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PloS One 2016The effects of spiramycin on adipogenesis and high fat diet (HFD)-induced obesity were investigated. Potential mechanisms contributing to these effects were elucidated....
The effects of spiramycin on adipogenesis and high fat diet (HFD)-induced obesity were investigated. Potential mechanisms contributing to these effects were elucidated. The inhibitory effect of spiramycin on adipocyte differentiation was assessed using 3T3-L1 preadipocyte cells, in which several parameters involved in AMPK signal pathways and lipid metabolism were examined. To further investigate the pharmacological effects of spiramycin in vivo, we examined several obesity-related parameters in HFD-induced obese mice. Spiramycin significantly inhibited preadipocyte differentiation by attenuating intracellular lipid accumulation. Spiramycin also reduced the expression of adipogenic master regulators (PPARγ, C/EBPα, and SREBP1c) and their downstream target genes (FAS, aP2, and GLUT4) in 3T3-L1 cells. In addition, AMPK phosphorylation was increased by spiramycin treatment in 3T3-L1 cells during early differentiation. Notably, HFD-induced obese mice administered spiramycin showed substantial decreases in body weight gain, serum leptin levels, adipose tissue mass, and hepatic lipid accumulation. Moreover, the decreased levels of GPT and GOT in the serum indicated that spiramycin attenuated hepatic injury caused by HFD. Taken together, these results demonstrate for the first time that spiramycin effectively attenuates HFD-induced obesity and hepatic steatosis by inhibiting adipogenesis.
Topics: 3T3-L1 Cells; AMP-Activated Protein Kinases; Adipogenesis; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; Diet, High-Fat; Gene Expression Regulation; Lipid Metabolism; Mice; Mice, Inbred C57BL; Obesity; PPAR gamma; Spiramycin; Sterol Regulatory Element Binding Protein 1
PubMed: 27398599
DOI: 10.1371/journal.pone.0158632 -
Tropical Medicine and Infectious Disease Jan 2023This study aimed to evaluate the prevalence of toxoplasmosis in pregnant women, as well as the general characteristics, clinical and laboratory findings, and pregnancy...
This study aimed to evaluate the prevalence of toxoplasmosis in pregnant women, as well as the general characteristics, clinical and laboratory findings, and pregnancy and fetal outcomes of pregnant women diagnosed with acute toxoplasma infection (ATI). The toxoplasma IgM, IgG, and IgG avidity test results of pregnant women who applied to our referral hospital between January 2016 and June 2022, and among them, those diagnosed with ATI, were analyzed. The 119 patients diagnosed with ATI during this time period were included for further analysis. The prevalence of toxoplasmosis in pregnant women was found to be 46.2%, and the rate of ATI was 4%. The total mother-to-child transmission rate was 5% (5/101). Congenital toxoplasmosis (CT) was observed in 1 (1.1%) child of the 87 pregnant women who received spiramycin prophylaxis, though it was found in 4 (30.8%) of the children of the 13 untreated mothers. With respect to prenatal treatment, CT rates were significantly higher in the children born to untreated mothers ( = 0.001). In conclusion, although toxoplasma seroprevalence was found to be high in our region, there was a paucity in diagnosis, follow-up, and treatment. Our findings support that prenatal spiramycin prophylaxis is effective in preventing the transmission of parasites from mother to child.
PubMed: 36668970
DOI: 10.3390/tropicalmed8010063 -
Canadian Family Physician Medecin de... Apr 2014Question Congenital toxoplasmosis is a dangerous fetal infection. Why is routine screening for Toxoplasma gondii infection during pregnancy not available for most...
Question Congenital toxoplasmosis is a dangerous fetal infection. Why is routine screening for Toxoplasma gondii infection during pregnancy not available for most Canadians? Answer Low prevalence of the infection, high cost associated with testing, low sensitivity of screening tests, false-positive test results, and limitations of treatment effectiveness are all cited as reasons for not routinely screening for T gondii infection in Canada. Currently, screening for the detection of T gondii is only performed in Nunavik and other parts of northern Quebec owing to the high prevalence of infection in this region. Congenital toxoplasmosis causes neurologic or ocular disease (leading to blindness), as well as cardiac and cerebral anomalies.
Topics: Anti-Bacterial Agents; Antiprotozoal Agents; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Mass Screening; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Spiramycin; Sulfadiazine; Toxoplasmosis; Toxoplasmosis, Congenital
PubMed: 24733322
DOI: No ID Found -
Food and Waterborne Parasitology Sep 2023The current study assessed the anti-parasitic impact of probiotics on infection either solely or challenged with diabetes in Swiss albino mice. The study design...
The current study assessed the anti-parasitic impact of probiotics on infection either solely or challenged with diabetes in Swiss albino mice. The study design encompassed group-A (diabetic), group-B (non-diabetic), and healthy controls (C). Each group was divided into infected-untreated (subgroup-1); infected and spiramycin-treated (subgroup-2); infected and probiotictreated (subgroup-3); infected and spiramycin+ probiotic-treated (subgroup-4). Diabetic-untreated animals exhibited acute toxoplasmosis and higher cerebral parasite load. Overall, various treatments reduced intestinal pathology, improved body weight, and decreased mortalities; nevertheless, probiotic + spiramycin exhibited significant differences. On day 7 post-infection both PD-1 and IL-17A demonstrated higher scores in the intestine of diabetic-untreated mice compared with non-diabetics and healthy control; whereas, claudin-1 revealed worsening expression. Likewise, on day 104 post-infection cerebral PD-1 and IL-17A showed increased expressions in diabetic animals. Overall, treatment modalities revealed lower scores of PD-1 and IL-17A in non-diabetic subgroups compared with diabetics. Intestinal and cerebral expressions of IL-17A and PD-1 demonstrated positive correlations with cerebral parasite load. In conclusion, toxoplasmosis when challenged with diabetes showed massive pathological features and higher parasite load in the cerebral tissues. Probiotics are a promising adjunct to spiramycin by ameliorating IL-17A and PD-1 in the intestinal and cerebral tissues, improving the intestinal expression of claudin-1, and efficiently reducing the cerebral parasite load.
PubMed: 37719029
DOI: 10.1016/j.fawpar.2023.e00201 -
European Review For Medical and... Mar 2023Through a cell culture test, we analyzed the cytotoxic effects of topical spiramycin on NIH/3T3 fibroblast cells.
OBJECTIVE
Through a cell culture test, we analyzed the cytotoxic effects of topical spiramycin on NIH/3T3 fibroblast cells.
MATERIALS AND METHODS
Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin was used for the growth of NIH/3T3 fibroblast cells in a 5% CO2 incubator. Spiramycin's cytotoxicity was measured using the MTT assay. 5,000 NIH/3T3 cells per well of a 96-well plate were seeded in each well, and the cells were treated with spiramycin (3.13-100 μM) for 24, 48 and 72 hours while the plates were incubated at 37°C in a humidified 5% CO2 atmosphere. First, 105 NIH/3T3 cells were seeded onto coverslips in 6-well plates for morphological analysis of both untreated and spiramycin-treated cells. For 24 hours, NIH/3T3 cells were exposed to a 100 μM dosage of spiramycin. The cells in the control group were grown in complete growth media alone.
RESULTS
Spiramycin was non-toxic to NIH/3T3 fibroblast cells in a MTT test. The concentration of spiramycin used to stimulate cell growth increased as the concentration was increased. After 24 and 48 hours of treatment with 100 μM NIH/3T3, the cells showed the most significant increase in size. Cell viability was shown to be significantly reduced at spiramycin doses of 50 and 100 μM. All MTT findings revealed that spiramycin enhanced cell viability and was not harmful to the fibroblast cells for short-term application of 24 and 48 hours but lowered the viability of fibroblast cells at the doses of 50 and 100 μM for long-term application duration of 72 hours. Confocal micrographs showed that spiramycin treatment did not affect the cytoskeleton or nucleus of fibroblast cells, in contrast to the control NIH/3T3 cells. Both untreated and treated with spiramycin, fibroblast cells were found to be fusiform and compact, with their nuclei remaining unaltered and unreduced in size.
CONCLUSIONS
It was concluded that spiramycin has a beneficial effect on fibroblast cells and is safe for use over short periods. Spiramycin reduced fibroblast cell viability when applied for 72 hours. Confocal micrographs showed that fibroblast cell skeletons and nuclei were unharmed and undamaged, that cell shapes were fusiform and compact, and that nuclei were neither broken nor shrunken. Topical spiramycin could be recommended for septorhinoplasty procedures due to anti-inflammatory effects for short-term usage if clinical trials will confirm experimental data.
Topics: Animals; Mice; Spiramycin; Carbon Dioxide; Fibroblasts; NIH 3T3 Cells; Cell Culture Techniques
PubMed: 36971220
DOI: 10.26355/eurrev_202303_31701 -
World Journal of Gastroenterology Apr 2023New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to...
BACKGROUND
New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin (CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects.
AIM
To obtain a deeper understanding of CAM, its distribution, metabolism and anti-inflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method.
METHODS
In this paper, the content of isovaleryl spiramycin III was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses.
RESULTS
The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4 (IL-4) levels in the lung and kidney and especially the liver and spleen; moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets, such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases.
CONCLUSION
We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.
Topics: Animals; Mice; Molecular Docking Simulation; Liver Neoplasms; Inflammation; Anti-Inflammatory Agents; Drugs, Chinese Herbal
PubMed: 37122599
DOI: 10.3748/wjg.v29.i14.2134 -
Journal of Parasitic Diseases :... Mar 2022The present study investigated the anti-Toxoplasma effect of chitosan nanoparticles [CS NPs], spiramycin, spiramycin co-administered with metronidazole and spiramycin-CS...
The present study investigated the anti-Toxoplasma effect of chitosan nanoparticles [CS NPs], spiramycin, spiramycin co-administered with metronidazole and spiramycin-CS NPs formulation on the parasite burden and histopathological changes in the liver, spleen and brain in experimentally infected mice Seventy male Swiss albino mice were classified into seven equal groups: healthy control (I), infected untreated control (II), infected group receiving CS NPs (III), spiramycin administered infected group (IV), infected group receiving spiramycin-metronidazole (V), infected receiving 400 mg/kg spiramycin-CS NPs (VI) and infected treated with spiramycin-loaded CS NPs 100 mg/kg (VII). All groups were inoculated intraperitoneally with 2500 T tachyzoites RH strain except the healthy control group. All groups were sacrificed on the 8th day after infection. Density of the parasite and histopathological examination of the liver, spleen and brain of all treated mice revealed reduction in the mean tachyzoites count as well as decreased inflammation, congestion and necrosis within tissue sections. Spiramycin-loaded NPs displayed the highest significant reduction in the pathological insult tailed by spiramycin-metronidazole and CS NPs. In conclusion, spiramycin-loaded CS NPs showed a promising synergistic combination in the treatment of the histopathology caused by toxoplasmosis.
PubMed: 35299902
DOI: 10.1007/s12639-021-01431-9 -
PLoS Neglected Tropical Diseases Mar 2022The novel formula of spiramycin/propolis loaded chitosan (CS)/alginate (Alg) nanoparticles (NPs) was assessed for Toxoplasma gondii (T. gondii) treatment in comparison...
The novel formula of spiramycin/propolis loaded chitosan (CS)/alginate (Alg) nanoparticles (NPs) was assessed for Toxoplasma gondii (T. gondii) treatment in comparison with the commercially available spiramycin regarding tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally by 2500 tachyzoites of the virulent T. gondii RH strain. The experimental groups were treated with oral spiramycin, propolis, CS/Alg NPs, spiramycin loaded CS/Alg NPs, propolis loaded CS/Alg NPs, and spiramycin/propolis loaded CS/Alg NPs. The results demonstrated that spiramycin/propolis loaded CS/Alg NPs exerted the longest survival time with no mortality on the sacrifice day (8th) in addition to representing the highest significant parasite percent reduction of (≥96% reduction) in liver, spleen and brain designating successful tissue penetration and BBB passage. Tachyzoites treated with spiramycin/propolis loaded CS/Alg NPs demonstrated the most disfigured rapturing organism via scanning electron microscope examination along with representing an overall remarkable improvement of the histopathological pictures of liver, spleen and brain. In conclusion, spiramycin/propolis loaded CS/Alg NPs showed the uppermost efficacy in the treatment of acute murine toxoplasmosis. The safe nature and the anti-parasitic effect of each of CS, Alg, spiramycin and propolis encourage the synergistic use of spiramycin/propolis loaded CS/Alg NPs as a potent treatment for human toxoplasmosis.
Topics: Alginates; Animals; Chitosan; Humans; Mice; Nanoparticles; Propolis; Spiramycin; Toxoplasma; Toxoplasmosis
PubMed: 35294434
DOI: 10.1371/journal.pntd.0010268 -
Pathogens (Basel, Switzerland) Sep 2021This research aimed to assess the pharmacokinetics/pharmacodynamics (PK/PD) and tissue residues of spiramycin in chickens. The PK of spiramycin were determined in 12...
This research aimed to assess the pharmacokinetics/pharmacodynamics (PK/PD) and tissue residues of spiramycin in chickens. The PK of spiramycin were determined in 12 chickens using a parallel study design in which each group of chickens ( = 6) received a single dose of spiramycin at 17 mg/kg intravenously (IV) or orally. Plasma samples were collected at assigned times for up to 48 h to measure spiramycin concentrations. Additionally, a tissue depletion study was performed in 42 chickens receiving spiramycin at 17 mg/kg/day orally for 7 days. The area under the plasma concentration-time curve values were 29.94 ± 4.74 and 23.11 ± 1.83 µg*h/mL after IV and oral administrations, respectively. The oral bioavailability was 77.18%. The computed withdrawal periods of spiramycin were 11, 10, and 7 days for liver, muscle, and skin and fat, respectively. The minimum inhibitory concentration for spiramycin against () strain 1853 was 0.0625 µg/mL. Using the PK/PD integration, the appropriate oral dose of spiramycin against was estimated to be 15.6 mg/kg. Thus, we recommend an oral dose of 15.6 mg spiramycin/kg against in chickens and a withdrawal period of 11 days following oral treatment with 17 mg spiramycin/kg/day for 7 days.
PubMed: 34684187
DOI: 10.3390/pathogens10101238 -
British Medical Journal Mar 1956
Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Dermatologic Agents; Pneumonia; Spiramycin
PubMed: 13293407
DOI: No ID Found