Cobos-Puc Luis E, Aguayo-Morales Hilda
Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Boulevard Venustiano Carranza S/N Esq. Con Ing. José Cárdenas Valdés, República Oriente, Saltillo 25280, Mexico.
Antioxidants (Basel). 2025 Jul 8;14(7):837. doi: 10.3390/antiox14070837.
Cognitive decline is a common complication of diabetes mellitus, driven in part by oxidative stress and impaired glucose-insulin homeostasis. This study examined the neuroprotective effects of agmatine (200 mg/kg intraperitoneally) in female BALB/c diabetic mice. Several receptor pathways were examined using commercially available antagonists. Behavioral performance was evaluated using the novel object recognition test. Metabolic parameters, such as glucose and insulin levels, as well as antioxidants, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), were measured in blood and brain tissue. The diabetic mice exhibited impaired recognition memory (discrimination index = 0.08), hyperglycemia (24.3 mmol/L), decreased insulin levels (38.4 µU/mL), and diminished antioxidant defenses (CAT: 75.4 U/g tissue, SOD: 32.6 U/g tissue, and GSH: 8.3 mmol/g tissue). Agmatine treatment improved cognitive function and reversed the biochemical alterations. However, these effects were reduced when agmatine was co-administered with imidazoline I/I receptor antagonists. Correlation analysis revealed that cognitive performance positively correlated with antioxidant enzyme levels and insulin levels and negatively correlated with glucose concentrations. Strong intercorrelations among CAT, SOD, and GSH levels suggest a coordinated antioxidant response. Overall, these results imply that agmatine's neuroprotective effects are partially mediated by modulation of the oxidative balance and glucose-insulin regulation via imidazoline receptors.
认知功能衰退是糖尿病的常见并发症，部分由氧化应激和葡萄糖 - 胰岛素稳态受损所致。本研究检测了胍丁胺（200毫克/千克，腹腔注射）对雌性BALB/c糖尿病小鼠的神经保护作用。使用市售拮抗剂检测了几种受体途径。通过新颖物体识别试验评估行为表现。测量了血液和脑组织中的代谢参数，如葡萄糖和胰岛素水平，以及抗氧化剂，包括过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）。糖尿病小鼠表现出识别记忆受损（辨别指数 = 0.08）、高血糖（24.3毫摩尔/升）、胰岛素水平降低（38.4微单位/毫升）以及抗氧化防御能力减弱（CAT：75.4单位/克组织，SOD：32.6单位/克组织，GSH：8.3毫摩尔/克组织）。胍丁胺治疗改善了认知功能并逆转了生化改变。然而，当胍丁胺与咪唑啉I/I受体拮抗剂联合给药时，这些作用减弱。相关性分析显示，认知表现与抗氧化酶水平和胰岛素水平呈正相关，与葡萄糖浓度呈负相关。CAT、SOD和GSH水平之间的强相互相关性表明存在协同的抗氧化反应。总体而言，这些结果表明胍丁胺的神经保护作用部分是通过咪唑啉受体调节氧化平衡和葡萄糖 - 胰岛素调节介导的。
