Sleep deprivation (SD) has been revealed to provoke anxiety-like behavior. Phytochemicals and nanotechnology-based interventions have emerged as promising alternatives due to their pleiotropic activity and enhanced bioavailability. Here we investigated the effect of sodium selenite, Epigallocatechin-3-gallate (EGCG), and EGCG–Selenium nanoparticles (SeNPs) on SD-provoked cortical impairment and tried to recognize the possible underlying mechanisms in addition to in silico analysis of EGCG. SD was provoked in rats utilizing a modified multiple platform model. We performed an in silico analysis of EGCG docked on Bcl2 and MMP2. Forty animals were divided into five groups of eight animals each: animals were given saline orally for 8 days (control); animals were given saline orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD); animals were given Na₂SeO₃ orally with 0.5 mg/kg/day for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/Na₂SeO₃); animals were given 100 mg/kg/day EGCG orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/EGCG); animals were given SeNPs biosynthesized using EGCG and 0.5 mg/kg/day orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/EGCG-SeNPs). Behavioral tests were performed, including the sucrose preference test and the open-field test. Neurotransmitters (norepinephrine, serotonin, and dopamine), monoamine oxidase, ACh, GABA, AChE, neurotropic and glial markers (BDNF and GFAP), as well as neuro-inflammatory, oxidative stress, and apoptotic markers were assessed. Interestingly, sodium selenite, EGCG, and EGCG-SeNP employment mitigated cognitive functions and cortical histopathological alterations in SD-subjected rats. These potential impacts elicited by sodium selenite, EGCG, and EGCG-SeNPs may be related to their impact of elucidating corticosterone increase, cortical neurotransmitter decrease, and neurotropic and glial markers alterations, while also inhibiting the inflammatory and apoptotic axis and upregulating Nrf2 antioxidant cascade. These results prove the neuroprotective potential of sodium selenite, EGCG, and EGCG-SeNPs, especially EGCG-SeNPs in sleep deprivation-subjected rats by ameliorating cortical neuroinflammation, prooxidant alterations, and apoptotic events likely caused by modulating the NOS-2/Nrf2 axis.

Acute kidney injury (AKI) is defined as a quick and often reversible decline in renal performance, as shown by elevated creatinine or reduced urine volume. AKI is a common illness, particularly among hospitalized cases, and can be observed in up to 7% of hospital admissions and 30% of ICU admissions. This study was designed to explore the nephroprotective potential of eco-synthesized quercetin–selenium nanoparticles (QUR-SeNPs) against experimentally glycerol-induced rhabdomyolysis leading to AKI. Forty healthy adult male albino rats were employed in the experiment. Animals were randomly distributed equally into five groups: Control: orally administered with normal saline solution. GLY: orally administered with normal saline (0.9% NaCl) for 15 consecutive days, at day 14, animals of this group received a single dose of intramuscular (im.) injection of 50% glycerol (GLY) (10 mg/kg/day). GLY and quercetin (GLY&QUR): orally administered with quercetin daily for 15 days (50 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). GLY&Na₂SeO₃: orally administered with sodium selenite daily for 15 days (0.5 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). GLY&QUR-SeNPs: orally administered with selenium nanoparticles synthesized using quercetin daily for 15 days (0.5 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). Oxidative stress, inflammatory, and apoptotic markers, in addition to histopathological, gene expression, and immunohistochemical analysis, were assessed for all groups. The results demonstrated that QUR-SeNPs effectively ameliorated renal functional, biochemical, and molecular disturbances through their synergistic antioxidant, anti-inflammatory, and anti-apoptotic potential, surpassing the effects of either quercetin or selenium alone. Biosynthesized selenium nanoparticles using QUR-SeNPs demonstrated remarkable nephroprotective activity by normalizing renal biomarkers, restoring antioxidant capacity, inhibiting inflammatory cytokines, and preventing apoptotic damage. The nanoparticle formulation exhibited superior efficacy to either QUR or Se alone, highlighting the synergistic interplay between selenium and quercetin through enhanced bioavailability, redox stability, and molecular targeting.

Hyperthyroidism frequently impairs liver function through oxidative stress, inflammation, and apoptosis. Effective hepatoprotective therapies remain limited, targeting the effects of natural agents such as Diceratella Elliptica. The current study assessed the hepatoprotective efficacy of Diceratella Elliptica (DE) in an experimental model of L-thyroxin-induced hyperthyroidism. This study performed on 40 male albino rats randomly allocated equally into five groups, control group (HT), L-thyroxin alone (orally, 600 mg/kg daily for 12 days) or in combination with propyl Thiourcil (PU) (intraperitoneally, 10 mg/kg daily for 15 days), and Diceratella Elliptica extract in 200 mg/kg and 400 mg/kg (orally, with a daily dose for 15 days). Hepatic function (ALT, AST, total protein), oxidative stress markers (SIRT1, Nrf2, MDA, NO, GSH, SOD and CAT), inflammatory markers (HMGB1, TLR4, NFκ-B, IL-6 and TNF-α), and apoptotic marker (Caspase-3) were measured, alongside histopathological evaluation. Hyperthyroid rats exhibited marked hepatic injury, with significant elevations in ALT (+85 %), AST (+72 %), MDA (+90 %), NO (+65 %), TNF-α (+70 %), IL-6 (+68 %), and Caspase-3 (+60 %) (P < 0.05), accompanied by substantial reductions in SIRT1 (-45 %), Nrf2 (-40 %), GSH (-50 %), SOD (-42 %), and CAT (-38 %) compared to control. Treatment with D. Elliptica (especially 400 mg/kg) significantly restored liver function, normalizing ALT and AST by nearly 50 %, enhancing antioxidant enzyme activities by 35-55 %, and down-regulating inflammatory and apoptotic markers (p < 0.05). Histological examination revealed restoration of hepatic cords, reduced inflammatory infiltration, and preserved hepatocyte morphology. Diceratella Elliptica exerts potent hepatoprotective activity against hyperthyroidism-induced hepatic injury. Its concurrent activation of SIRT1 and Nrf2, along with suppression of NF-κB-mediated inflammation and Caspase-3-dependent apoptosis, suggests modulation of the oxidative stress-inflammation-apoptosis axis. These findings support Diceratella Elliptica as a promising natural therapeutic candidate for thyroid-related liver dysfunction.

5-Fluorouracil (5-FU) is a cornerstone chemotherapeutic agent that is extensively utilized in the management of malignancies; however, its clinical utility is constrained by its narrow therapeutic index and dose-limiting toxicities. The study aimed to study the hepato-nephroprotective effects of epigallocatechin gallate (EGCG) and EGCG mediated selenium nanoparticles and their effect in mitigating the toxicity induced by 5-FU. EGCG-functionalized selenium nanoparticles (EGCG-SeNPs) were produced by mixing sodium selenite, with EGCG acting as both the reducing and stabilizing agent. Nanoparticles were characterized using UV-vis spectroscopy, FT-IR, dynamic light scattering, zeta potential analysis, and transmission electron microscopy. 35 adult rats were randomly assigned to control, 5-FU, 5-FU + Na₂SeO₃, 5-FU + EGCG, and 5-FU + EGCG-SeNPs groups. Hepatorenal toxicity was induced by intraperitoneal 5-FU administration during the final five days of the experiment. Serum biochemical markers, tissue oxidative stress, antioxidant enzyme, inflammatory cytokine levels, and apoptosis-related gene expression were evaluated. Immunohistochemical analysis of Nrf2 and Keap1 and histopathological examination of tissues were performed. 5-FU induced severe hepatorenal toxicity, evidenced by marked elevations in liver and kidney function biomarkers, excessive oxidative stress, inflammatory cytokine overproduction, NF-κB activation, and apoptotic signaling. Treatment with EGCG-SeNPs markedly ameliorated 5-FU-induced hepatic and renal dysfunction, restoring liver enzyme and kidney biomarker levels to near-normal levels more effectively than EGCG or sodium selenite alone. EGCG-SeNPs significantly suppressed lipid peroxidation, NGAL, and inflammatory mediators while robustly enhancing antioxidant defenses and activating the Nrf2/HO-1 pathway with concomitant Keap-1 downregulation, strongly inhibited NF-κB signaling, normalized cytokine balance, reduced poly (ADP-ribose) (PAR) activation, and attenuated apoptosis. EGCG–SeNPs confer superior protection against 5-FU–induced hepatorenal toxicity compared to EGCG or inorganic selenium alone. The potent protective effects of EGCG–SeNPs are mediated through coordinated antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, primarily via activation of the Nrf2/HO-1 axis and suppression of NF-κB signaling.