Selenium alleviates modafinil-induced neurobehavioral toxicity in rat via PI3K/Akt/mTOR/GSK3B signaling pathway and suppression of oxidative stress and apoptosis: in vivo and in silico study.

Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study aims to determine the probable MOD brain toxicity and elucidate the possible role of selenium (Se) in ameliorating the neurotoxicity in rat models. Fifty-four male Albino rats were randomly assigned into nine groups. The groups were G1 (control negative), G2 (Se0.1), G3 (Se0.2), G4 (MOD300), G5 (MOD600), G6 (Se0.1 + MOD300), G7 (Se0.2 + MOD300), G8 (Se0.1 + MOD600), and G9 (Se0.2 + MOD600). After finishing the experiment, blood and brain tissue were harvested for biochemical and histological investigation. Neurobehavior parameters were assessed. Tissue neurotransmitter levels and oxidative stress markers were assessed. Gene expression of PI3K/Akt/mTOR-GSK3B, orexin, and orexin receptor2 was measured by qRT-PCR. Histological and immunohistochemistry assessments, as well as molecular docking, were carried out. MOD-induced neurobehavioral toxicity exhibited by behavioral and cognitive function impairments, which are associated with decreased antioxidant activities, increased MDA levels, and decreases in neurotransmitter levels. Brain levels of mRNA expression of PI3K, Akt, and mTOR were decreased, while GS3K, orexin, and orexin receptors were significantly elevated. These disturbances were confirmed by histopathological brain changes with increased silver and Bax immunostaining and decreased crystal violet levels. MOD induced neurotoxic effects in a dose-dependent manner. Compared with the MOD groups, SE coadministration significantly attenuates MOD-induced toxic changes. Docking study shows the protective role of Se as an apoptosis inhibitor and inflammation inhibitor. In conclusion, Se could be used as a biologically effective antioxidant compound to protect from MOD neurobehavioral toxicity in Wistar rats by reversing behavioral alterations, inflammation, apoptosis, and oxidative injury.

Urine-Derived Stem Cells Versus Their Lysate in Ameliorating Erectile Dysfunction in a Rat Model of Type 2 Diabetes.

Background: Diabetic erectile dysfunction (DED) is a significant consequence of diabetes mellitus, and it is a multifactorial phenomenon that has no definitive treatment until now. Many therapeutic options provide symptomatic improvement rather than addressing the underlying etiology or restoring normal function. Stem cell (SC) therapy represents a potential hope in DED management. It is well established that the regenerative effect of stem cells can be attained by their paracrine action and their ability to differentiate into many cell lineages, including endothelial and smooth muscle cells. Hence, we tried to compare the effects of transplantation of urine-derived stem cells (USCs) or their lysate (USC-L) into the corpora cavernosa (CCs) of rats with DED. Materials and Methods: A total of 55 adult male Wistar rats were included in this study. USCs were obtained from ten healthy rats. Another ten rats did not subject to any intervention and served as a control (group I). Type 2 DM and DED were induced in the remaining 35 rats, but DED was tested and proved in only 24 rats, which were randomly divided into three groups (n = 8 in each). The DED group (group II) and either USCs (2 × 106 cells) or their lysate (200 µl) were transplanted into the CCs of each rat in the other two groups (groups III and IV), respectively. Results: Although the DED rats exhibited deterioration in all copulatory functions as compared to the control group, our histopathological, immunohistochemical, and morphometric results revealed that both USCs and USC-L have significantly restored the cavernous spaces, the ultrastructures of the endothelium that line the cavernous spaces, collagen/smooth muscle ratio, and the mean area percentage of α-SMA in the CCs as compared to DED rats. A respectable number of USCs was detected in the CCs of group III at the 4th week after transplantation, but this number significantly declined by the 8th week. Conclusion: Both USCs and USC-L can repair the structure and ultrastructure of CCs and improve the copulatory functions in the DED rat model. However, USC-L could be better used in DED to guard against the strange behavior of USCs after transplantation and their decreased survivability with time.