Influences of dosage regimen and co-administration of low-molecular weight proteins and basic peptides on renal accumulation of arbekacin in mice

Murakami, Sachiko; Nagai, Junya; Fukui, Kenji; Yumoto, Ryoko; Takano, Mikihisa

doi:10.1093/jac/dkm512

Cited by 7 publications

(3 citation statements)

References 22 publications

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“…Because the average weight of used mouse is 27 g, and the average blood volume is 2 mL, the amount of lysozyme (0.57, 1.43, 2.86, or 5.72 μg per mouse) injected yielded a maximum concentration of 20, 50, 100, or 200 nM in the peripheral blood. Maximum amounts of used lysozyme (5.72 μg per mouse=212 μg/kg) administrated into mouse is safe because previous reports used up to 100 mg/kg [31], 300 mg/kg [32], or 1000 mg/kg [33]. To determine the molecular mechanism by which lysozyme inhibited the release of LPS-mediated HMGB1, we tested the effects of lysozyme on the transcriptional regulation of HMGB1 by LPS in HUVECs.…”

Section: Effect Of Lysozyme On Lps-and Clp-mediated Release Of Hmgb1mentioning

confidence: 99%

Anti-Inflammatory Effects of Lysozyme Against HMGB1 in Human Endothelial Cells and in Mice

Lee

et al. 2015

Inflammation

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High mobility group box 1 (HMGB1) was recently shown to be an important extracellular mediator of severe vascular inflammatory disease, sepsis. Lysozyme protects us from the ever-present danger of bacterial infection and binds to bacterial lipopolysaccharide (LPS) with a high affinity. Here, we show, for the first time, the anti-septic effects of lysozyme in HMGB1-mediated inflammatory responses in vitro and in vivo. The data showed that lysozyme posttreatment suppressed LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangement. Lysozyme also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in human endothelial cells. In addition, lysozyme inhibited the HMGB1-mediated activation of Akt, nuclear factor-κB (NF-κB), extracellular regulated kinases (ERK) 1/2 and production of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and chemoattractant protein-1 (MCP-1) in HUVECs. Furthermore, lysozyme reduced the cecal ligation and puncture (CLP)-induced release of HMGB1, migration of leukocytes, septic mortality, and pulmonary damage in mice. Collectively, these results suggest lysozyme as a candidate therapeutic agent for the treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

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Section: Effect Of Lysozyme On Lps-and Clp-mediated Release Of Hmgb1mentioning

confidence: 99%

Anti-Inflammatory Effects of Lysozyme Against HMGB1 in Human Endothelial Cells and in Mice

Lee

et al. 2015

Inflammation

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“…In a previous paper, we found that N-WASP181-200 had a 78-fold higher in vitro inhibitory potency for gentamicin binding to rat renal brush-border membrane than a low molecular weight protein, cytochrome c, when their IC 50 values were compared . However, the in vivo inhibitory potency of N-WASP181-200 was 16-fold as low as that of cytochrome c when their IC 50 values were compared . One of the main reasons for this disagreement between in vitro and in vivo studies was expected to be a poor delivery of N-WASP181-200 into the renal proximal tubule, where aminoglycosides are taken up.…”

Section: Discussionmentioning

confidence: 97%

“…On the other hand, under in vivo conditions, the inhibitory effect of N-WASP181-200 on renal accumulation of aminoglycosides was much weaker than was expected from the in vitro inhibitory effect; the 50% inhibitory concentration (IC 50 ) value of N-WASP181-200 for gentamicin binding to renal brushborder membrane in vitro (0.041 mM) was much lower than that of cytochrome c (3.20 mM) (15), while its IC 50 value for renal arbekacin accumulation in vivo (19.6 µmol/kg) was found to be higher than that of cytochrome c (1.23 µmol/kg) (16). We speculated that one of the main reasons for the apparent inconsistency between in vitro and in vivo studies may be the rapid degradation in the plasma and/or extensive binding to various tissues after intravenous injection of N-WASP181-200.…”

Section: Introductionmentioning

confidence: 97%

Effect of PEGylation of N-WASP181-200 on the Inhibitory Potency for Renal Aminoglycoside Accumulation

et al. 2009

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We previously showed that a 20-residue basic peptide, N-WASP181-200 (NISHTKEKKKGKAKKKRLTK), inhibits renal accumulation of aminoglycoside antibiotics such as gentamicin and arbekacin. The aim of this study is to determine whether PEGylation of N-WASP181-200 enhances its inhibitory potency for renal accumulation of aminoglycosides. N-terminally PEGylated peptide (PEG1k-N-W) was synthesized by conjugating N-WASP181-200 with PEG of approximately 1 kDa using the Fmoc protection/deprotection method. PEG1k-N-W decreased gentamicin binding to isolated rat renal brush-border membrane in a concentration-dependent manner, but the in vitro inhibitory potency of PEG1k-N-W was weaker than that of N-WAP181-200. On the other hand, under in vivo conditions, PEG1k-N-W decreased the renal accumulation of arbekacin more potently than N-WASP181-200. When injected intravenously, PEG1k-N-W showed a 1.7-fold longer plasma half-life relative to N-WASP181-200. In addition, the stability of N-WASP181-200 in renal brush-borer membrane suspension was found to be increased by PEGylation. Our findings suggest that PEGylation of N-WASP181-200 is a useful strategy for reducing dosage of the concomitant with which to decrease renal accumulation in the kidney, leading to prevention of aminoglycoside-induced nephrotoxicity.

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Cryptosporidium: Current State of Genomics and Systems Biological Research

Jex

Gasser

2013

Cryptosporidium: Parasite and Disease

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Influences of dosage regimen and co-administration of low-molecular weight proteins and basic peptides on renal accumulation of arbekacin in mice

Abstract: These data may be useful for prevention of arbekacin-induced nephrotoxicity owing to reduction of renal accumulation of the aminoglycoside.

Cited by 7 publications

References 22 publications

Anti-Inflammatory Effects of Lysozyme Against HMGB1 in Human Endothelial Cells and in Mice

Anti-Inflammatory Effects of Lysozyme Against HMGB1 in Human Endothelial Cells and in Mice

Effect of PEGylation of N-WASP181-200 on the Inhibitory Potency for Renal Aminoglycoside Accumulation

Cryptosporidium: Current State of Genomics and Systems Biological Research

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