Oleksandr Virchenko

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

IntroductionObesity becomes endemic today. Monosodium glutamate was proved as obesogenic food additive. Probiotics are discussed to impact on obesity development.Aims and objectivesThe aim was to study the effects of probiotics on the development of monosodium glutamate (MSG)-induced obesity in rats.Material and methodsWe included 45 Wistar male rats and divided into three groups (nu2009=u200915). Newborn rats of group 1 (control) received subcutaneously 8xa0μl/g saline. Group 2 received 3 to 4xa0mg/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 5u2009×u2009109xa0CFU/kg (50xa0mg/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 2.5xa0ml/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.ResultsAdministration 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.ConclusionsThe 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.

Pathophysiological role of host microbiota in the development of obesity

Overweight and obesity increase the risk for a number of diseases, namely, cardiovascular diseases, type 2 diabetes, dyslipidemia, premature death, non-alcoholic fatty liver disease as well as different types of cancer. Approximately 1.7 billion people in the world suffer from being overweight, most notably in developed countries. Current research efforts have focused on host and environmental factors that may affect energy balance. It was hypothesized that a microbiota profile specific to an obese host with increased energy-yielding behavior may exist. Consequently, the gut microbiota is becoming of significant research interest in relation to obesity in an attempt to better understand the aetiology of obesity and to develop new methods of its prevention and treatment. Alteration of microbiota composition may stimulate development of obesity and other metabolic diseases via several mechanisms: increasing gut permeability with subsequent metabolic inflammation; increasing energy harvest from the diet; impairing short-chain fatty acids synthesis; and altering bile acids metabolism and FXR/TGR5 signaling. Prebiotics and probiotics have physiologic functions that contribute to the health of gut microbiota, maintenance of a healthy body weight and control of factors associated with obesity through their effects on mechanisms that control food intake, body weight, gut microbiota and inflammatory processes.

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.

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

BackgroundTo investigate the efficacy of different probiotic strains, their combinations and forms (alive or lyophilized) in nonalcoholic fatty liver disease (NAFLD) prevention.MethodsIn 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) (4xa0mg/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 2.5xa0ml/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 50xa0mg/kg (5u2009×u2009109xa0CFU/kg) (g) (intragastrically). The group VII was treated with multiprobiotic “Symbiter” containing biomass of 14 alive probiotic strains (Lactobacillusu2009+u2009Lactococcus (6u2009×u20091010xa0CFU/g), Bifidobacterium (1u2009×u20091010/g), Propionibacterium (3u2009×u20091010/g), Acetobacter (1u2009×u2009106/g)) at a dose of 140xa0mg/kg (1.4u2009×u20091010xa0CFU/kg). The treatment with probiotics was started at the age of 1xa0month. There were 3 courses of treatment, each included 2-week administration and 2-week break. All parameters were measured in 4-month aged rats.ResultsIntroduction 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 (2.0u2009±u20090.25) as compared to B. animalis VKB (1.70u2009±u20090.21) and L. casei IMVB-7280 (1.80u2009±u20090.20). 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 69.5xa0% (pu2009<u20090.001) and 43.5xa0% (pu2009<u20090.025) of steatosis score respectively as compared to the MSG-obesity group (2.3u2009±u20090.21xa0%). 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 22–25xa0% in groups treated with probiotic mixtures (VI, VII) compared to the MSG-obesity group.ConclusionWe established failure of NAFLD prevention with lyophilized monoprobiotic strains and the efficacy of probiotic mixture with the preference of alive probiotic strains.

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 1u2009mg/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

BACKGROUNDnObesity 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.nnnMETHODSnThe 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.nnnRESULTSnWe 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.nnnCONCLUSIONnThe 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.