Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Rua Coronel H dos Santos S/N, P.O. Box 19031, Curitiba-PR, 81540-990, Brazil.
Departamento de Química, Universidade Federal de São Carlos, Rodovia Washington Luís, Km 235 CP 676, São Carlos, SP, CEP 13565-905, Brazil.
Metab Brain Dis. 2018 Oct;33(5):1573-1584. doi: 10.1007/s11011-018-0264-9. Epub 2018 Jun 23.
The physiopathology of anxiety or depression related to diabetes is still poorly understood. The treatment with antidepressant drugs is a huge challenge due to theirs adherence low rate and many adverse effects. Thus, the seeking for a better treatment for these associated diseases is of utmost importance. Given that the oxidative stress in different tissues occurs in diabetes and anxiety or depression as well, the antioxidant gallic acid becomes an interesting compound to be investigated. Thus, the effects of long-term treatment with gallic acid (0, 10, 20 and 40 mg/kg; gavage) were evaluated in diabetic (DBT) animals submitted to the elevated plus-maze (EPM), the light-dark transition (LDT) tests and modified forced swim test (mFST). Also, indirect parameters of oxidative stress, lipid peroxidation (LPO) and reduced glutathione (GSH) levels were evaluated in the hippocampus (HIP) and prefrontal cortex (PFC). The results showed that DBT animals presented a decrease in the spent time in the open arms, in the end arm exploration and head dips when evaluated in the EPM test; moreover, a decrease in the spent time in the lit compartment of LDT test was observed, suggesting an anxiogenic-like behavior. During the mFST, an increase in the mean counts of immobility and a decrease in the mean counts of swimming and climbing were observed, indicating a depressive-like behavior. These aversive behaviors were more pronounced when compared to normoglycemic (NGL) animals and streptozotocin-treated animals that not become DBT. In addition, DBT rats showed an increase in the oxidative stress parameters in the HIP and PFC that was reversed by the gallic acid treatment (lowest dose - 10 mg/kg), i.e., the treatment decreased the elevated LPO levels and increased the reduced GSH in the HIP and PFC. Also, gallic acid treatment was able to produce an anxiolytic-like effect in the EPM and LDT tests, but not antidepressant-like effect in the FST. Taken together, the results suggest that the antioxidant/neuroprotective effect of gallic acid treatment in HIP and PFC of DBT animals may be essential to the anxiolytic-like effect.
焦虑或抑郁与糖尿病相关的病理生理学仍知之甚少。由于抗抑郁药的依从性低和许多不良反应，用抗抑郁药治疗是一个巨大的挑战。因此，寻找这些相关疾病的更好治疗方法至关重要。鉴于不同组织中的氧化应激在糖尿病以及焦虑或抑郁中也会发生，抗氧化剂没食子酸成为一个值得研究的有趣化合物。因此，长期用没食子酸（0、10、20 和 40mg/kg；灌胃）治疗糖尿病（DBT）动物，然后评估其在高架十字迷宫（EPM）、明暗过渡（LDT）测试和改良强迫游泳测试（mFST）中的效果。此外，还评估了海马（HIP）和前额叶皮层（PFC）中氧化应激的间接参数，即脂质过氧化（LPO）和还原型谷胱甘肽（GSH）水平。结果显示，DBT 动物在 EPM 测试中，进入开放臂的时间减少，末端臂探索和头部浸入减少；此外，LDT 测试中进入亮区的时间减少，提示焦虑样行为。在 mFST 中，观察到不动时间的平均值增加和游泳和攀爬时间的平均值减少，表明出现抑郁样行为。与正常血糖（NGL）动物和未发展为 DBT 的链脲佐菌素处理动物相比，这些负面行为更为明显。此外，DBT 大鼠的 HIP 和 PFC 中的氧化应激参数增加，而用没食子酸治疗（最低剂量-10mg/kg）则逆转了这些参数，即治疗降低了升高的 LPO 水平，并增加了 HIP 和 PFC 中的还原型 GSH。此外，没食子酸治疗能够在 EPM 和 LDT 测试中产生类似抗焦虑的效果，但在 FST 中没有抗抑郁的效果。综上所述，结果表明，没食子酸治疗在 DBT 动物的 HIP 和 PFC 中的抗氧化/神经保护作用可能对类似抗焦虑的效果至关重要。
