Temnik Max, Gurin Sergey, Balakin Alexandr, Byshovets Roman, Kalmukova Olesia, Vovk Tetiana, Halenova Tetiana, Raksha Nataliia, Falalyeyeva Tetyana, Savchuk Olexiy
Physical Chemistry, Vector Vitale, North Miami Beach, Florida, United States.
Department of Internal Diseases, Bogomolets National Medical University, Kyiv, Ukraine.
Front Pharmacol. 2025 May 16;16:1543166. doi: 10.3389/fphar.2025.1543166. eCollection 2025.
Zinc is a critical micronutrient that plays multifaceted roles in oxidative stress management, lipid metabolism, pancreatic function, and liver health, which are all closely interconnected with obesity. Maintaining adequate zinc levels is essential for overall metabolic health and proper functioning of these vital systems. The investigational new drug complex of zinc-64 aspartate (KLS-1 or Zn-aspartate) was evaluated in this study as a pharmaceutical agent targeting oxidative stress and lipid metabolism using rodent model of obesity. KLS-1 is the isotopically modified zinc aspartate in which stable (non-radioactive) Zn atoms were enriched to exceed 99% atomic fraction of total zinc, as compared to natural isotopic ratio of 64Zn of 48.6%. In this paper, we discuss our findings and the effects rendered by KLS-1 on lipid metabolism, pancreas and liver function. This study was conducted on outbred rats, which were divided into four experimental groups: 1) the control group consuming standard food (3.81 kcal/g), 2) the obese group consuming a high-calorie diet (5.35 kcal/g), 3) the obese group consuming a high-calorie diet (5.35 kcal/g) treated with intragastric administration of Zn- aspartate at a dose of 4.5 mg per animal during 6 weeks (the ), 4) the group consuming standard food diet (3.81 kcal/g) with Zn- aspartate form administration. The obese rats treated with Zn-64 stable isotope demonstrated decreased area of the hepatocytes, insulin and glucose levels in serum; increased catalase and superoxide dismutase activity, and area of pancreatic islets in comparison with the obese group. The study shows that Zn-aspartate is effective as a therapeutic agent for obesity management, significantly reducing body mass, improving histopathological changes in the pancreas and liver and normalizing oxidative stress in high-calorie diet animal models. These findings suggest that Zn- aspartate may be a promising monotherapy or adjunct treatment for obesity, offering benefits in weight reduction, organ protection, and antioxidant balance.
锌是一种关键的微量营养素，在氧化应激管理、脂质代谢、胰腺功能和肝脏健康中发挥多方面作用，而这些方面均与肥胖密切相关。维持充足的锌水平对于整体代谢健康以及这些重要系统的正常运作至关重要。本研究使用肥胖啮齿动物模型，对新型研究药物天冬氨酸锌-64（KLS-1或锌-天冬氨酸）作为一种针对氧化应激和脂质代谢的药物制剂进行了评估。KLS-1是同位素修饰的天冬氨酸锌，其中稳定（非放射性）锌原子的富集量超过总锌原子分数的99%，而天然64Zn的同位素比率为48.6%。在本文中，我们讨论了我们的研究结果以及KLS-1对脂质代谢、胰腺和肝脏功能的影响。本研究以远交系大鼠为实验对象，将其分为四个实验组：1）食用标准食物（3.81千卡/克）的对照组；2）食用高热量饮食（5.35千卡/克）的肥胖组；3）在6周内以每只动物4.5毫克的剂量通过胃内给药天冬氨酸锌进行治疗的食用高热量饮食（5.35千卡/克）的肥胖组（该组）；4）以天冬氨酸锌形式给药的食用标准食物饮食（3.81千卡/克）的组。与肥胖组相比，用锌-64稳定同位素治疗的肥胖大鼠肝细胞面积、血清胰岛素和葡萄糖水平降低；过氧化氢酶和超氧化物歧化酶活性以及胰岛面积增加。该研究表明，天冬氨酸锌作为一种治疗肥胖的药物有效，在高热量饮食动物模型中可显著减轻体重、改善胰腺和肝脏的组织病理学变化并使氧化应激正常化。这些发现表明，天冬氨酸锌可能是一种有前景的肥胖单一疗法或辅助治疗方法，在减轻体重、器官保护和抗氧化平衡方面具有益处。
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