Antioxidants · 6 authors, 2 centres
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This study synthesized GLSO-functionalized selenium nanoparticles (GLSO@SeNPs) that protect pancreatic beta cells from palmitic acid-induced apoptosis. The nanoparticles reduced oxidative stress by restoring antioxidant enzyme activity and modulating the MAPK signaling pathway. These findings suggest GLSO@SeNPs as a potential therapeutic approach for type 2 diabetes by preserving beta cell function.
**Background:** Oxidative stress damage of pancreatic beta cells is a key mechanism in type 2 diabetes pathogenesis. Long-term elevation of free fatty acids, particularly palmitic acid (PA), induces reactive oxygen species (ROS) accumulation in beta cells, leading to apoptosis and dysfunction. Ganoderma lucidum spore oil (GLSO) has strong antioxidant activity but poor solubility and stability. Selenium nanoparticles (SeNPs) also exhibit antioxidant properties. This study aimed to synthesize GLSO-functionalized selenium nanoparticles (GLSO@SeNPs) and evaluate their protective effects against PA-induced lipotoxicity in INS-1E rat insulinoma beta cells.
**Methods:** GLSO@SeNPs were synthesized using a high-pressure homogeneous emulsification method combining GLSO nanoemulsions (GLSO@NEs) and SeNPs (prepared via ascorbic acid reduction of sodium selenite with lentinan stabilization) in a Poloxam 407 hydrogel. Nanoparticles were characterized by TEM, dynamic light scattering, and Raman spectroscopy. Stability was assessed in water, PBS, and cell culture medium over 168 hours. Hemocompatibility was tested using human erythrocytes. INS-1E cells were pretreated with GLSO@NEs, SeNPs, or GLSO@SeNPs for 6 hours, then exposed to 0.3 mM PA for 24 hours. Assays included: CCK-8 for viability, flow cytometry for cell cycle and mitochondrial membrane potential (JC-1 staining), DCFH-DA for ROS, commercial kits for SOD, MDA, GSH, CAT, TrxR, and GPx activity, HPLC-ICP-MS for selenium metabolism, and western blot for MAPK pathway and apoptosis-related proteins.
**Key Results:** GLSO@SeNPs had a particle size of approximately 220 nm and negative zeta potential, with stable size in water and PBS over 168 hours and hemolysis rate below 0.1%. PA (0.3 mM) reduced INS-1E cell viability to approximately 60%. GLSO@SeNPs (0.04 μL/mL) significantly increased viability compared to PA alone. PA induced G2/M phase arrest (35.28% of cells), which was reduced to 16.79% by GLSO@SeNPs. SubG1 content (apoptosis indicator) increased to nearly 30% with PA and was reduced to 5.22% by GLSO@SeNPs. PA caused mitochondrial membrane potential loss (30.85% monomeric JC-1 vs. 7.73% with GLSO@SeNPs) and mitochondrial fragmentation. PA increased intracellular ROS to approximately 130% of control; GLSO@SeNPs reduced this to approximately 110%. PA significantly decreased activities of SOD, GSH, GPx, TrxR, and CAT, and increased MDA; GLSO@SeNPs restored these to near-control levels. Selenium metabolism analysis showed GLSO@SeNPs were converted to SeCys2 in cells, reaching 0.086 μg/5×10^6 cells after 24 hours. Western blot showed PA increased phosphorylation of p38 and JNK, decreased p-ERK (to 0.15 times control) and p-AKT, and activated caspases 3, 8, and 10 with increased Bax, Bim, Bad and decreased Bcl-2. GLSO@SeNPs reversed all these changes.
**Clinical Implications:** This study provides preclinical evidence that GLSO@SeNPs may protect pancreatic beta cells from lipotoxicity-induced apoptosis through antioxidant and anti-apoptotic mechanisms involving the MAPK pathway. The dual antioxidant activity of GLSO and SeNPs, combined with improved stability from nanoformulation, addresses key limitations of GLSO alone. However, these findings are limited to in vitro experiments using a rat insulinoma cell line. Future animal studies and pharmacokinetic evaluations are needed to validate therapeutic potential for type 2 diabetes.