Advances in the pharmacological management of bacterial peritonitis

Pörner, Daniel; Vietinghoff, Sibylle von; Nattermann, Jacob; Strassburg, Christian P.; Lutz, Philipp

doi:10.1080/14656566.2021.1915288

Cited by 13 publications

(23 citation statements)

References 96 publications

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“…As a clinical challenge that often causes organ damage and death, LPS-induced peritonitis is associated with factors such as peritoneal dialysis, sepsis, and pathogenic microbial infections [ 2 , 3 , 4 ]. Although some encouraging progress has been achieved, its mechanism of action is still not fully elucidated [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

“…CYP1A1 attenuates LPS-induced mouse peritonitis via stimulating M2 macrophages [12]. (2) For the natural products, a series of molecules isolated from plants have shown anti-inflammatory activity in mouse models of LPS-caused peritonitis, including Ba-ME [13], Kaurenoid acid (KA) [14], Epimedium brevicornu Maxim ethanol extract (EBME) [15], and Ilexgenin A [5]. KA inhibits a series of index in LPS-induced peritonitis in mice, such as TNF-α, IL-33, and IL-1β [14].…”

Section: Introductionmentioning

confidence: 99%

“…An LPS-stimulated mouse peritonitis model was established. (2) Antiperitonitis activity of TLR4 inhibitor TAK 242. The effect of TAK 242 on the inflammatory cytokines in the peritoneal lavage fluid of mice was examined by the ELISA test.…”

Section: Introductionmentioning

confidence: 99%

“…Although a series of treatment progressions have been achieved, the mortality rate caused by peritonitis and its complications is still rising [ 1 ]. Based on the cause of its occurrence, peritonitis can be divided into aseptic peritonitis, bacterial peritonitis, peritoneal dialysis-related peritonitis, and LPS (lipopolysaccharide, LPS)-induced peritonitis [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…So far, the pathogenesis of LPS-mediated peritonitis has not been fully elucidated [ 1 , 2 ]. In the process of searching for clues to LPS-mediated peritonitis, transcriptomics may be an effective tool, which can be used to screen for promising candidate genes.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis

Liu

Zhang

Sun

et al. 2021

IJMS

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Peritonitis caused by LPS is a severe clinical challenge, which causes organ damage and death. However, the mechanism of LPS-induced peritonitis has not been fully revealed yet. Here, we investigated the transcriptome profile of the peritoneal tissue of LPS-induced peritonitis in mice. A model of LPS-induced peritonitis in mice was established (LPS 10 mg/kg, i.p.), and the influence of TAK 242 (TLR4 inhibitor) on the level of inflammatory cytokines in mouse peritoneal lavage fluid was investigated by using an ELISA test. Next, the peritoneal tissues of the three groups of mice (Control, LPS, and LPS+TAK 242) (n = 6) were isolated and subjected to RNA-seq, followed by a series of bioinformatics analyses, including differentially expressed genes (DEGs), enrichment pathway, protein-protein interaction, and transcription factor pathway. Then, qPCR verified-hub genes that may interact with TAK 242 were obtained. Subsequently, the three-dimensional structure of hub proteins was obtained by using homology modeling and molecular dynamics optimization (300 ns). Finally, the virtual docking between TAK 242 and hub proteins was analyzed. Our results showed that TAK 242 significantly inhibited the production of inflammatory cytokines in the peritoneal lavage fluid of mice with peritonitis, including IL-6, IFN-γ, IL-1β, NO, and TNF-α. Compared with the Control group, LPS treatment induced 4201 DEGs (2442 down-regulated DEGs and 1759 up-regulated DEGs). Compared with the LPS group, 30 DEGs were affected by TAK 242 (8 down-regulated DEGs and 22 up-regulated DEGs). A total of 10 TAK 242-triggered hub genes were obtained, and the possible docking modes between TAK 242 and hub proteins were acquired. Overall, our data demonstrated that a large number of DEGs were affected in LPS-triggered peritonitis mice. Moreover, the TLR4 inhibitor TAK 242 is capable of suppressing the inflammatory response of LPS-induced peritonitis. Our work provides clues for understanding the pathogenesis of LPS-induced peritonitis in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis

Liu

Zhang

Sun

et al. 2021

IJMS

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Diarylpentanoids, the privileged scaffolds in antimalarial and anti‐infectives drug discovery: A review

Ramli,

Mohd Faudzi

2023

Archiv der Pharmazie

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Asia is a hotspot for infectious diseases, including malaria, dengue fever, tuberculosis, and the pandemic COVID‐19. Emerging infectious diseases have taken a heavy toll on public health and the economy and have been recognized as a major cause of morbidity and mortality, particularly in Southeast Asia. Infectious disease control is a major challenge, but many surveillance systems and control strategies have been developed and implemented. These include vector control, combination therapies, vaccine development, and the development of new anti‐infectives. Numerous newly discovered agents with pharmacological anti‐infective potential are being actively and extensively studied for their bioactivity, toxicity, selectivity, and mode of action, but many molecules lose their efficacy over time due to resistance developments. These facts justify the great importance of the search for new, effective, and safe anti‐infectives. Diarylpentanoids, a curcumin derivative, have been developed as an alternative with better bioavailability and metabolism as a therapeutic agent. In this review, the mechanisms of action and potential targets of antimalarial drugs as well as the classes of antimalarial drugs are presented. The bioactivity of diarylpentanoids as a potential scaffold for a new class of anti‐infectives and their structure–activity relationships are also discussed in detail.

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Optimized Charge/Hydrophobicity Balance of Antimicrobial Peptides Against Polymicrobial Abdominal Infections

Du,

Yang,

Qin

et al. 2023

Macromolecular Bioscience

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Antimicrobial peptides (AMPs) potentially serve as ideal antimicrobial agents for the treatment of polymicrobial abdominal infections due to their broad‐spectrum antimicrobial activity and excellent biocompatibility. However, the balance of chain length, positive charges, and hydrophobicity on the antimicrobial activity of AMPs are still far from being optimal. Herein, a series of AMPs ([KX]n‐NH2, X = Ile, Leu or Phe, n = 3, 4, 5, or 6) with varied charges and hydrophobicity for the treatment of polymicrobial abdominal infections are designed. Specifically, [KI]4‐NH2peptide exhibits the best in vitro antimicrobial activity against Gram‐positive and ‐negative bacteria, as well as fungal strains. Based on the good cell biocompatibility, [KI]4‐NH2peptide is found to have negligible in vivo toxicity at the dosage of up to 28 mg kg−1. Furthermore, great in vivo therapeutic efficacy of [KI]4‐NH2peptide againstS. typhimuriumis demonstrated in the mice abdominal infection model. The design of short sequence of antimicrobial peptides with a charge/hydrophobicity balanced structures provides a simple and efficient strategy for potential clinical applications of antimicrobial peptide‐based biomaterials in a variety of bacterial infection diseases.

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Advances in the pharmacological management of bacterial peritonitis

Cited by 13 publications

References 96 publications

Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis

Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis

Diarylpentanoids, the privileged scaffolds in antimalarial and anti‐infectives drug discovery: A review

Optimized Charge/Hydrophobicity Balance of Antimicrobial Peptides Against Polymicrobial Abdominal Infections

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