Role of Rifampin in Reducing Inflammation and Neuronal Damage in Childhood Bacterial Meningitis

Uppal, Lipi; Singhi, Sunit; Singhi, Pratibha; Aggarwal, Ritu

doi:10.1097/inf.0000000000001513

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…So far, a variety of therapeutic agents have been reported to reduce sebum production, inflammation, and bacterial counts (Becerro de Bengoa Vallejo, Losa Iglesias, Alou Cervera, Sevillano Fernandez, & Prieto, 2009;Inui, Aoshima, Ito, Kobuko, & Itami, 2012;Uppal, Singhi, Singhi, & Aggarwal, 2017). These chemicals are used either topically or systemically based on the severity of the acne lesion.…”

Section: R E T R a C T E Dmentioning

confidence: 99%

Retracted: Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with dual antibacterial and anti‐inflammatory action

Yang

Wang

et al. 2019

British J Pharmacology

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Background and Purpose: Propionibacterium acnes (P. acnes) is a Gram-positive bacterium associated with the skin disorder acne. In this study, we determined the importance of fatty acids in the life habitat of P. acnes; we tested our lipopeptide library in an attempt to create potent P. acnes-specific antimicrobial agents. Experimental Approach: Antimicrobial activity was determined by the minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore the mode of action. RAW264.7 cells respectively stimulated with LPS and P. acnes were used to measure the anti-inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti-inflammatory effects of the peptides tested in vivo. Key Results: The most potent candidate, C16-KWKW, was observed to be more active against P. acnes, with an MIC of 2 μg•ml −1 , than against other non-targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16-KWKW was observed to be through interference with the integrity of bacterial membrane, thereby impairing membrane permeability and causing leakage of the inner contents of bacterial cells. In addition, C16-KWKW inhibited the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α, and inducible NOS, stimulated by both LPS and P. acnes, thus showing potential anti-inflammatory activity, which was further assessed in animal studies in vivo. Conclusions and Implications: C16-KWKW is a lipopeptide displaying both anti-P. acnes and anti-inflammatory effects in vitro and in vivo, and exhibits potential as a treatment for acne vulgaris induced by P. acnes. 1 | INTRODUCTION Acne vulgaris is a chronic skin disorder that often develops on the face and upper trunk and is characterized by the formation of comedones, papules, nodules, pustules, and cysts (Aslam, Fleischer, & Feldman, 2015). In addition, the disease is always associated with an emotional and psychological impact, which can result in anxiety, reduced selfesteem, and depression or even thoughts of suicide (Tasoula et al., 2012). It affected more than 630 million people globally in 2015, thus being ranked as the eighth most common disease in the world (Disease, Injury, & Prevalence, 2016). Current research shows that several factors are involved in the development of this condition including an overgrowth of the skin commensal bacteria, obstruction of the follicle, excess production of sebum, and inflammation of the

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Section: R E T R a C T E Dmentioning

confidence: 99%

Retracted: Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with dual antibacterial and anti‐inflammatory action

Yang

Wang

et al. 2019

British J Pharmacology

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“…Such is the case, for instance, of rifampicin (Rif), a macrocyclic bactericidal antibiotic that is widely used in the treatment of infectious diseases, especially those caused by Mycobacterium, including tuberculosis and leprosy. Rif has been reported, for example, to attenuate cerebrospinal fluid (CSF) concentrations of inflammation markers as well as neuronal damage in children with bacterial meningitis [14]. Rif was also the first antibiotic reported to have therapeutic effects in chronic neurodegenerative conditions.…”

Section: Introductionmentioning

confidence: 99%

Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates

Acuña

Hamadat

Corbalán

et al. 2019

Cells

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: Aggregated forms of the synaptic protein α-synuclein (αS) have been proposed to operate as a molecular trigger for microglial inflammatory processes and neurodegeneration in Parkinson´s disease. Here, we used brain microglial cell cultures activated by fibrillary forms of recombinant human αS to assess the anti-inflammatory and neuroprotective activities of the antibiotic rifampicin (Rif) and its autoxidation product rifampicin quinone (RifQ). Pretreatments with Rif and RifQ reduced the secretion of prototypical inflammatory cytokines (TNF-, IL-6) and the burst of oxidative stress in microglial cells activated with αS fibrillary aggregates. Note, however, that RifQ was constantly more efficacious than its parent compound in reducing microglial activation. We also established that the suppressive effects of Rif and RifQ on cytokine release was probably due to inhibition of both PI3K- and non-PI3K-dependent signaling events. The control of oxidative stress appeared, however, essentially dependent on PI3K inhibition. Of interest, we also showed that RifQ was more efficient than Rif in protecting neuronal cells from toxic factors secreted by microglia activated by αS fibrils. Overall, data with RifQ are promising enough to justify further studies to confirm the potential of this compound as an anti-parkinsionian drug.

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“…So far, a variety of therapeutic agents have been demonstrated to reduce sebum production, inflammation, and bacterial counts (Becerro de Bengoa Vallejo, Losa Iglesias, Alou Cervera, Sevillano Fernandez, & Prieto Prieto, 2009;Inui, Aoshima, Ito, Kobuko, & Itami, 2012;Uppal, Singhi, Singhi, & Aggarwal, 2017). These chemicals are used either topically or systemically based on the severity of the acne lesion.…”

mentioning

confidence: 99%

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Yang

Wang

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

Background and Purpose Propionibacterium acnes is a Gram‐positive bacterium associated with the skin disorder acne. In this study, as fatty acids are considered to be important in the life habitat of P. acnes, we tested our lipopeptide library in an attempt to create potent P. acnes‐specific antimicrobial agents. Experimental Approach The antimicrobial activity of various lipopeptides was determined by measuring their minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore their mode of action. RAW264.7 cells stimulated with LPS and P. acnes respectively were used to measure their anti‐inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti‐inflammatory effects of the peptides tested in vivo. Key Results The most potent candidate, C16‐KWKW, was observed to be more active against P. acnes than against other non‐targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16‐KWKW was observed to be through interference with the integrity of the bacterial membrane, thereby impairing membrane permeability and causing leakage of inner contents of bacterial cells. Furthermore, C16‐KWKW inhibited the expression of pro‐inflammatory cytokines, such as IL‐1β, TNF‐α, and inducible NOS stimulated by both LPS and P. acnes, thus showing potential anti‐inflammatory activity, which was further verified in the in vivo animal studies. Conclusions and Implications C16‐KWKW is a lipopeptide displaying both anti‐P. acnes and anti‐inflammatory effects in vitro and in vivo and shows potential as a treatment for acne vulgaris induced by P. acnes.

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Role of Rifampin in Reducing Inflammation and Neuronal Damage in Childhood Bacterial Meningitis

Abstract: Pretreatment with single dose rifampin 30 minutes before ceftriaxone administration reduced the CSF concentrations of markers of inflammation and neuronal damage in children with bacterial meningitis.

Cited by 8 publications

References 14 publications

Retracted: Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with dual antibacterial and anti‐inflammatory action

Retracted: Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with dual antibacterial and anti‐inflammatory action

Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

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