The long-term treatment of mice with D-galactose (D-gal) induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. Calcium dobesilate (CaD, Doxium®) is an established vasoactive and angioprotective drug commonly used for the clinical treatment of diabetic retinopathy and chronic venous insufficiency. It has antioxidant properties and controls vascular permeability. In the current study, we evaluated the protective effects of CaD (50 and 100 mg/kg/day p.o.) in male mice treated with D-gal (500 mg/kg/day p.o.) for six weeks. Results demonstrated that body weight loss, anxiety-like and cognitive impairments of D-gal-treated animals were reversed by CaD administration as evaluated by the measurement of mice performance in elevated plus-maze, Y-maze, and shuttle box tests. CaD treatment also inhibited the oxidative stress in aging mouse brains by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities. These results could open new perspectives for the clinical use of CaD in treating and preventing cognitive impairment in older people.
Objective Post-traumatic stress disorder (PTSD) and chronic pain often co-occur. Studies have shown an interaction between pain and PTSD. In this narrative review, we aim to support conducting comprehensive studies by describing PTSD, pain and determining whether opioidergic system, its agonist and antagonist manipulation could positively or negatively affect PTSD symptoms and concurrent pain.Methods Term searches was done in Google Scholar, Scopus, ScienceDirect, Web of Science and PubMed databases as well as hand searching in key resource journals from 1979–2019.Results There are a lot of contradictions and disputes when endogenous opioidergic system and opioidergic antagonist system are studied in PTSD patients. Exogenous morphine administration in PTSD patients can decrease the symptoms of PTSD but it doesn’t have a pain reduction effect to an acceptable level. Beta-endorphin as an endogenous opioid is effective in pain reduction in the moment of events but after minutes to hours, the endorphins withdrawal syndrome leads to exaggerated intrusive thoughts and flashbacks of PTSD, which exacerbate the pain. It has also been shown that naloxone, as an opioidergic antagonist, can reduce or increase the PTSD symptoms and its associated pain.Conclusion Data suggest different roles of opioidergic system and their antagonist in pain control and mood in PTSD. However, further investigations need to be done in order to reveal the role of endogenous opioidergic system and opioidergic antagonist system as a mediator in PTSD patients suffering from acute or chronic pain.
In the present study, the health-protective and therapeutic properties of MET are revisited, giving focusing on the effect of MET on the Nrf2 expression in patients with different pathological conditions. Metformin (MET) regulates high blood glucose, thus being an integral part of the antidiabetic medications used to treat type 2 diabetes mellitus. It belongs to biguanide class medications that are administered through the oral route. Moreover, the agent is widely known for its anticancer, antioxidant, anti-inflammatory, and neuroprotective effects. The MET actually modulates the nuclear factor erythroid-2 related factor-2 (Nrf2) signaling pathway, which in turn yields the above-mentioned medical benefits to patients. The Nrf2 signaling pathways are modulated in multiple ways described subsequently: 1) MET acts on the cancer cells and inactivates Raf-ERK signaling, thus reducing Nrf2 expression, 2) MET obstructs the expression of proteins that are involved in apoptosis of tumor cells and also prevents tumor cells from oxidation through an AMPK-independent pathway; 3) MET carries out Keap1-independent mechanism for reducing the levels of Nrf2 protein in cancer cells; 4) MET upregulates the Nrf2-mediated transcription to stimulate the antioxidant process that prevents oxidative stress in cells system and consequently gives neuroprotection from rotenone and 5) MET downregulates p65 and upregulates Nrf2 which helps improve the angiogenesis impairment stimulated by gestational diabetes mellitus. This article presents an analysis of the health-protective properties of MET and also sheds light on the effect of MET on the Nrf2 expression in patients with different pathological conditions.
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