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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 -
Journal of Parasitic Diseases :... Dec 2021Toxoplasmosis is one of the widest spread parasitic infections which is caused by protozoon. Many experimental studies have evaluated the effect of aminoguanidine upon...
Toxoplasmosis is one of the widest spread parasitic infections which is caused by protozoon. Many experimental studies have evaluated the effect of aminoguanidine upon parasitic load and inflammatory process. However, few reports have illustrated the impact of combining aminoguanidine with spiramycin in the treatment of toxoplasmosis. Therefore, our study aimed to explore the possible effects of spiramycin used alone and combined with aminoguanidine against the avirulent (ME49) strain in experimental toxoplasmosis. Fifty-five Swiss albino mice were included in the study and were divided into five groups: (GI): non-infected control group; (GII): infected untreated control group; (GIII): infected- spiramycin treated group; (GIV): infected-aminoguanidine treated group; (GV): infected and received combination of spiramycin and aminoguanidine. Obtained results exhibited a significant increase in brain cysts numbers in aminoguanidine treated groups compared to infected untreated control groups. Histopathological studies denoted that combination between spiramycin and aminoguanidine improved the pathological features only in liver and heart tissues of the studied groups. Moreover, it was noticed that spiramycin administered alone had no effect on nitric oxide expression, whereas its combination with aminoguanidine had an inhibitory effect on inducible nitric oxide synthase enzyme in brain, liver and heart tissues of different study groups. In conclusion, the combination of spiramycin and aminoguanidine significantly reduced the parasitic burden, yet, it failed to resolve the pathological sequels in brain tissues of infected mice.
PubMed: 34789985
DOI: 10.1007/s12639-021-01396-9 -
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 -
Prenatal Diagnosis Dec 2020Although prenatal diagnosis and prenatal and neonatal therapy of congenital toxoplasmosis are available, there is controversy concerning the effectiveness of prophylaxis... (Review)
Review
Although prenatal diagnosis and prenatal and neonatal therapy of congenital toxoplasmosis are available, there is controversy concerning the effectiveness of prophylaxis to prevent placental transmission. Experimental, parasitological, and clinical data suggest a "window of opportunity" following maternal infection. Among medications active against Toxoplasma gondii, mainly spiramycin (Spy) and pyrimethamine + sulfonamide combinations (P-S) have been evaluated. Results from observational studies suffered treatment bias, since prescriptions differed according to the gestational age at seroconversion, which is the major risk factor for transmission, and many lacked precise timing. Some large retrospective studies found no difference in transmission according to prophylactic treatment, but transmission was lower when treatment started promptly after maternal seroconversion. A few recent studies adjusting for timing of infection observed lower transmission in case of P-S than other or no prophylaxis. In the only randomized controlled trial, transmission was lower with P-S than S (18.5% vs 30%, P = .147); this association was strengthened when the treatment was started within 3 weeks of seroconversion, and the incidence of fetal cerebral ultrasound signs was significantly reduced in the P-S group. Rapid initiation of prophylactic therapy following maternal infection, which is usually asymptomatic, requires systematic screening for maternal seroconversion during pregnancy.
Topics: Antiprotozoal Agents; Asymptomatic Infections; Drug Therapy, Combination; Female; Global Health; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Patient Safety; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Toxoplasmosis, Congenital
PubMed: 32453454
DOI: 10.1002/pd.5758 -
Critical Reviews in Analytical Chemistry 2023Veterinary medicinal products (VMPs) are used for the prevention and treatment of diseases in animals. The safety and efficacy of these products must be proven by... (Review)
Review
Veterinary medicinal products (VMPs) are used for the prevention and treatment of diseases in animals. The safety and efficacy of these products must be proven by quality control tests. Special attention should be paid to veterinary antimicrobials medicines (VAMs), as changes in their potency can compromise pharmacotherapeutic treatment and contribute to microbial resistance. The aim of this work was to review the analytical methods available for assessing the quality of VAMs, to analyze regulatory issues and quality control programs. The review was performed on selected papers in the PubMed, ScienceDirect, Scopus and Virtual Health Library databases, between 2005 and 2020. After applying exclusion criteria, 19 studies were obtained. Of the analytical studies, the majority (61.54%) used the HPLC technique. In addition, methods by CE (15.39%) and by SPM, FIA and microbiological assay (7.69% each) were found. In studies of monitoring of VAMs available on the market, changes in tylosin, spiramycin, ampicillin, tetracyclines and penicillins were observed. This is worrying, as these quality deviations can contribute to the development of resistant microorganisms. Although international efforts have been implemented at the regulatory level to ensure the quality of VAMs, it was realized with this study that there is much to evolve in the development of new analytical methods and in monitoring the quality of VAMs. With this, it is expected that this study will instigate scientists in the analytical, regulatory, microbiological and veterinary fields to develop new research so that the demands necessary to guarantee the quality of VAMs are increasingly met.
Topics: Animals; Anti-Infective Agents; Anti-Bacterial Agents; Tylosin; Veterinary Drugs; Quality Control
PubMed: 34396844
DOI: 10.1080/10408347.2021.1964342 -
Comparative Biochemistry and... Jul 2022Over the last decade, pollution of plastics and antibiotics has increased in its threat to the environment and human health. However, very limited information is...
Over the last decade, pollution of plastics and antibiotics has increased in its threat to the environment and human health. However, very limited information is available concerning impact of co-presence of plastics and antibiotics on environment and human health. Moreover, the potential ingestion and inhalation of nano(micro)plastics due to the disposable materials has dramatically increased. With the outbreak and spread of the COVID-19 in the world, disposable surgical masks and plastic bottles have been widely used by the public, and their rapid use and improper dispensing can cause to increase plastic pollution risk on human. However, impacts of co-presence of nano(micro)plastics and antibiotics on pathogens have yet been demonstrated. Therefore, this study aims to investigate the impact the individual and combined influences of nano-sized plastics (surgical mask and plastic bottles) and antibiotics (amoxicillin and spiramycin) towards the main susceptible bacterium (Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa) by microbial activity, biofilm formation and their biochemical characteristics. The results showed that antimicrobial efficiencies of the tested antibiotics were reduced (approximately 10-98%) with the plastics. Moreover, the biochemical pathways of the microbial activity changed by the plastics entrance. Polymer structure and sorption play the role on the reduction in the inhibition of pathogens. In the meantime, the biofilm formation changed and characteristic of the extracellular polymeric substance with the co-presence of plastics and antibiotics mostly depended on the polymer structure, exposure time and sorption.
Topics: Anti-Bacterial Agents; COVID-19; Escherichia coli; Extracellular Polymeric Substance Matrix; Humans; Masks; Microplastics; Plastics; Polymers; SARS-CoV-2
PubMed: 35381365
DOI: 10.1016/j.cbpc.2022.109340 -
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 -
Microbiological Research Nov 2020Bitespiramycin (biotechnological spiramycin, Bsm) is a new 16-membered macrolide antibiotic produced by Streptomyces spiramyceticus WSJ-1 integrated exogenous genes. The...
Bitespiramycin (biotechnological spiramycin, Bsm) is a new 16-membered macrolide antibiotic produced by Streptomyces spiramyceticus WSJ-1 integrated exogenous genes. The gene cluster for Bsm biosynthesis consists of two parts: spiramycin biosynthetic gene cluster (92 kb) and two exogenous genes including 4"-O-isovaleryltransferase gene (ist) and a positive regulatory gene (acyB2) from S. thermotolerans. Four putative regulatory genes, bsm2, bsm23, bsm27 and bsm42, were identified by sequence analysis in the spiramycin gene cluster. The inactivation of bsm23 or bsm42 in S. spiramyceticus eliminated spiramycin production, while the deletion of bsm2 and bsm27 did not abolish spiramycin biosynthesis. The acyB2 gene, homologous with bsm42 gene, cannot recover the spiramycin production in Δbsm42 mutant. The high expression of bsm42 significantly increased the spiramycin production, but overexpression of bsm23 inhibited its production in Δbsm23 and wild-type strain. Bsm23 was shown to be involved in the regulation of the expression of bsm42 and acyB2 by electrophoretic mobility shift assays. The bsm42 gene was also positive regulator for ist expression inferred from the improved yield of 4"-isovalerylspiramycins in the S. lividans TK24 biotransformation test, but adding bsm23 decreased the production of 4''-isovalerylspiramycins. These results demonstrated Bsm42 was a pathway-specific activator for spiramycin or Bsm biosynthesis, but overexpression of Bsm23 alone was adverse to produce these antibiotics although Bsm23 was essential for positive regulation of spiramycin production.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Biosynthetic Pathways; Biotransformation; Gene Expression Regulation, Bacterial; Genes, Regulator; Multigene Family; Spiramycin; Streptomyces
PubMed: 32622100
DOI: 10.1016/j.micres.2020.126532