Tetyana Beregova

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

BackgroundToday 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.MethodsThe 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 × 1010 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.ResultsNeonatal 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.ConclusionsThese results have shown that periodic treatment with multiprobiotic prevents the MSG-induced obesity and NAFLD development.

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.

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.

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)-1β, IL-12Bp40, interferon-γ (INF-γ)) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor-β (TGF-β)) 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-1β, IL-12Bp40) in rat serum and restored the level of anti-inflammatory cytokines (IL-4, IL-10, TGF-β) 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.

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

To evaluate the therapeutic effect of a probiotic cocktail containing Lactobacilli, Bifidobacteria and Streptococcus thermophilus on non‐alcoholic steatohepatitis (NASH).

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 Selyes restraint stress. It was established that the studied compound significantly reduced the lesions area by 58.3% (p<0.05) induced by Selyes 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) 1β, 12B p40) and raise of anti-inflammatory cytokines content (IL-10 and transforming growth factor β). 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.

Multiprobiotic therapy from childhood prevents the development of nonalcoholic fatty liver disease in adult monosodium glutamate-induced obese rats

Abstract Considering the association between microflora and obesity, and the significantly higher prevalence of non-alcoholic fatty liver disease (NAFLD) in obese people, the aim of our study was to investigate the preventive effect of multiprobiotics on the monosodium glutamate (MSG) induced NAFLD model, in rats. The work was carried out on 60 rats placed into three groups: the Control group, the MSG-group and the MSG-probiotic group. The MSG-group and the MSG-probiotic group were injected with 4 mg/g of MSG subcutaneously neonatally on the 2nd-10th days of life. The MSG-probiotic rats were also treated with 140 mg/kg of multiprobiotic “Symbiter” from the 4th week of life. In the 4-month-old rats, biochemical and morphological changes in liver were assessed, and steatosis was confirmed by the NAFLD activity score (NAS). Our results reveal that the multiprobiotic lowered total NAS, the degree of steatosis and the liver lobular inflammation caused by MSG. It also brought about decreased liver total lipids and triglycerids content, as well as decreased visceral adipose tissue mass. However, there was no difference in the liver serum biochemical indicators between all experimental groups. The obtained data does suggest the efficacy of probiotics in the prevention of NAFLD.

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)-1β, IL-12Bp40, interferon (INF)-γ) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor (TGF)-β) 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-1β in rat serum and restored the level of anti-inflammatory cytokines (IL-10, TGF-β) 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.

Improvement of the modeling and diagnosis of hepatic encephalopathy in rats

One of the challenging problem in gastroenterology is the treatment of liver cirrhosis (LC) and hepatic encephalopathy (HE) as one of its dangerous complications [1,2]. HE is the frequent disorder that hits approximately 50-80% of cirrhotic patients [3,4]. HE is a complex, reversible neuropsychiatric syndrome, complicating the course of liver disease. In recent guidelines published jointly by the European and American Associations for the Study of the Liver, HE was defined as “brain dysfunction caused by liver insufficiency or portal systemic shunting” [5]. Despite the fact that the syndrome was probably recognized thousands of years ago, the exact pathogenesis and diagnosis remain not enough comprehensible [6]. The pathogenesis is thought to be attributable to both neuro-chemical and neurophysiological disorders of the brain. The essentially reversible nature suggests a metabolic cause [6]. This pathology is associated with progressive dystrophy of brain tissue and can lead to patients disability [7,1]. Despite agreement between investigators that HE warrants further investigation and probably screening and treatment, there is little consensus as to the optimal instruments Volume 3 Issue 3 2017

Tlr2, Tjp1 genes expression during wound healing dynamics – with melanin treatment

Abstract Wound healing is the complex and dynamic process of replacing devitalized and missing cellular structures and tissue layers. We have previously shown that melanin, herein, produced by the Antarctic black yeast fungi Pseudonadsoniella brunea (Nadsoniella nigra sp. X-1), has expressed a cyto-protective effect, promoted rapid wound healing of various ethiology and can be offered as a new dermatropic drug. The current study was conducted on a rat model of purulent necrotic wound. In each model, one group was a control, while in the others, wound healing occurred without drug application or with administration of 0,5% carbopol or with both 0,5% carbopol and 0,1% melanin. The pro-oxidant-antioxidant balance in skin gomogenate in dynamics on 3, 6, 9, 14 and day of full epithelization was estimated using the spectrophotometric biochemical method. Moreover, so as to understand the role played by the Tlr2 and Tjp1 in the process of wound healing and scar formation, Tlr2, Tjp1gene expression and genetic mRNA was determined with quantitative RT-PCR. The application of our pharmacological composition stimulated the decrease of Tlr2 and Tjp1 gene expression against the background of suppression of free radical processes (reduction of superoxide anion radical content) with epithelization and without scarring. The results of this study have shown the positive effects of melanin on wound healing. The obtained results indicate the advisability of applying melanin for the treatment of inflammatory processes.