The antioxidant gallic acid induces anxiolytic-, but not antidepressant-like effect, in streptozotocin-induced diabetes

Abstract

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.

Aerobic exercise has an anxiolytic effect on streptozotocin-induced diabetic rats

“…Streptozotocin (STZ) is the most common drug used in experimental diabetes (Radenkovic et al, 2016). STZ-induced diabetes aggravates anxiety-like behaviors (ALB) (Thorre et al, 1997;Aksu et al, 2012;Tang et al, 2015;Rajashree et al, 2017;Aswar et al, 2017;Pereira et al, 2018;Rahmani et al, 2018;Rajabi et al, 2018), depression-like behaviors (DLB) (da Silva Haeser et al, 2007;Gupta et al, 2014;Aswar et al, 2017;Rebolledo-Solleiro and Fernandez-Guasti, 2018), and cognitive deficits (CD) (Zhou et al, 2015;Sun et al, 2017;Gocmez et al, 2019) in rodents. Hilakivi-Clarke et al (1990) reported that male (Swiss NIH) diabetic mice exhibited less social interaction and more aggressive behaviors in the resident-intruder test.…”

Gallic acid improves recognition memory and decreases oxidative‐inflammatory damage in the rat hippocampus with metabolic syndrome

“…However, GA administration seems to fix and prevent the damage caused by these conditions, since treatment with GA decreased oxidative stress and improved antioxidant enzyme activity in the hippocampus of rats with MS. Previous studies with GA have demonstrated its neuroprotective effects in a rat model of streptozotocin-induced T2D (Pereira et al, 2018), preventing degeneration and neuronal death of the hippocampus. The neuroprotective effect was associated with the elimination of free radicals, deactivating the enzymes responsible for the production of ROS, and promoting positive regulation of SOD and CAT (Saibabu, Fatima, Khan, & Hameed, 2015;Thyagaraju, 2008).…”

“…In MS and obesity models, there is evidence that GA improves the plasma concentrations of triglyceride and glucose, as well as a recovery of glucose tolerance and lipid metabolism (Bak et al., 2013; Chao et al., 2014; Dludla et al., 2018; Schimites et al., 2020). In animal models, anxiolytic, antidepressant, and antiepileptic effects have also been observed (Can, Turan, Demir Ozkay, & Ozturk, 2017; Pereira et al., 2018). However, there is still not enough information regarding its impact on the brain.…”

Natural Compounds as Medical Strategies in the Prevention and Treatment of Psychiatric Disorders Seen in Neurological Diseases

“…Gallic acid treatment was capable to generate an anxiolytic-like activity in the EPM and light-dark transition (LDT) tests, but not antidepressant-like effect in the FST. Also, oxidative stress in the rat hippocampus and prefrontal cortex was reversed with gallic acid via decreasing lipid peroxidation and increasing reduced GSH ( Pereira et al, 2018 ).…”