Effect of spiramycin versus aminoguanidine and their combined use in experimental toxoplasmosis

Omar, Marwa; Abaza, Beessa E.; Mousa, Esraa; Ibrahim, Shereen Mahmoud; Rashed, Hayam E.; Farag, Tahani Ismail

doi:10.1007/s12639-021-01396-9

Cited by 15 publications

(11 citation statements)

References 45 publications

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“…Similarly, severe architectural disorder, inflammatory cell infiltration, notable fatty alteration, and fibrosis in T. gondii –infected liver sections were reported [ 57 – 59 ]. Notably, some researchers recorded negative results to Toxoplasma reproduction in hepatic cells [ 60 ].…”

Section: Discussionmentioning

confidence: 62%

“…In agreement with our observation, liver tissues from the infected untreated group sacrificed eight weeks PI revealed strong iNOS expression, indicating increased NO levels in this tissue. This finding was associated with significant histopathological insult in liver parenchyma [ 59 ]. It has been reported that the pathophysiology of toxoplasmosis is related to the increased risk of oxidative stress in host cells due to the activation of inflammatory response against the parasite [ 104 ].…”

Section: Discussionmentioning

confidence: 99%

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Histopathological, Immunohistochemical and Biochemical Studies of Murine Hepatosplenic Tissues Affected by Chronic Toxoplasmosis

Yahia

Etewa

Saleh

et al. 2022

Journal of Parasitology Research

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Toxoplasmosis is a serious health problem in humans and animals resulting from obligatory intracellular invasion of reticuloendothelial tissue by Toxoplasma gondii. The profound pathologic effect of toxoplasmosis is confined to nervous tissue, but many other organs, including the liver and spleen, are insulted. Many molecules like caspase-3, CD3, and CD138 are implicated in the tissue immune response in a trial to alleviate hazardous toxoplasmosis impact. This study aimed to investigate the effect of chronic toxoplasmosis on the liver and spleen tissues of mice using biochemical and histopathological techniques and to detect the activity and level of expression of caspase-3, CD3, and CD138 in these tissues using immunohistochemical labeling. Compared with normal control, altered normal histological features accompanied by inflammatory reaction were recorded in hepatosplenic reticuloendothelial tissues in chronically infected mice. The biochemical profile of the liver has been changed in the form of increased liver enzymes, and oxidative stress has been evidenced by elevated nitric oxide (NO) concentration in liver homogenate. The levels of caspase3, CD3, and CD138 were markedly expressed in the liver and spleen of infected mice. Our findings revealed the persistent effect of latent toxoplasmosis on the host’s histological architecture, metabolic, and immunological profile, creating a continued challenging host-parasite relationship.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Histopathological, Immunohistochemical and Biochemical Studies of Murine Hepatosplenic Tissues Affected by Chronic Toxoplasmosis

Yahia

Etewa

Saleh

et al. 2022

Journal of Parasitology Research

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“…Aminoguanidine (AG, NO synthase inhibitors) with the ability to inhibit NO synthetase and can effectively inhibit NO production induced by LPS. 55,56 To investigate whether this fluorescence phenomenon can be ascribed to LPS promoting endogenous NO and probe response in cells, we treated the cells with LPS and AG and subsequently incubated them with NFL-NH 2 probe for fluorescence imaging. The cells treated with LPS + AG showed a weaker green fluorescent signal compared to the inflammatory cells treated with LPS alone.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Mitochondrial-Targeted Ratiometric Near-Infrared Fluorescence Probe for Monitoring Nitric Oxide in Rheumatoid Arthritis

Han,

Sun,

Zhao

et al. 2024

J. Med. Chem.

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Rheumatoid arthritis (RA) is a destructive autoimmune disease, where nitric oxide (NO) is closely implicated in the inflammatory processes of RA. Therefore, direct visualization of NO is essential to assess the pathological changes in RA. Herein, a mitochondrial-targeted near-infrared ratiometric fluorescent probe (NFL-NH 2 ), based on the intramolecular charge transfer effect, was synthesized and applied to monitor the changes of NO content in early RA. Specially, probe NFL-NH 2 showed a 44-fold fluorescent intensity ratio (I 705 /I 780 ) response toward NO with a detection limit of 0.536 nM, enabling qualitative and quantitative analysis of NO. Additionally, NFL-NH 2 can accurately target mitochondria and sensitively detect exogenous and endogenous NO in RAW 264.7 cells. Notably, in vivo RA monitoring assays demonstrated that NFL-NH 2 can rapidly detect NO levels associated with the inflammatory damage degree in RA mice models by ratiometric fluorescence imaging. These results validate that NFL-NH 2 holds significant potential for diagnosing NO-mediated RA diseases.

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“…In this study, we confirmed the possibility of applying an old weapon, spiramycin, to various inflammatory diseases, the new enemy. Spiramycin has been shown to exhibit anti-bacterial, anti-viral, and anti-parasitic activities [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. However, no study has reported the anti-inflammatory potential of spiramycin in LPS-induced macrophage RAW 264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Spiramycin is a 16-membered ring macrolide antibiotic that was first discovered 70 years ago in a culture medium of Streptomyces ambofaciens in 1952 ( Figure 1 ). The antibiotic action of spiramycin, which inhibits protein synthesis in bacterial cells during translocation, has high antimicrobial activity against Gram-positive bacteria and mycoplasma species, and is widely used to treat toxoplasmosis and other soft-tissue infections in cattle, pigs, poultry, and sheep [ 6 , 7 , 8 ]. Spiramycin is prescribed in some countries for various odor-causing infections including periodontitis [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of Spiramycin in LPS-Activated RAW 264.7 Macrophages

Kang

Hyun

2022

Molecules

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Drug repurposing is a simple concept with a long history, and is a paradigm shift that can significantly reduce the costs and accelerate the process of bringing a new small-molecule drug into clinical practice. We attempted to uncover a new application of spiramycin, an old medication that was classically prescribed for toxoplasmosis and various other soft-tissue infections; specifically, we initiated a study on the anti-inflammatory capacity of spiramycin. For this purpose, we used murine macrophage RAW 264.7 as a model for this experiment and investigated the anti-inflammatory effects of spiramycin by inhibiting the production of pro-inflammatory mediators and cytokines. In the present study, we demonstrated that spiramycin significantly decreased nitric oxide (NO), interleukin (IL)-1β, and IL-6 levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Spiramycin also inhibited the expression of NO synthase (iNOS), potentially explaining the spiramycin-induced decrease in NO production. In addition, spiramycin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs); extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase (JNK) as well as the inactivation and subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicated that spiramycin attenuates macrophages’ secretion of IL-6, IL-1β, and NO, inducing iNOS expression via the inhibition of the NF-κB and MAPK signaling pathways. Finally, we tested the potential application of spiramycin as a topical material by human skin primary irritation tests. It was performed on the normal skin (upper back) of 31 volunteers to determine whether 100 μM and μM of spiramycin had irritation or sensitization potential. In these assays, spiramycin did not induce any adverse reactions. In conclusion, our results demonstrate that spiramycin can effectively attenuate the activation of macrophages, suggesting that spiramycin could be a potential candidate for drug repositioning as a topical anti-inflammatory agent.

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Effect of spiramycin versus aminoguanidine and their combined use in experimental toxoplasmosis

Cited by 15 publications

References 45 publications

Histopathological, Immunohistochemical and Biochemical Studies of Murine Hepatosplenic Tissues Affected by Chronic Toxoplasmosis

Histopathological, Immunohistochemical and Biochemical Studies of Murine Hepatosplenic Tissues Affected by Chronic Toxoplasmosis

Mitochondrial-Targeted Ratiometric Near-Infrared Fluorescence Probe for Monitoring Nitric Oxide in Rheumatoid Arthritis

Anti-Inflammatory Effects of Spiramycin in LPS-Activated RAW 264.7 Macrophages

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