Laboratório de Biomarcadores, Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil.
Laboratório de Neuroquímica, Inflamação e Câncer, Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil.
Biochem Biophys Res Commun. 2024 Nov 19;734:150635. doi: 10.1016/j.bbrc.2024.150635. Epub 2024 Aug 30.
This study explores the therapeutic benefits of tannic acid (TnA) in an experimental protocol of chronic hypermethioninemia in rats. Rats were categorized into four groups: Group I - control, Group II - TnA 30 mg/kg, Group III - methionine (Met) 0.2-0.4 g/kg + methionine sulfoxide (MS) 0.05-0.1 g/kg, Group IV - TnA/Met + MS. Saline was administered by subcutaneous pathway into groups I and II twice daily from postnatal day 6 (P6) to P28, whereas those in groups III and IV received Met + MS. From P28 to P35, groups II and IV received TnA orally. Animals from group III presented cognitive and memory impairment assessed through object recognition and Y-maze tests (p < 0.05). Elevated levels of reactive species, lipid peroxidation, and nitrites followed by a decline in sulfhydryl content, catalase activity, and superoxide dismutase activity were observed in animals treated with Met + MS (p < 0.05). However, TnA treatment reversed all these effects (p < 0.05). In group III, there was an increase in acetylcholinesterase activity and IL-6 levels, coupled with a reduction in Na/K-ATPase activity (p < 0.05). TnA was able to protect against these effects (p < 0.05). The gene expression of catalase, brain-derived neurotrophic factor, and nuclear factor erythroid 2-related factor 2 was decreased in the hippocampus and striatum from group III (p < 0.05). TnA reversed almost all of these alterations (p < 0.05). These findings suggest that TnA is a therapeutic target for patients with hypermethioninemia.
本研究探讨了单宁酸（TnA）在慢性高蛋氨酸血症大鼠实验方案中的治疗益处。大鼠分为四组：I 组 - 对照组，II 组 - TnA 30mg/kg，III 组 - 蛋氨酸（Met）0.2-0.4g/kg+蛋氨酸亚砜（MS）0.05-0.1g/kg，IV 组 - TnA/Met+MS。I 组和 II 组通过皮下途径每天两次给予生理盐水，从出生后第 6 天（P6）到 P28，而 III 组和 IV 组给予 Met+MS。从 P28 到 P35，II 组和 IV 组口服 TnA。III 组动物表现出认知和记忆障碍，通过物体识别和 Y 迷宫测试评估（p<0.05）。用 Met+MS 处理的动物观察到活性物质、脂质过氧化和亚硝酸盐水平升高，随后巯基含量、过氧化氢酶活性和超氧化物歧化酶活性下降（p<0.05）。然而，TnA 处理逆转了所有这些影响（p<0.05）。在 III 组中，乙酰胆碱酯酶活性和 IL-6 水平增加，同时 Na/K-ATP 酶活性降低（p<0.05）。TnA 能够防止这些影响（p<0.05）。III 组海马体和纹状体中过氧化氢酶、脑源性神经营养因子和核因子红细胞 2 相关因子 2 的基因表达降低（p<0.05）。TnA 逆转了几乎所有这些改变（p<0.05）。这些发现表明 TnA 是高蛋氨酸血症患者的治疗靶点。
