The effect of intranasally administered TLR3 agonist larifan on metabolic profile of microglial cells in rat with C6 glioma

Glioma-associated microglia/macrophages (GAM) represent an attractive therapeutic target for the development of the alternative methodology in the treatment of gliomas. This study was aimed to investigate the effect of intranasally administered TLR3 agonist Larifan on microglial cell metabolic profile in rats with C6 glioma. Our results demonstrate progressive generation microglial cell population with immunosuppressive and pro-inflammatory properties in C6 glioma-bearing brain. Intranasally delivered TLR3 agonist is capable to abrogate the creation of this pro-tumoral immune infiltrates, probably, through the effect on myeloid-derived suppressor cells, and can be considered as a promising agent for glioma therapy aimed the GAM re-education

PHYTOCHEMICAL SCREENING OF POLYHERBAL COMPOSITION BASED ON Portulaca oleracea AND IT’S EFFECT ON MACROPHAGE OXIDATIVE METABOLISM

The aim of the work was to explore phytochemical characteristics of water extract from polyherbal composition based on P. oleracea and it’s effect on oxidative metabolism of murine peritoneal macrophages. The qualitative phytochemical analysis was conducted by colorimetric method. Quantitative analysis of phenols was performed in the test with gallic acid as a standard. Murine peritoneal macrophages were isolated without previous sensitization. Leukotoxicity of the water extract from polyherbal composition leukotoxicity was evaluated in MTT test. Reactive oxygen species generation was assayed by the nitroblue tetrazolium reduction method. Phytochemical analysis revealed the presence of water-soluble and insoluble phenols, tannins, saponins, flavonoids, cardiac glycosides and coumarins in the studied plant mixture. The water extract from polyherbal composition used in a range of concentration 1–1000 μg/ml (lyophilisate in distilled H2O) didn’t exhibit any toxic effects on murine peritoneal macrophages. Water extract from polyherbal composition caused statistically significant dose-dependent increase in oxidative metabolism of murine peritoneal suggest modulatory effect of studied water extract from polyherbal composition on innate immunity cells

Systemic inflammation biomarkers in 6-OHDA- and LPS-induced Parkinson’s disease in rats

Hematological and immunological markers of systemic inflammation were studied in 6-hydroxydopamine (6-OHDA)- and lipopolysaccharide (LPS)-induced models of Parkinson’s disease (PD). Experiments were carried out on adult male Wistar rats: 1 – intact animals; 2 – sham-operated animals and 3 – 6-OHDA- and LPS-lesioned animals. PD development was confirmed by the results of behavioral testing (apomorphine test, open field test) and immunohistochemical detection of the loss of dopaminergic neurons. Hematological indices (complete blood count and differential leukocyte count (DLC)) were examined using hematological analyser. Immunological indices included phenotypic (CD206 and CD80/86) and metabolic (oxidative metabolism and phagocytic activity) characteristics of circulating monocytes (Mo) and granulocytes (Gr), which were determined by flow cytometry, as well as plasma levels of C-reactive protein, which were determined by ELISA. LPS-induced PD was associated with neutrophilia, 1.9 times increased neutrophil-to-lymphocyte ratio, 3 times increased platelet-to-lymphocyte ratio, and 3 times increased systemic immune inflammation index as compared to intact animals. Functional profile of circulating phagocytes from LPS-lesioned animals was characterized by the pro-inflammtory metabolic shift, as was indicated by 5 times increased oxidative metabolism indices and up-regulated CD80/86 expression along with decreased phagocytic activity and CD206 expression. 6-OHDA-lesioned rats demonstrated decreased DLC indices as compared to intact and sham-operated rats. Functional profile of circulating phagocytes in this model was characterized by anti-inflammatory shift. The results obtained from this study demonstrated that stereotaxic LPS-induced PD is appropriate rodent model for the study of systemic inflammation which is inherent for the disease pathophysiology

The effect of multiprobiotic “Symbiter acidophilus” on the intestinal microflora and functional activity of peritoneal macrophages in rats with glutamate-induced obesity

Significant decrease in number of members of Lactobacillus genus and the increase in the number of types of aerobic microorganisms E. coli and S. aureus in the faeces and in the biopsy of colonic wall were observed in rats with monosodium glutamate-induced obesity. Treatment with “Symbiter acidophilic” prevented of microbial landscape quantitative changes associated with the obesity. Immunomodulating effect of probiotic was characterized by gender differences in animals with obesity. The treatment with “Symbiter acidophilic” was accompanied by the preclusion of peritoneal phagocyte functional activity disorders and mononuclear phagocytes recruitment to the peritoneal cavity of female rats. Positive changes in the microbiota and immune reactivity in the peritoneal cavity were associated with decreased fat weight of various localizations in female rats who received multiprobiotic. Treatment with “Symbiter acidophilic” was also accompanied by the recruitment of mononuclear cells to the peritoneal cavity in male rats. However, the metabolic profile of these cells was characterized by proinflammatory directedness. The weight index in group of male rats treated with probiotics did not differ from that in the obese male rats