Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities

Abstract

Purpose Depression is a mood disorder accompanied by intensive molecular and neurochemical alterations. Currently, available antidepressant therapies are not fully effective and are often accompanied by several adverse impacts. Accordingly, the ultimate goal of this investigation was to clarify the possible antidepressant effects of prodigiosins (PDGs) loaded with selenium nanoparticles (PDGs-SeNPs) in chronic unpredictable mild stress (CUMS)-induced depression-like behavior in rats. Methods Sixty Sprague Dawley rats were randomly allocated into six groups: control, CUMS group (depression model), fluoxetine (Flu, 10 mg/kg)+CUMS, PDGs+CUMS (300 mg/kg), sodium selenite (Na 2 SeO 3 , 400 mg/kg)+CUMS, and PDGs-SeNPs+CUMS (200 mg/kg). All treatments were applied orally for 28 consecutive days. Results PDGs-SeNPs administration prevented oxidative insults in hippocampal tissue, as demonstrated by decreased oxidant levels (nitric oxide and malondialdehyde) and elevated innate antioxidants (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase), in addition to the upregulated expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in rats exposed to CUMS. Additionally, PDGs-SeNPs administration suppressed neuroinflammation in hippocampal tissue, as determined by the decreased production of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β, and interleukin-6), increased anti-inflammatory cytokine interleukin-10, and decreased inflammatory mediators (prostaglandin E2, cyclooxygenase-2, and nuclear factor kappa B). Moreover, PDGs-SeNPs administration in stressed rats inhibited neuronal loss and the development of hippocampal apoptosis through enhanced levels of B cell lymphoma 2 and decreased levels of caspase 3 and Bcl-2-associated X protein. Interestingly, PDGs-SeNPs administration improved hormonal levels typically disrupted by CUMS exposure and significantly modulated hippocampal levels of monoamines, brain-derived neurotrophic factor, monoamine oxidase, and acetylcholinesterase activities, in addition to upregulating the immunoreactivity of glial fibrillary acidic protein in CUMS model rats. Conclusion PDGs-SeNPs may serve as a prospective antidepressant candidate due to their potent antioxidant, anti-inflammatory, and neuroprotective potential.

Selenium Nanoparticles with Prodigiosin Rescue Hippocampal Damage Associated with Epileptic Seizures Induced by Pentylenetetrazole in Rats

“…Accumulating evidence has strongly suggested that changes in monoaminergic, amino acidergic, and cholinergic transmission play crucial roles in regulating epileptogenesis [17,20]. In line with previous reports, the current study identified marked decreases in the levels of 5-HT and its metabolite (5-HIAA), DA, and NE and reduced AChE activity in PTZ-injected rats, which was accompanied by apparent increases in the DOPAC and HVA levels.…”

“…The developed powder was used in the current investigation. Our recent report showed that the obtained nanoformulation (SeNPs-PDG) are characterized with 109.3 average diameters and −13.9 mV as a mean zeta potential record [17]. In addition, TEM analysis revealed that the size of the developed nanoformulation is smaller than 200 nm (Figure S1).…”

Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression

“…Ice water swimming: a container with a depth higher than the rat’s body length, and 4 °C ice water was filled in the container up to the height of the rat’s neck (Albrakati et al. 2021 ). Rats in the normal control group had free access to food and water and were not subjected to any stress.…”

Rutin modified selenium nanoparticles reduces cell oxidative damage induced by H2O2by activating Nrf2/HO-1 signaling pathway

“…33 In recent years, the role of Se NPs in neurodegenerative diseases has been extensively studied and confirmed. 34,35 Therefore, in this context, we processed rutin into selenium-rutin nanoparticles (Se-Rutin) to solve the problem of low bioavailability of rutin and further enhance the anti-oxidation effects. The results demonstrate that Se-rutin significantly alleviates the oxidative stress-induced cell damage and apoptosis by activating Nrf2/HO-1 signal pathway in rat pheochromocytoma (PC12) cells.…”