative injury was induced in testicular tissues using FeSO₄. Treatment with l-leucine led to depletion of oxidative-induced elevated levels of NO, MDA, and myeloperoxidase activity, with concomitant elevation of reduced glutathione and non-protein thiol levels, SOD and catalase activities. l-leucine caused a significant (p < 0.05) alteration of oxidative-elevated acetylcholinesterase and chymotrypsin activities, while concomitantly elevating the activities of ATPase, ENTPDase and 5′-nucleotidase. l-leucine conferred a protective effect against oxidative induced DNA damage. Molecular docking revealed molecular interactions with COX-2, IL-1 beta and iNOS. Treatment with l-leucine led to restoration of oxidative depleted ascorbic acid-2-sulfate, with concomitant depletion of the oxidative induced metabolites: D-4-Hydroxy-2-oxoglutarate, l-cystine, adenosine triphosphate, maleylacetoacetic acid, cholesteryl ester, and 6-Hydroxy flavin adenine dinucleotide. Treatment with l-leucine reactivated glycolysis while concomitantly deactivating oxidative-induced citrate cycle and increasing the impact-fold of purine metabolism pathway. l-leucine was predicted not to be an inhibitor of CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, with a predicted LD₅₀ value of 5000 mg/Kg and toxicity class of 5. Additionally, l-leucine showed little or no in vitro cytotoxicity in mammalian cells. These results suggest the therapeutic potentials of l-leucine on oxidative testicular injury, as evident by its ability to attenuate oxidative stress and proinflammation, while stalling cholinergic dysfunction and modulating nucleotide hyrolysis; as well as modulate oxidative dysregulated metabolites and their pathways.

在离体氧化睾丸损伤中研究了l-亮氨酸的抗氧化和抗炎活性。体外分析显示l-亮氨酸是一种有效的自由基清除剂，同时抑制乙酰胆碱酯酶活性。使用FeSO ₄在睾丸组织中诱导氧化损伤。用l-亮氨酸处理导致氧化诱导的 NO、MDA 和髓过氧化物酶活性升高的消耗，伴随着降低的谷胱甘肽和非蛋白硫醇水平、SOD 和过氧化氢酶活性的升高。l -亮氨酸引起显着（p < 0.05) 改变氧化升高的乙酰胆碱酯酶和胰凝乳蛋白酶的活性，同时提高 ATPase、ENTPDase 和 5'-核苷酸酶的活性。l-亮氨酸对氧化诱导的DNA损伤具有保护作用。分子对接揭示了与 COX-2、IL-1 beta 和 iNOS 的分子相互作用。用l-亮氨酸处理导致氧化消耗的抗坏血酸-2-硫酸盐的恢复，伴随氧化诱导的代谢物的消耗：D-4-羟基-2-氧戊二酸、l-胱氨酸、三磷酸腺苷、马来酰乙酰乙酸、胆固醇酯、和6-羟基黄素腺嘌呤二核苷酸。用l处理-亮氨酸重新激活糖酵解，同时使氧化诱导的柠檬酸循环失活并增加嘌呤代谢途径的影响倍数。预计l-亮氨酸不是 CYP1A2、CYP2C19、CYP2C9、CYP2D6 和 CYP3A4 的抑制剂，预计 LD ₅₀值为 5000 mg/Kg，毒性等级为 5。此外，l-亮氨酸在体外显示很少或没有哺乳动物细胞中的细胞毒性。这些结果表明l-亮氨酸对氧化性睾丸损伤具有治疗潜力，这体现在其减弱氧化应激和促炎症的能力，同时阻止胆碱能功能障碍和调节核苷酸水解；以及调节氧化失调的代谢物及其途径。