ABSTRACT
Introduction: The ratio of Ce3+/Ce4+ in their structure confers unique functions on cerium oxide nanoparticles (CeO2NPs) containing rare earth elements in scavenging free radicals and protecting against oxidative damage. The potential of CeO2NPs to protect testosterone synthesis in primary mouse Leydig cells during exposure to 1,800 MHz radiofrequency (RF) radiation was examined in vitro. Methods: Leydig cells were treated with different concentrations of CeO2NPs to identify the optimum concentration for cell proliferation. The cells were pretreated with the optimum dose of CeO2NPs for 24 hrs and then exposed to 1,800 MHz RF at a power density of 200.27 µW/cm2 (specific absorption rate (SAR), 0.116 W/kg) for 1 hr, 2 hrs, or 4 hrs. The medium was used to measure the testosterone concentration. The cells were collected to determine the antioxidant indices (catalase [CAT], malondialdehyde [MDA], and total antioxidant capacity [T-AOC]), and the mRNA expression of the testosterone synthase genes (Star, Cyp11a1, and Hsd-3ß) and clock genes (Clock, Bmal1, and Rorα). Results: Our preliminary result showed that 128 µg/mL CeO2NPs was the optimum dose for cell proliferation. Cells exposed to RF alone showed reduced levels of testosterone, T-AOC, and CAT activities, increased MDA content, and the downregulated genes expression of Star, Cyp11a1, Hsd-3ß, Clock, Bmal1, and Rorα. Pretreatment of the cells with 128 µg/mL CeO2NPs for 24 hrs followed by RF exposure significantly increased testosterone synthesis, upregulated the expression of the testosterone synthase and clock genes, and increased the resistance to oxidative damage in Leydig cells compared with those in cells exposed to RF alone. Conclusion: Exposure to 1,800 MHz RF had adverse effects on testosterone synthesis, antioxidant levels, and clock gene expression in primary Leydig cells. Pretreatment with CeO2NPs prevented the adverse effects on testosterone synthesis induced by RF exposure by regulating their antioxidant capacity and clock gene expression in vitro. Further studies of the mechanism underlying the protective function of CeO2NPs against RF in the male reproductive system are required.
Subject(s)
Antioxidants/pharmacology , Cerium/pharmacology , Leydig Cells/drug effects , Radio Waves/adverse effects , Testosterone/biosynthesis , Animals , Antioxidants/metabolism , Catalase/metabolism , Cell Proliferation/drug effects , Cerium/chemistry , Circadian Rhythm Signaling Peptides and Proteins/genetics , Gene Expression Regulation/drug effects , Leydig Cells/physiology , Male , Malondialdehyde/metabolism , Mice, Inbred C57BL , Nanoparticles/chemistryABSTRACT
OBJECTIVE: To study the effects of cerium oxide nanoparticles( CeO_2 NPs)on cognitive function in 48 hours of sleep deprived male mice and explore its mechanism. METHODS: Thirty-six healthy clean ICR male mice( four weeks old) were randomly divided into 6 groups: blank control group, solvent control group, sleep deprivation control group, low, medium and high dose groups of CeO_2 NPs. 1 m L of distilled water were given to mice of blank group, 1 m L of solvent were given to mice of solvent control and sleep deprivation control group, 1 mL of CeO_2 NPs solvent( 4, 8, 16 mg/kg) were administered to mice of low, medium and high dose groups of CeO_2 NPs. Each group of mice received intragastric administration for 30 days. On the 31 st day, a single platform water environment method was used for 48 hours of sleep deprivation on mice. Then, the cognitive ability of the mice was tested by Y-maze. Further, the antioxidant( CAT, MDA, T-AOC) and neurotransmitters( NO, Glu) in mice brain tissue were measured also. RESULTS: Compare with the solvent control group, 48 hours of sleep deprivation reduced the cognitive ability of mice [( 36 ± 2) times vs. ( 20 ± 2) times, P = 0. 0006; 10. 753%± 0. 031% vs. 24. 927% ± 0. 972%, P = 0. 00000045 ], CAT activity [( 78. 151 ±17. 683) nmol/mg prot vs. ( 198. 155 ± 14. 437) nmol/mg prot, P = 0. 0008]and the level of T-AOC [( 103. 630 ± 24. 209) U/mg prot vs. ( 264. 599 ± 50. 223) U/mg prot, P =0. 007], but improved the content of MDA [( 9. 499 ± 1. 249) nmol/mg prot vs. ( 6. 157± 0. 373) nmol/mg prot, P = 0. 0113 ], NO [( 11. 608 ± 1. 281) µmol/mg prot vs. ( 3. 628 ± 1. 064) µmol/mg prot, P = 0. 001]and Glu[( 4. 731 ± 0. 131) µg/mg prot vs. ( 4. 476 ± 0. 126) µg/mg prot, P = 0. 03] in the brain. Low, medium and high dose Ce O2 NPs enhanced cognitive performance of the sleep deprived mice. Among three dose groups, the medium dose groups most significantly improved the cognitive ability of mice[( 27 ± 2) times vs. ( 36 ± 2) times, P = 0. 005; 18. 743% ± 0. 245% vs. 10. 753% ±0. 031%, P = 0. 0000006 ], increased CAT activities [( 238. 065 ± 19. 393) nmol/mg prot vs. ( 78. 151 ± 17. 683) nmol/mg prot, P = 0. 00045] and T-AOC levels [( 210. 516± 11. 339) U/mg prot vs. ( 103. 630 ± 24. 209) U/mg prot, P = 0. 002], decreased MDA[( 6. 528 ± 1. 162) nmol/mg prot vs. ( 9. 499 ± 1. 249) nmol/mg prot, P = 0. 039], NO[( 5. 651 ± 0. 239) µmol/mg prot vs. ( 11. 608 ± 1. 281) µmol/mg prot, P = 0. 001]and Glu levels [( 4. 358 ± 0. 016) µg/mg prot vs. ( 4. 731 ± 0. 131) µg/mg prot, P = 0. 008]. CONCLUSION: Ce O2 NPs can improve the cognitive ability of sleep deprived male mice, improve the antioxidant capacity of brain, reduce free radical damage to the nerves of brain, and regulate the neurotransmitters of brain.
