Imidocarb, a potent anti-protozoan drug, up-regulates interleukin-10 production by murine macrophages

Katayama, Toyoko; Hayashi, Yasuhiko; Nagahira, Kazuhiro; Konishi, Kyoko; Yamaichi, Kozo; Oikawa, Shinzo

doi:10.1016/j.bbrc.2003.08.017

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…Some data point out its effect on the metabolism and/or utilization of polyamines . Besides the antiprotozoal action, the acetylcholinesterase inhibitory activity of IMD was also reported, , and it augmented the endogenous interleukin-10 production in mice . Furthermore, analysis of the nuclear fraction of cell lysates suggested the nucleic acid affinity of IMD, which is in line with the similar binding preference of related aromatic diamidine derivatives, including berenil, stilbamidine, and pentamidine. , Similar to DNA, the polyanionic glycosaminoglycans (GAGs) may be the potential targets of IMD, too.…”

Section: Introductionmentioning

confidence: 83%

Heparin and Heparan Sulfate Binding of the Antiparasitic Drug Imidocarb: Circular Dichroism Spectroscopy, Isothermal Titration Calorimetry, and Computational Studies

et al. 2018

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This study is aimed to assess the binding interaction between the antiparasitic cationic drug imidocarb (IMD) and sulfated glycosaminoglycans (GAGs), the ubiquitious nonprotein macromolecules of living organisms. These complex, heterogeneous polyanions are the integral constituents of cell membranes and the extracellular matrix and display affinity toward basic compounds, the binding of which may affect their biological functions. Exciton-type circular dichroism (CD) spectroscopic features measured at low salt concentration verify the heparin and heparan sulfate binding of IMD, which occurs in a cooperative manner by association of several drug molecules to a disaccharide unit. Isothermal titration calorimetry (ITC) measurements reassured the heparin interaction, resulting in a K value in the low micromolar range. In contrast, when considering high molar excess of the heparin-binding sites, closer resembling in vivo conditions, an entirely different CD signature was induced, suggesting a shift from the oligo- to monomeric binding mode. This observation was also supported by ITC measurements using an identical sample setup. To better mimic in vivo conditions, several measurements were performed in physiological salt concentration ranges. On the basis of these, the inter- and intramolecular origin of CD activity observed under low- and high-salt conditions refer to electrostatically held oligomeric and intermolecular H-bonded monomeric drug-GAG adducts, respectively. To complement the experimental data, quantum chemical calculations were performed to assess the photophysical and conformational properties of IMD, indicating the existence of nonlinear, nonplanar interconverting conformer populations. Such a structural flexibility may be important in the multiple, cooperative binding of IMD to sterically adjacent GAG sites.

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Section: Introductionmentioning

confidence: 83%

Heparin and Heparan Sulfate Binding of the Antiparasitic Drug Imidocarb: Circular Dichroism Spectroscopy, Isothermal Titration Calorimetry, and Computational Studies

et al. 2018

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“…Although genetic variables have been linked to carcinogenesis, the mechanism by which the IL-10 gene polymorphism causes cervical cancer is unknown. In vitro, IL-10 has been shown to have powerful immunosuppressive and antiinflammatory activities [35][36][37]. is cytokine is produced by a variety of cell types, such as CD4 T cells and monocytes/macrophages [38,39].…”

Section: Discussionmentioning

confidence: 99%

Association of the Interleukin-10-592C/A Polymorphism and Cervical Cancer Risk: A Meta-Analysis

et al. 2022

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A literature review showed some discrepancies regarding the association of -592C/A with the risk of cervical cancer. To allow more precise analysis of the data by increasing the number of cases studied and more acceptable generalization by considering results from different sources, the present meta-analysis was performed on available published studies that explored the relationship between SNP-592C/A of the IL-10 gene and the risk of cervical cancer. Eleven available studies, including 4187 cases and 3311 controls, were included in this study investigating the relationship between the -592C/A polymorphism of IL-10 and cervical cancer risk. Fixed-effects or random-effects models were performed with pooled odds ratios (ORs). Heterogeneity and bias tests were performed by the inconsistency test and funnel plot, respectively. The overall analysis showed an increased susceptibility to cervical cancer with the -592C/A polymorphism of the IL-10 gene for the recessive model (OR = 1.30, 95% CI = 1.14–1.49), dominant model (OR = 1.36, 95% CI = 1.09–1.70), and additive model (OR = 1.25, 95% CI = 1.09–1.44). Regarding ethnicity, a significant association of the -592C/A polymorphism of the IL-10 gene was linked to an elevated risk of cervical cancer for all genetic models (recessive, dominant, and additive) in the Asian populations and for the recessive and additive models in Caucasians with P < 0.05 . The -592C/A polymorphism of the IL-10 gene may be considered a risk factor for cervical cancer.

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“…, 1990). The fact that intraperitoneal administration of imidocarb markedly enhanced LPS‐induced IL‐10 production and inhibited LPS‐induced tumor necrosis factor (TNF)‐alpha production in mice suggests that imidocarb could lead to new therapeutic approaches in inflammatory conditions induced by protozoan infection (Katayama, 2003).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and bioavailability of imidocarb dipropionate in swine

Wang

et al. 2007

Vet Pharm & Therapeutics

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A two-way crossover study was performed in eight healthy young pigs to determine the pharmacokinetics of imidocarb dipropionate (IMDP) following intravenous (2 mg/kg b.w.) and intramuscular (2 mg/kg b.w.) administrations. Each animal received one intravenous and one intramuscular injection with a 30-day washout period between the two-treatments. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) assay with UV detector at regular intervals for up to 24 h post-injection. Intravenous plasma concentration profiles best fit a three-compartmental model yielding a mean system clearance (Cl((s))) of 558 mL/kg.h and a mean half-life of 13.91 h. Mean imidocarb AUC((0-infinity)) (microg.h/mL), V(c) (L/kg), V(d(area))(L/kg) and MRT((0-t)) (h) values were 3.58, 0.11, 14.36 and 1.46, respectively. Compartmental modeling of imidocarb, after intramuscular administration produced best fit for two-compartmental model yielding mean Kalpha (h(-1)), Cmax (microg/mL), tmax (h), and bioavailability (%) of 3.89, 2.02, 0.54, and 86.57 for the 2 mg/kg dose level. The present studies showed that IMDP was rapidly absorbed, widely distributed, and slowly eliminated. No adverse effects were observed in any of the pigs after i.v. and i.m. administrations of IMDP. The favorable PK behavior, such as the long half-life, acceptable bioavailability indicated that it is likely to be effective in pigs.

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Imidocarb, a potent anti-protozoan drug, up-regulates interleukin-10 production by murine macrophages

Cited by 8 publications

References 19 publications

Heparin and Heparan Sulfate Binding of the Antiparasitic Drug Imidocarb: Circular Dichroism Spectroscopy, Isothermal Titration Calorimetry, and Computational Studies

Heparin and Heparan Sulfate Binding of the Antiparasitic Drug Imidocarb: Circular Dichroism Spectroscopy, Isothermal Titration Calorimetry, and Computational Studies

Association of the Interleukin-10-592C/A Polymorphism and Cervical Cancer Risk: A Meta-Analysis

Pharmacokinetics and bioavailability of imidocarb dipropionate in swine

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