Can tailored nanoceria act as a prebiotic? Report on improved lipid profile and gut microbiota in obese mice.

BACKGROUND: Microbiome modulation is a pillar intervention to treat metabolic syndrome, prestages, and cascade of related pathologies such as atherosclerosis, among others. Lactobacillus and Bifidobacterium probiotic strains demonstrate efficacy to reduce obesity, dyslipidemia, and improve metabolic health. Novel prebiotic substances composed with known probiotics may strongly synergize health benefits to the host. The aim of this study was to evaluate beneficial effects of Lactobacillus and Bifidobacterium strains (probiotics) if composed with nanoceria (potential prebiotic) to reduce cholesterol levels and restore gut microbiota in obese mice. MATERIALS AND METHODS: Two lines of mice were used in the study: BALB/c mice (6-8 weeks, 18-24 g) and CBA mice (11-12 months, 20-26 g); experimental animals were fed by fat-enriched diet 3 weeks before the evaluation. Animals were divided into groups to test probiotic strains and nanoceria. All groups received probiotic strains orally and cerium dioxide orally or intravenously in various composition. A group of untreated animals was used as a control. Cholesterol level and gut microbiota of mice were studied. RESULTS: Cerium dioxide nanoparticles, probiotic strain L. casei ІМV В-7280, and composition B. animalis VKB/B. animalis VKL applied separately and in different combinations all reduced at different levels free and bound cholesterol in blood serum of mice fed by fat-enriched diet. The combination of 0.01 M nanoceria and probiotic strain L. casei ІМV В-7280 resulted in the fastest cholesterol level decrease in both young and mature animals. Oral administration of CeO2 applied alone reduced the number of microscopic fungi in the gut of mice and Gram-positive cocci (staphylococci and/or streptococci). Application of L. casei IMV B-7280 as a probiotic strain increased most significantly the number of lactobacilli and bifidobacteria in the gut of mice. The most significant normalization of gut microbiota was observed after oral administration of alternatively either L. casei IMV B-7280 + 0.1 M CeO2 or L. casei IMV B-7280 + 0.01 M CeO2. CONCLUSION: Dietary application of nanoceria combined with probiotic strains L. casei IMV B-7280, B. animalis VKB, and B. animals VKL has significantly reduced both free and bound cholesterol levels in serum. Simultaneous administration of probiotics and cerium nanoparticles as a prebiotic, in various combinations, significantly enhanced positive individual effects of them on the gut microbiota spectrum. The presented results provide novel insights into mechanisms behind nutritional supplements and open new perspectives for application of probiotics combined with substances demonstrating prebiotic qualities benefiting, therefore, the host health. Follow-up translational measures are discussed to bring new knowledge from lab to the patient. If validated in a large-scale clinical study, this approach might be instrumental for primary and secondary prevention in obese individual and patients diagnosed with diabetes. To this end, individualized prediction and treatments tailored to the person are strongly recommended to benefit the health condition of affected individuals.

Efficacy of nanoceria for periodontal tissues alteration in glutamate-induced obese rats-multidisciplinary considerations for personalized dentistry and prevention.

BACKGROUND: Nowadays, we face the global epidemic of obesity, that is known to contribute to the development of many diseases, such as the oral cavity pathologies. Dental and oral pathologies are frequently caused by and overlapped with systemic multifactorial diseases such as obesity being its early indicators and risk factors. The aim was to study the influence of nanoceria on periodontal tissues alteration in glutamate (MSG)-induced obese rats. METHODS: We included 52 Wistar rats of both genders and divided into four groups: newborn rats in group 1 (control) received subcutaneously 8 µl/g saline. Group 2 received 3 to 4 mg/g MSG subcutaneously on the second, fourth, sixth, eighth, and tenth day of life; group 3-intragastric administration of nanocrystalline cerium dioxide at a dose of 1 mg/kg volume of 2.9 ml/kg against the background of glutamate-induced obesity; the fourth group of animals was treated with a solution of sodium citrate intragastric volume of 2.9 ml/kg (solvent of nanocrystalline cerium). We determined the total proteolytic activity, the total antitrypsin activity, the content-free fucose and glycosaminoglycanes (GAG), content of TBA-active of products, the content of oxidation-modified proteins (OMB), and catalase activity in the homogenate of soft periodontal tissues of rats. RESULTS: Intragastric injection of nanoceria prevents activation of proteolytic processes, reducing the catabolism of glycoproteins and proteoglycans of periodontal tissue in MSG-induced obese rats. Injection of nanoceria prevents activation of proteolytic processes, significantly decreases the total proteolytic activity, and inhibits the activation of free radical oxidation in periodontal tissues of rats compared with MSG-induced obesity model without corrections. Further, it significantly increases the total antitrypsin activity in periodontal tissues by 1.7 times, TBA-reagents by 1.7 times, and content of OMB by 1.4 times compared with glutamate-induced obese animals. CONCLUSIONS: MSG-induced obesity triggers periodontal tissue alterations in the rat model. Nanoceria contributes to the corrections of pathological changes in periodontal tissues in glutamate-induced obese rats via balancing protein-inhibitory capacity and reducing the depolymerization of fucosylated proteins and proteoglycans and antioxidative activity.

Energy Transfer in Ce0.85Tb0.15F3 Nanoparticles-CTAB Shell-Chlorin e6 System.

Formation and electronic excitation energy transfer process in the nanosystem consisting of Ce0.85Tb0.15F3 nanoparticles, cetrimonium bromide (CTAB) surfactant, and chlorin e6 photosensitizer were studied. It was shown that chlorin e6 molecules bind to Ce0.85Tb0.15F3 NP in the presence of CTAB forming thus Ce0.85Tb0.15F3 NP-CTAB-chlorin e6 nanosystem. We consider that binding occurs via chlorin e6 embedding in the shell of CTAB molecules, formed around NP. In the Ce0.85Tb0.15F3 NP-CTAB-chlorin e6 nanosystem, electronic excitation energy transfer from Ce3+ to chlorin e6 takes place both directly (with the 0.33 efficiency for 2 µM chlorin e6) and via Tb3+.

Cerium dioxide nanoparticles possess anti-inflammatory properties in the conditions of the obesity-associated NAFLD in rats.

BACKGROUND: Obesity is a risk factor for non-alcoholic fatty liver disease (NAFLD). The disease is associated with impairment of pro/antioxidant equilibrium and the inflammation in liver tissue. The aim of the work was to investigate the anti-inflammatory properties of the nanocrystalline cerium dioxide (nCeO2) on the rat model of NAFLD associated with monosodium glutamate (MSG)-induced obesity. METHODS: The study was carried out on three groups of rats: control, MSG- and MSG+nCeO2. They were injected with saline (control) or MSG. A month after born MSG-rats had been treated with water in a volume of 2.9ml/kg, MSG+CeO2 groups - with CeO2 intragastrically (i.g.). The anthropometric and carbohydrate metabolism parameters, content of proinflammatory cytokines (interleukin (IL)-1ß, IL-12Bp40, interferon-γ (INF-γ)) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor-ß (TGF-ß)) were measured by ELISA. RESULTS: We have demonstrated the anti-obesity effect of nanocrystalline cerium dioxide and for the first time its anti-inflammatory properties. Nanoparticles reduced the content of pro-inflammatory cytokines (IL-1ß, IL-12Bp40) in rat serum and restored the level of anti-inflammatory cytokines (IL-4, IL-10, TGF-ß) to the control values. CONCLUSION: The precise mechanisms of this phenomenon remain to be unclear but we suppose they are at least partially associated with the strong anti-oxidant action of studied substance. Nanocrystalline cerium dioxide attenuates the inflammatory processes in rat blood that can prevent obesity complications and liver injury.

Antioxidative effects of cerium dioxide nanoparticles ameliorate age-related male infertility: optimistic results in rats and the review of clinical clues for integrative concept of men health and fertility.

BACKGROUND: Male infertility has largely idiopathic, multifactorial origin. Oxidative stress is a major factor that affects spermatogenesis, in particular in aging. Cerium dioxide nanoparticles (CNPs) due to their antioxidative properties are promising to impact on the development of male infertility. The aims of this study were to investigate the effects of CNPs on fertility parameters in 24-month male rats and to overview relevant literature in the field of personalized treatments, predictive diagnosis, and preventive measures for male health and fertility. METHODS: We included 30 24-month-old male rats. After a week of adaptation to the standard diet, the rats were randomly divided into three groups with ten rats in each. Group 1 (controls) received only a standard diet. The rats of group 2 and 3 in adjunct to the standard diet during 10 days received intragastrically 10 % sodium citrate and citrate-coated CNPs in dose 1 mg/kg, respectively. We assessed sex hormones, epididymal sperm parameters and spermatogenesis, ultrasound, and morphological data of rat reproductive organs. RESULTS: After a 10-day administration of CNPs, we revealed significant decrease of lipid peroxidation product levels in serum and increase of catalase and SOD activity, associated with increase of sperm count (p < 0.001) and improvement in quantitative sperm parameters (motility, viability, and percentage of spermatozoa). We found no significant changes between sperm quantitative parameters in citrate-treated rats and controls and observed age-related decrease of activated Leydig cell number and focal atrophy of the seminiferous tubules. In CNP group, we observed regeneration of seminiferous tubules, increase number and activation of Leydig cells, and 2.5-fold significant increase of serum testosterone. Ultrasound data showed the slight increase of linear measurement and volume of rat testes in CNP group. Review highlights the benefits for predictive diagnosis, preventive measures, and personalized approaches to manage male infertility in the general concept of male health also related to aging. CONCLUSION: Citrate-coated 2-5-nm CNPs lead to increase in sex hormones levels, sperm count, and quality, as well as the activation of spermatogenesis in 24-month-old male rats. Nanoceria demonstrated the perspectives to be an effective infertility treatment via reduction of oxidative stress in male reproductive organs, in particular in aging.

Nanocrystalline cerium dioxide efficacy for gastrointestinal motility: potential for prokinetic treatment and prevention in elderly.

BACKGROUND: Constipation is a common condition, with prevalence after 65 years, is a major colorectal cancer risk factor. Recent works have demonstrated advances in personalized, preventive nanomedicine, leading to the construction of new materials and nanodrugs, in particular, nanocrystalline cerium dioxide (NCD), having strong antioxidative prebiotic effect. The aim of our study was to investigate the influence of NCD on motor function of the stomach and colon in vivo and contractive activity of smooth muscles in different year-old rats. METHODS: We included 80 rats: 3- (weight 130-160 g, n = 40) and 24-month old (weight 390-450 g, n = 40), divided into four groups as follows: І-control group; rats of II-ІV groups were injected intragastrically one injection per day during 10 days, 3 ml of water 3 ml/kg stabilizing solution, аnd 1 mmol/ml NCD, respectively. In all animals, we recorded spontaneous and carbachol-stimulated (0.01 mg/kg) gastrointestinal tract motor activity. We used the index of motor activity (IMA), expressed in cmH2O, for characterization of the motor function. We investigated smooth muscle contraction by tenzometric method, studied the spontaneous and stimulated motility by ballonographic method. RESULTS: IMA reduced by 21.1 + 0.2% (p < 0.01) in the old rats of the control group compared with the young rats. A 10-day administration of NCD increased IMA in the stomach of young rats by 9.3% (р < 0.001) vs the control group. The exposure of NCD increased the amplitude of contraction to 34.2 ± 5.4 mN (n = 10) in the stomach of old rats and increased by 32.1 ± 2.4% vs the control group (p < 0.05). NCD did not influence acetylcholine (ACh) contractions in the stomach of young rats; however, in the stomach of old rats, V nr increased by 90 ± 15.2% (р < 0.001). CONCLUSIONS: The index of motor activity is decreased in old rats. Nanocrystalline cerium dioxide increased the index of motor activity in all groups of rats and also evoked a significant increase of colon contractions in old rats.