Pharmacokinetic Study of Bioactive Glycopeptide from Strongylocentrotus droebachiensis After Intranasal Administration to Rats Using Biomarker Approach

Abstract

A glycopeptide fraction (GPF) from internal organs of green sea urchins (Strongylocentrotus droebachiensis Müller, Strongylocentrotidae) has been reported to be an effective bronchitis treatment. In this study, we evaluated the pharmacokinetic and tissue distribution of GPF, following single and repeated intranasal (i/n) administration over the course of seven days in rats. The method measuring lactate dehydrogenase as biomarker was used to analyse the plasma and tissue concentrations of GPF. GPF appears in the plasma 15 min after single i/n administration (100 µg/kg) and reaches its maximum at 45 min. The area under the curve (AUC)0–24 and Cmax were similar using both i/n and intravenous administration, while mean residence time (MRT) and T1/2 after i/n administration were significantly higher compared with intravenous (i/v) administration. The absolute bioavailability of GPF after i/n administration was 89%. The values of tissue availability (ft) provided evidence about the highest concentration of GPF in the nose mucosa (ft = 34.9), followed by spleen (ft = 4.1), adrenal glands (ft = 3.8), striated muscle (ft = 1.8), kidneys (ft = 0.5), and liver (ft = 0.3). After repeated dose administration, GPF exhibited significantly higher AUC0–24 and MRT, indicating its accumulation in the plasma.

Shotgun proteomics reveals putative polyesterases in the secretome of the rock-inhabiting fungus Knufia chersonesos

“…The protein digestion was performed following a standard enhanced, filter-aided sample preparation protocol (FASP) 52 with some modifications 53 . Briefly, twenty-micrograms protein were reduced using 20 mM dithiothreitol (37 °C, 30 min) and alkylated with 500 mM iodoacetamide (25 °C, 30 min), then filled up to 200 µl with 8 M urea in 50 mM Tris buffer and transferred into a Centrifugal Device (10 kDa cut-off, Merck Millipore).…”

“…The separated peptides were directly analysed in a high-resolution Q Exactive HF Orbitrap mass spectrometer (Thermo Fisher Scientific) for both identification and label-free quantification, according to Shikov et al 53 . Mass spectrometry full scans were performed in the ultrahigh-field Orbitrap mass analyser in the ranges 350-2000 m/z with a resolution of 60000, the maximum injection time (MIT) was 50 ms and the automatic gain control (AGC) was set to 3e 6 .…”

Cell-Free Coelomic Fluid Extracts of the Sea Urchin Arbacia lixula Impair Mitochondrial Potential and Cell Cycle Distribution and Stimulate Reactive Oxygen Species Production and Autophagic Activity in Triple-Negative MDA-MB231 Breast Cancer Cells

“…> 10 kDa promoting a prompt and strong MMP dissipation are surely present in the aqueous extract since this distinctive line is lost upon filtration. Moreover, it would be interesting to evaluate in vitro and in vivo the anti-inflammatory and pharmacokinetic properties of these molecules in mammalian models according to References [8,10] to contribute to the applicability of these compounds in the treatment of infections in humans.…”

“…Thus, identification of the water-soluble bioactive component(s) contained in the extracts deserve(s) further investigation aimed to devise novel promising prevention and/or treatment agents effective against highly malignant breast tumors.Further studies conducted by Björn et al [8] demonstrated that the synthetic peptides sequentially derived from the previously characterized centrocin 1 (CEN1 HC-Br and CEN1 HC) showed prominent microbicidal and anti-inflammatory activities on in vivo and in vitro mammalian models, representing an interesting resource for the treatment of infections in humans.Furthermore, a recent study by Katelnikova et al [9] highlighted that a glycopeptide fraction (GPF) derived from internal organs of the green sea urchins Strongylocentrotus droebachiensis possesses relevant anti-inflammatory effects, especially for the treatment of bronchitis. Moreover, the absorption and pharmacokinetics of GPF following single and repeated intranasal administration were evaluated over the course of seven days in rats [10].Another echinoderm species from which bioactive molecules were studied is Arbacia lixula, commonly found in the Mediterranean Sea and in the African Atlantic coast [11]. So far, the biomedical applications of molecules extracted from this marine invertebrate are very limited.…”

“…Furthermore, a recent study by Katelnikova et al [9] highlighted that a glycopeptide fraction (GPF) derived from internal organs of the green sea urchins Strongylocentrotus droebachiensis possesses relevant anti-inflammatory effects, especially for the treatment of bronchitis. Moreover, the absorption and pharmacokinetics of GPF following single and repeated intranasal administration were evaluated over the course of seven days in rats [10].…”