THE CONTENT OF METALLOPROTEINASE-2 AND METALLOPROTEINASE-9 IN THE SKIN OF RATS OF DIFFERENT AGES AFTER CLOSURE OF THE WOUND BED.

OBJECTIVE: The aim: The aim of the study was to determine the content of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) in the skin of rats of different ages after closure of the wound bed. PATIENTS AND METHODS: Materials and methods: The studies were performed on 40 white nonlinear male rats, 20 of which were 3 months old and 20 - 12 months. In each group 10 rats were control and in 10 others facelift operations were performed and cut wounds on the anterior abdominal wall were simulated. On the day of complete healing, the animals were killed, and the skin was cut in the areas of the former wound bed. In control rats, the skin was excised in the same places. The content of MMPs was determined in the skin by enzyme-linked immunosorbent assay. RESULTS: Results: In rats aged 3 months after re-epithelialization of the wound bed, the content of MMP-2 was 17,1% higher compared to control rats but the level of MMP-9 didn't change. In control rats aged 12 months, the levels of MMP-2 and MMP-9 in the skin were 22,9% and 34,4% lower compared to control rats at 3 months of age. In rats 12 months of age after re-epithelialization of the wound bed, the content of MMP-2 and MMP-9 were 92,6% and 102,5% higher compared to control rats. CONCLUSION: Conclusions: We suggested that the violation of homeostasis between MMPs in rats 12 months of age disrupts wound healing and promotes the formation of pathological scars.

New insights on strain-specific impacts of probiotics on insulin resistance: evidence from animal study.

BACKGROUND AND AIMS: сomparative animal study of effectiveness of intermittent administration of lyophilized single-, three- and alive multistrain probiotic in short courses on insulin resistance (IR) in rats with experimental obesity. METHODS: 70 rats were divided into 7 groups (n = 10 in each). Rats of group I were left intact. Newborn rats in groups II-VII were administered monosodium glutamate (MSG) (4 mg/g) by injection. Rats in group II (MSG-obesity group) were left untreated. The rats in groups III-V received lyophilized mono-probiotics B.animalis VKL, B.animalis VKB, L.casei IMVB-7280 respectively. The rats in group VI received all three of these probiotic strains mixed together. Group VII was treated with multi-probiotic "Symbiter", containing 14 different live probiotic strains (Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter genera). RESULTS: Treatment of newborn rats with MSG lead to the development of obesity in all MSG-obesity rats and up to 20-70% after probiotic administration. Additions to probiotic composition, with preference to alive strains (group VII), led to significantly lower rates of obesity, decrease in HOMA-IR (p < 0.001), proinflammatory cytokines levels - IL-1ß (p = 0.003), IL-12Bp40 (p < 0.001) and elevation of adiponectin (p = 0.003), TGF-ß (p = 0.010) in comparison with MSG-obesity group. Analysis of results in groups treated with single-strain probiotics (groups III-V) shows significant decrease in HOMA-IR, but changes were less pronounced as compared to mixture groups and did not achieve intact rats level. Other metabolic parameters were not affected significantly by single strains. CONCLUSION: Our findings provide major clues for how to design and use probiotics with more efficient compositions in obesity and IR management and may bring new insights into how host-microbe interactions contribute to such protective effects.

Hepatic Encephalopathy Aggravated by Systemic Inflammation.

BACKGROUND: The pathogenesis of hepatic encephalopathy (HE) is only partially understood. Beside ammonia accumulation in brain, a proinflammatory component has been suggested as precipitating event. OBJECTIVES: To evaluate the role of cytokines in cirrhosis for development of HE. METHODS: Pro- and anti-inflammatory cytokine profiles were determined in rats with CCL4-induced cirrhosis and HE as well as in patients with cirrhosis either due to metabolic disorders or chronic hepatitis C virus (HCV) with various grades of concomitant HE and depression. RESULTS: In the rat model and human cirrhosis a proinflammatory cytokine pattern (elevation of interferon gamma, interleukin [IL]-1ß, IL-6) was registered which in humans correlated to the degree of HE and depression. The most prominent elevation of proinflammatory cytokines was observed in chronic HCV as an additional inflammatory stimulus. In all cases of cirrhosis a comparable background activation of anti-inflammatory cytokines (e.g., IL-4) was detected which was interpreted as a physiologic counterbalance mechanism. CONCLUSIONS: The degree of HE and depression correlated with a proinflammatory cytokine pattern. It suggests that beside ammonia elevation, inflammatory cytokines determine occurrence and severity of hepatic encephalopathies. Thus, it can be defined a preferential therapeutic target.

Efficacy of Probiotics and Smectite in Rats with Non-Alcoholic Fatty Liver Disease.

INTRODUCTION AND AIM: Today probiotics have been suggested as a treatment for the prevention of non-alcoholic fatty liver disease (NAFLD). Smectite is a natural silicate that binds to digestive mucous and has the ability to bind endo- and exotoxins. The present study was designed to determine whether probiotics plus smectite is superior to probiotic alone on the monosodium glutamate (MSG) induced NAFLD model in rats. MATERIALS AND METHODS: We included 60 rats divided into 4 groups 15 animals in each. Rats of group I were intact. Newborns rats of groups II-IV were injected with MSG. The III (Symbiter) group received 2.5 ml/kg of multiprobiotic "Symbiter" containing concentrated biomass of 14 probiotic bacteria genera. The IV (Symbiter+Smectite) groups received "Symbiter Forte" combination of probiotic biomass with smectite gel (250 mg). RESULTS: In both interventional groups reduction of total NAS score as compared to MSG-obesity was observed. Indeed similar values of steatosis score (0.93 ± 0.22 vs. 0.87 ± 0.16) in both treatment groups, we observed that lower total score for Symbiter+ Smectite are associated with more pronounced reduction of lobular inflammation (0.13 ± 0.09 vs. 0.33 ± 0.15) as compared to administration of probiotic alone. This data accompanied with significant reduction of IL-1 and restoration of IL-10 between these 2 groups. CONCLUSIONS: Additional to alive probiotic administration of smectite gel due to his absorbent activity and mucus layer stabilization properties can impact on synergistic enhancement of single effect which manifested with reduction of lobular inflammation and at list partly steatohepatitis prevention.

Treatment efficacy of a probiotic preparation for non-alcoholic steatohepatitis: A pilot trial.

OBJECTIVE: To evaluate the therapeutic effect of a probiotic cocktail containing Lactobacilli, Bifidobacteria and Streptococcus thermophilus on non-alcoholic steatohepatitis (NASH). METHODS: In this open-label trial, 75 patients with NASH fed a low-fat/low-calorie diet were randomly divided into the control group and experimental group, with the latter receiving the probiotic cocktail once daily for 12 weeks. RESULTS: All patients were diagnosed with fatty liver by ultrasound examination and had elevated levels of γ-glutamyl transferase (GGT) and alanine aminotransferase (ALT), and slightly increased body mass index (BMI) and cholesterol levels. BMI and serum cholesterol were reduced by the low-fat/low-calorie diet but ALT was not. However, the short-term (12-week) treatment with the probiotic cocktail caused a significant (by >20%) reduction of serum ALT compared with controls, indicating mitigation of inflammation. Accordingly, liver stiffness was decreased in the probiotic-treated group compared with the control group (P < 0.05). Moreover, a more significant decrease in the BMI and serum cholesterol was observed in the probiotic-treated group compared with control (P < 0.05). However, the reduction of GGT as a steatosis marker was insignificant. The composition of stool microbiota in probiotic-treated patients demonstrated a shift towards a normal pattern for all bacterial species examined. No adverse events were observed in any patient during the trial. CONCLUSION: Short-term treatment with the probiotic cocktail caused significant improvement of liver inflammation without adverse events and, thus, may represent a promising candidate therapeutic approach for NASH.

Probiotics for experimental obesity prevention: focus on strain dependence and viability of composition.

INTRODUCTION: a comparative animal study of the efficacy of intermittent short-course administration of lyophilised single-, three-, and live multistrain probiotic on obesity. METHODS: We included 70 rats divided into seven groups (n = 10 in each). Rats of group I were intact. Newborn rats of groups II-VII were injected with monosodium glutamate (MSG) (4 mg/g). Rats of group II (MSG-obesity group) were untreated. The group III-V received lyophilised monoprobiotics B. animalis VKL, B. animalis VKB, and L. casei IMVB-7280, respectively. Group VI received the mix of these three probiotic strains. Group VII was treated with multiprobiotic "Symbiter", which contains 14 live probiotic strains (Lactobacillus, Bifi-dobacterium, Propionibacterium, Acetobacter genera). RESULTS: Neonatal treatment with MSG caused stunted growth, which is why, despite the lack of weight gain dynamics and absence of significant food consumption rate and body weight changes at day 120, we noted the development of obesity in all MSG-obesity rats and in up to 20-70% after probiotic administration. Supplementation of probiotic composition, with preference to live strains, led to a significantly lower prevalence of obesity, and reduction of VAT weight and serum lipid levels as compared to single-strain probiotic. In our comparative single-strain analysis a trend towards more pronounced hypolipidaemic effect and VAT weight reduction was observed for lyophilised L. casei IMVB-7280 as compared to B. animalis VKL and VKB strains. CONCLUSIONS: Multistrain formed mutualistic interactions in mixtures and therefore able to share with different metabolites, affect differ-ent receptors and produced various of biologically active compounds which synergistic overall effect greater than the sum of the single effects.

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.

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.

Effects of polyphenol compounds melanin on NAFLD/NASH prevention.

BACKGROUND: One of the pathogenic mechanisms of the progression non-alcoholic liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is the accumulation of reactive oxygen species (ROS). So, antioxidant therapy is necessary for successful treatment of the liver injury. We have paid attention to melanin produced by yeast Nadsoniella nigra strain X-1 as novel antioxidant and anti-inflammatory agents with low toxicity. In current study we aimed to investigate the preventive effect of melanin on the monosodium glutamate (MSG) induced NAFLD model in rats. METHODS: The study was carried out on 45 Wistar rats that were divided into 3 groups: intact, MSG- and MSG+melanin groups (n=15 in each group). Newborn rats of MSG- and MSG+melanin groups were administered with MSG (4mg/g, 8µl/g, subcutaneously) at 2nd-10th days of life. Since the age of 1 month, rats of MSG-group were treated with water (0.25ml/100g), rats of MSG+melanin groups-with melanin (1mg/kg) dissolved in water (0.25ml/100g). INTRODUCTION: had been performed intermittently (two-week courses alternated with two-week breaks) for 3 months. In 4-month rats anthropometrical parameters and visceral adipose tissue (VAT) mass were estimated. To assess morphological changes in liver we used NAS (NAFLD activity score). The content of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-12Bp40, interferon (INF)-γ) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor (TGF)-ß) were measured by ELISA. RESULTS: We found significantly lower total score (1.0±0.19 vs 3.33±0.36, p<0.001), degree of steatosis (0.73±0.18 vs 1.80±0.17, p<0.001) and manifestation of lobular inflammation (0.27±0.11 vs 1.20±0.17, p<0.001) due to NAFLD activity score in MSG+melanin group compared to MSG-obesity. NASH we confirmed only in 33.3% of rats with MSG-obesity that was significantly higher than after melanin (6.7%) administration (p=0.033). Melanin administration reduce amount of visceral fat on 44.5% (p<0.001) as compared to MSG-obesity group. Melanin reduced the content of IL-1ß in rat serum and restored the level of anti-inflammatory cytokines (IL-10, TGF-ß) to the control values. CONCLUSION: Thus, the administration of melanin can prevent development of NAFLD/NASH in rats with MSG-induced obesity and can be considered as possible novel therapeutic agents but further studies to confirm its action needed.

Probiotics Supplemented with Omega-3 Fatty Acids are More Effective for Hepatic Steatosis Reduction in an Animal Model of Obesity.

Today probiotics have been suggested as a treatment for the prevention of NAFLD. Omega-3 fatty acid supplementation may have beneficial effects in regulating hepatic lipid metabolism, adipose tissue function and inflammation. The present study was designed to determine whether probiotics plus omega-3 are superior to probiotics alone on the monosodium glutamate (MSG)-induced NAFLD model in rats. We included 60 rats divided into four groups, 15 animals in each. Rats of group I were intact. Newborn rats of groups II-IV were injected with MSG. The III (Symbiter) group received 2.5 ml/kg of multiprobiotic "Symbiter" containing concentrated biomass of 14 probiotic bacteria genera. The IV (Symbiter-Omega) groups received "Symbiter-Omega" combination of probiotic biomass supplemented with flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5 %). In both interventional groups reduction in total NAS score was observed. Supplementation of alive probiotic mixture with omega-3 fatty acids lead to 20 % higher decrease in steatosis score (0.73 ± 0.11 vs 0.93 ± 0.22, p = 0.848) and reduction by 16.6 % of triglycerides content in liver as compared to probiotic alone. Our study demonstrated more pronounced reduction in hepatic steatosis and hepatic lipid accumulation after treatment with combination of alive probiotics and omega-3 as compared to probiotics alone.

Nanocrystalline cerium dioxide efficacy for prophylaxis of erosive and ulcerative lesions in the gastric mucosa of rats induced by stress.

In our previous works, the important therapeutic properties of nanocrystalline cerium dioxide such as strong antioxidant ability, prebiotical and antibiotic activity were shown. Such properties were obtained due to stabilization of nanoparticles with precise size 3-7nm. Such modification of nanocrystalline cerium dioxide has contributed to its remarkable efficacy and low toxicity. We have carried out the investigation of toxicity of the nanodrug and revealed that in the condition of the acute toxicity test, LD 50 was 2000mg/kg when it was administered per os. This indicator is approximately 1000 times greater than effective dose of the compound that proved the possibility of its usage for humans. Considering the strong antioxidant properties of this substance, we have performed the investigation of the influence of nanocrystalline cerium dioxide on the erosive-ulcerative lesions in gastric mucosa of rats induced by Selye's restraint stress. It was established that the studied compound significantly reduced the lesions area by 58.3% (p<0.05) induced by Selye's restraint stress. The attenuation of inflammation and decrease of lipid peroxidation in the conditions of gastric lesions and prophylactic administration of nanocrystalline cerium dioxide were shown. That was confirmed by the decrease of pro-inflammatory cytokines content (interleukin (IL) 1ß, 12B p40) and raise of anti-inflammatory cytokines content (IL-10 and transforming growth factor ß). Measurement of lipid peroxidation products has proved the antioxidant properties of nanocrystalline cerium dioxide as it decreased the content of conjugated dienes and thiobarbituric acid active products in the conditions of gastric ulceration induced by stress.

Prevention of NAFLD development in rats with obesity via the improvement of pro/antioxidant state by cerium dioxide nanoparticles.

BACKGROUND: One of the pathogenic mechanisms of the nonalcoholic fatty liver disease (NAFLD) is the accumulation of reactive oxygen species, which in turn aggravates the disease progress. We have investigated novel cerium dioxide nanoparticles (nCeO2) due to their promising antioxidant auto-regenerative ability and low toxicity. METHODS: 30 white male Wistar rats were divided into 3 groups: control, monosodium glutamate (MSG)-induced obesity and MSG treated with nCeO2 (MSG+nCeO2) groups. Newborn rats of control group were injected with saline (control). MSG- and MSG+nCeO2 groups were injected with MSG (4 mg/g concentration, 8 µl/g volume) between the 2nd and the 10th days of life subcutaneously [13]. At the age of 1 month, rats of group II were administered water 2.9 ml/kg orally, MSG+nCeO2 group received 1 mM solution of nCeO2 1 mg/kg orally. 4-months rats were sacrificed and the liver was harvested for histological and biochemical analysis. To assess the morphological changes in the liver we used NAS (NAFLD activity score). The content of lipid peroxidation products and enzymatic activity of superoxide dismutase (SOD) and catalase in the liver were studied by standard biochemical methods [Refs]. RESULTS: In 4-month rats we found significantly lower total score (1.3±0.26 vs 3.6±0.34, p<0.001), degree of steatosis (1.1±0.18 vs 2.1±0.18, p<0.001), manifestation of lobular inflammation (0.2±0.13 vs 1.2±0.2, p<0.001) and ballooning degeneration (0.0±0.0 vs 0.3±0.15, p=0.034) due to NAS in the nCeO2 group compared to the MSG-group. nCeO2 significantly decreased lipid peroxidation in the liver tissue, namely it reduced the conjugated dienes content by 27% (p<0.05), TBA-products - by 43% (p<0.05) and Schiff bases - by 21% (p<0.05). CONCLUSIONS: Due to its antioxidant properties nCeO2 significantly reduces the incidence of NASH and improves the main NAFLD histological features.

Comparative experimental investigation on the efficacy of mono- and multiprobiotic strains in non-alcoholic fatty liver disease prevention.

BACKGROUND: To investigate the efficacy of different probiotic strains, their combinations and forms (alive or lyophilized) in nonalcoholic fatty liver disease (NAFLD) prevention. METHODS: In this study, 70 rats have been used divided into 7 groups of 10 animals in each: I - intact rats, II-VII - rats with monosodium glutamate (MSG)-induced NAFLD. Rats with NAFLD were untreated (group II, MSG-obesity group) and treated with probiotics (groups III-VII). In order to develop NAFLD, newborn rats of groups II-VII were injected with a solution of monosodium glutamate (MSG) (4 mg/g) subcutaneously (s.c.) at 2nd,4th, 6th, 8th,10th postnatal day. The groups III-V received lyophilized monoprobiotics B. animalis VKL, B. animalis VKB, L.casei IMVB-7280, respectively. The group VI received 2.5 ml/kg of an aqueous solution of a mixture of the three probiotic strains (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, Bifidobacterium animalis VKB) at a dose of 50 mg/kg (5 × 10(9) CFU/kg) (g) (intragastrically). The group VII was treated with multiprobiotic "Symbiter" containing biomass of 14 alive probiotic strains (Lactobacillus + Lactococcus (6 × 10(10) CFU/g), Bifidobacterium (1 × 10(10)/g), Propionibacterium (3 × 10(10)/g), Acetobacter (1 × 10(6)/g)) at a dose of 140 mg/kg (1.4 × 10(10) CFU/kg). The treatment with probiotics was started at the age of 1 month. There were 3 courses of treatment, each included 2-week administration and 2-week break. All parameters were measured in 4-month aged rats. RESULTS: Introduction of MSG during the neonatal period leads to the NAFLD development in the 4-months old rats. For steatosis degree there was no significant difference between MSG-obesity group and lyophilized monocomponent probiotics groups (III-V). The highest manifestation of steatosis was observed for B. animalis VKL group (2.0 ± 0.25) as compared to B. animalis VKB (1.70 ± 0.21) and L. casei IMVB-7280 (1.80 ± 0.20). The steatosis score changes between all monoprobiotics groups (III-V) were insignificant. Administration from birth of both alive (VII) and lyophilized (VI) probiotic mixture lead to a significant decrease by 69.5 % (p < 0.001) and 43.5 % (p < 0.025) of steatosis score respectively as compared to the MSG-obesity group (2.3 ± 0.21 %). For both alive and lyophilized probiotic mixtures, reduction of lobular inflammation was observed. These histological data were confirmed by the significant decrease of total lipids and triglycerides content in the liver approximately by 22-25 % in groups treated with probiotic mixtures (VI, VII) compared to the MSG-obesity group. CONCLUSION: We established failure of NAFLD prevention with lyophilized monoprobiotic strains and the efficacy of probiotic mixture with the preference of alive probiotic strains.

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.

Short-term periodic consumption of multiprobiotic from childhood improves insulin sensitivity, prevents development of non-alcoholic fatty liver disease and adiposity in adult rats with glutamate-induced obesity.

BACKGROUND: Today the impairment of metabolism and obesity are being extensively investigated due to the significant increase of the prevalence of these diseases. There is scientific evidence that probiotics are beneficial for human health. Thus, the aim of the study was to investigate the effect of multiprobiotic "Symbiter acidophilic concentrated" on obesity parameters in the rats under experimental obesity. METHODS: The study was carried out on 60 newborn Wistar rats, divided into 3 groups, 20 animals in each (females - n = 10, males - n = 10): intact rats, monosodium glutamate (MSG-) and MSG + probiotic group. Rats of intact group were administered with saline (8 µl/g, subcutaneously (s.c.)). Newborns rats of MSG-group and MSG + probiotic group were injected with a solution of MSG (4.0 mg/g) s.c. at 2nd - 10th postnatal days. The MSG + probiotic group was treated with 140 mg/kg (1.4 × 10(10) CFU/kg) of multiprobiotic "Symbiter". MSG-group was treated with 2.5 ml/kg of water (per os) respectively. Administration was started at the age of 4 weeks just after wean and continued for 3 month intermittently alternating two-week course of introduction with two-week course of break. RESULTS: Neonatal treatment with MSG caused a stunted growth in both MSG-groups, which manifested with significantly smaller naso-anal length compared to adult intact rats. There was no significant difference in weight between intact and MSG-groups on 120th day. The adiponectin level in the serum of rats with MSG-induced obesity decreased by 2.43 times (p = 0.001) in males and 1.75 (p = 0.020) in females. Concentration of leptin in adipose tissue were significantly higher by 45.9% (p = 0.019) and 61.2% (p = 0.009) respectively in males and females compared to intact rats. Our study has indicated that daily oral administration of multiprobiotic to neonatal MSG-treated rats by 2-week courses led to significant reduce of total body and VAT weight with subsequent improvement in insulin sensitivity and prevention of non-alcoholic fatty liver (NAFLD) development. CONCLUSIONS: These results have shown that periodic treatment with multiprobiotic prevents the MSG-induced obesity and NAFLD development.

Pharmacological correction of stress-induced gastric ulceration by novel small-molecule agents with antioxidant profile.

This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

The efficacy of probiotics for monosodium glutamate-induced obesity: dietology concerns and opportunities for prevention.

INTRODUCTION: Obesity becomes endemic today. Monosodium glutamate was proved as obesogenic food additive. Probiotics are discussed to impact on obesity development. AIMS AND OBJECTIVES: The aim was to study the effects of probiotics on the development of monosodium glutamate (MSG)-induced obesity in rats. MATERIAL AND METHODS: We included 45 Wistar male rats and divided into three groups (n = 15). Newborn rats of 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. Within 4 months after birth, rats were on a standard diet. Group 3 received an aqueous solution of probiotics mixture (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, B. animalis VKB) at the dose of 5 × 109 CFU/kg (50 mg/kg) intragastrically. Administration of probiotics was started at the age of 4 weeks just after weaning and continued for 3 months during 2-week courses. Group 2 received intragastrically 2.5 ml/kg water. Organometric and biochemical parameters in all groups of rats were analyzed over 4 months. The concentration of adiponectin was determined in serum, and leptin - in adipose tissue. RESULTS: Administration of MSG led to the development of obesity in rats; body weight had increased by 7.9% vs controls (p < 0.05); body length had increased by 5.4% (p < 0.05). Body mass index and Lee index and visceral fat mass had increased (p < 0.001). Under the neonatal injection of MSG, the concentration of total cholesterol, triglycerides, VLDL cholesterol and LDL cholesterol significantly increased (p < 0.001), in comparison with controls. Adipose-derived hormones changed in MSG obesity rats: adiponectin decreased by 58.8% (p < 0.01), and leptin concentration in adipose tissue had increased by 74.7% (p < 0.01). The probiotic therapy of rats from group 3 prevented obesity development. Parameters of rats treated with probiotic mixture did not differ from that in the control. CONCLUSIONS: The introduction of MSG to newborn rats caused the obesity in adulthood. Periodic administration of probiotic mixture to rat injected with MSG neonatally resulted in recovery of lipid metabolism and prevention of the obesity development.

Modulation of protein tyrosine phosphorylation in gastric mucosa during re-epithelization processes.

AIM: To investigate the role of protein tyrosine phosphorylation in gastric wound formation and repair following ulceration. METHODS: Gastric lesions were induced in rats using restraint cold stress. To investigate the effect of oxidative and nitrosative cell stress on tyrosine phosphorylation during wound repair, total activity of protein tyrosine kinase (PTK), protein tyrosine phosphatase (PTP), antioxidant enzymes, nitric oxide synthase (NOS), 2',5'-oligoadenylate synthetase, hydroxyl radical and zinc levels were assayed in parallel. RESULTS: Ulcer provocation induced an immediate decrease in tyrosine kinase (40% in plasma membranes and 56% in cytosol, P < 0.05) and phosphatase activity (threefold in plasma membranes and 3.3-fold in cytosol), followed by 2.3-2.4-fold decrease (P < 0.05) in protein phosphotyrosine content in the gastric mucosa. Ulceration induced no immediate change in superoxide dismutase (SOD) activity, 30% increase (P < 0.05) in catalase activity, 2.3-fold inhibition (P < 0.05) of glutathione peroxidase, 3.3-fold increase (P < 0.05) in hydroxyl radical content, and 2.3-fold decrease (P < 0.05) in zinc level in gastric mucosa. NOS activity was three times higher in gastric mucosa cells after cold stress. Following ulceration, PTK activity increased in plasma membranes and reached a maximum on day 4 after stress (twofold increase, P < 0.05), but remained inhibited (1.6-3-fold decrease on days 3, 4 and 5, P < 0.05) in the cytosol. Tyrosine phosphatases remained inhibited both in membranes and cytosol (1.5-2.4-fold, P < 0.05). NOS activity remained increased on days 1, 2 and 3 (3.8-, 2.6-, 2.2-fold, respectively, P < 0.05). Activity of SOD increased 1.6 times (P < 0.05) days 4 and 5 after stress. Catalase activity normalized after day 2. Glutathione peroxidase activity and zinc level decreased (3.3- and 2-fold, respectively, P < 0.05) on the last day. Activity of 2',5'-oligoadenylate synthethase increased 2.8-fold (P < 0.05) at the beginning, and 1.6-2.3-fold (P < 0.05) during ulcer recuperation, and normalized on day 5, consistent with slowing of inflammation processes. CONCLUSION: These studies show diverse changes in total tyrosine kinase activity in gastric mucosa during the recovery process. Oxidative and nitrosative stress during lesion formation might lead to the observed reduction in tyrosine phosphorylation during ulceration.