Carvacrol alleviates CUMS-induced depressive-like behaviors and cognitive impairment by reducing oxidative stress and neuroinflammation in mice.

The present study aimed to evaluate the protective potential of carvacrol against depressive-like behavior and cognitive impairment prompted by chronic unpredictable mild stress (CUMS) in mice. The animals were divided into six groups: Control (non-stressed), CARV (carvacrol at 50mg/kg, p.o.), FLU (fluoxetine at 10mg/kg, p.o.), CUMS (stressed), CUMS + CARV and CUMS + FLU, and the groups with CUMS were subjected to different stressors for 28 days. After treatment, mice underwent behavioral testing (open field, forced swimming, sucrose preference, social interaction, novel object recognition and Y-maze) and brain areas were removed for oxidative stress (MDA, nitrite/nitrate and GSH levels) and cytokine (IL-1ß and TNF-α) content assays. The results revealed that CARV administration reversed depressive-like behavior and significantly ameliorated the cognitive deficit induced by CUMS, as well as was able to attenuate oxidative stress (decreased MDA and nitrite/nitrate levels and increased GSH levels). In addition, a significant reduction in hippocampal IL-1ß and TNF-α levels was observed, demonstrating a potential anti-neuroinflammatory activity. Taken together, the antioxidant and anti-inflammatory activities observed in this work indicate that CARV is a promising drug for antidepressant treatment.

Cyclooxygenase-2 inhibitors alleviated depressive and anxious-like behaviors in mice exposed to lipopolysaccharide: Involvement of oxidative stress and neuroinflammation.

Depression and anxiety disorders have their pathophysiologies linked to inflammation and oxidative stress. In this context, celecoxib (CLX) and etoricoxib (ETR) inhibit cyclooxygenase 2 (COX-2), an enzyme expressed by cells involved in the inflammatory process and found in the brain. Studies have been using CLX as a possible drug in the treatment of depression, although its mechanisms at the central nervous system level are not fully elucidated. In this study, the effects of CLX and ETR on behavioral, oxidative, and inflammatory changes induced by systemic exposure to Escherichia coli lipopolysaccharide (LPS) were evaluated in adult male swiss mice. For ten days, the animals received intraperitoneal injections of LPS at 0.5 mg/kg. From the sixth to the tenth day, one hour after LPS exposure, they were treated orally with CLX (15 mg/kg), ETR (10 mg/kg), or fluoxetine (FLU) (20 mg/kg). Twenty-four hours after the last oral administration, the animals underwent evaluation of locomotor activity (open field test), predictive tests for depressive-like behavior (forced swim and tail suspension tests), and anxiolytic-like effect (elevated plus maze and hole board tests). Subsequently, the hippocampus, prefrontal cortex and striatum were dissected for the measurement of oxidative and nitrosative parameters (malondialdehyde, nitrite, and glutathione) and quantification of pro-inflammatory cytokines (IL-1ß and IL-6). LPS induced depressive and anxious-like behavior, and treatment with CLX or ETR was able to reverse most of the behavioral changes. It was evidenced that nitrosative stress and the degree of lipid peroxidation induced by LPS were reduced in different brain areas after treatment with the drugs, as well as the endogenous defense system against free radicals was strengthened. CLX and ETR also significantly reduced LPS-induced cytokine levels. These data are expected to expand information on the role of inflammation in depression and anxiety and provide insights into possible mechanisms of COX-2 inhibitors in psychiatric disorders with a neurobiological basis in inflammation and oxidative stress.

Long-term administration of omeprazole in mice: a study of behavior, inflammatory, and oxidative stress alterations with focus on central nervous system.

Chronic use of omeprazole has been linked to central effects alongside with the global concern of increasing appearance of neuropsychiatric disorders. This study aimed to identifying behavioral, inflammatory, and oxidative stress alterations after long-term administration of omeprazole. C57BL/6 mice were divided in groups: OME and Sham, each received either solutions of omeprazole or vehicle, administered for 28 days by gavage. Results observed in the omeprazole-treated mice: Decrease in the crossing parameter in the open field, no change in the motor performance assessed by rotarod, an immobility time reduction in the forced swimming test, improved percentage of correct alternances in the Ymaze and an exploration time of the novel object reduction in the novel object recognition. Furthermore, a reduced weight gain and hippocampal weight were observed. There was an increase in the cytokine IL1-ß levels in both prefrontal cortex (PFC) and serum, whereas TNF-α increased only in the PFC. Nitrite levels increased in the hippocampus (HP) and PFC, while malondialdehyde (MDA) and glutathione (GSH) levels decreased. These findings suggest that omeprazole improves depressive-like behavior and working memory, likely through the increase in nitrite and reduction in MDA levels in PFC and HP, whereas, the impairment of the recognition memory is more likely to be related to the reduced hippocampal weight. The diminished weight gain might be associated with the IL-1ß increased levels in the peripheral blood. Altogether, omeprazole showed to have the potential to impact at central level and inflammatory and oxidative parameters might exert a role between it.