Approbation of a Homologous Model of the Antitumor Vaccine Based on Mature Mouse Dendritic Cells to Study the Biodistribution of the Cell Product.

Homologous animal cell product was obtained in protocol developed for female BALB/c mice. Dendritic cell (DC) migration from the injection site into the draining lymph nodes was evaluated. The number of DC labeled with carboxyfluorescein succinimidyl ester (CFSE) in draining lymph nodes increased from 5.

Antigenotoxic Activity of Polyphenolic Composition BP-C2 in Mouse Germ Cells In Vivo.

In vivo antigenotoxic activity of BP-C2 composition (at doses of 60, 80, and 120 mg/kg) based on polyphenolic compounds derived from hydrolyzed lignin was evaluated in mouse germ cells. The BP-C2 composition dose-dependently reduced the aneugenic activity of topoisomerase II inhibitor etoposide in mouse oocytes without affecting the clastogenic activity of the genotoxicant. In mouse testicular cells, the BP-C2 composition reduced the DNA-damaging activity of the pro-oxidant genotoxicant dioxidine, but not etoposide.

Model of Accelerated Aging in CB6F2 Mice Induced by Ionizing Radiation.

A model for accelerated aging in mice was developed: CB6F2 mice aged 39-45 days were exposed to fractionated 4-fold relatively uniform γ-radiation (Cs, 0.98 Gy/min) at a total dose of 6.8 Gy.

Development of a Protocol for Obtaining a Homologous Cell Product of Animal Origin Intended for Preclinical Studies of Antitumor Vaccine CaTeVac.

When developing a program of preclinical studies of human cell-based drugs intended for adoptive immunotherapy of cancer patients, the biological effect should be substantiated by data describing their immunological action. Administration and study of human autologous dendritic cell vaccine to immunocompetent animals are not adequate in terms of immunological compatibility. It is possible to use immunocompromised, knockout, or transgenic animals or to obtain a homologous cellular product, namely, a preparation based on animal cells using a technology similar to obtaining the original preparation for clinical practice in humans.

Effect of Polyphenolic Composition BP-C2 on Lung Carcinogenesis Induced by Urethane in Progeny of Irradiated Male BALB/c Mice.

We studied the effects of polyphenolic composition BP-C2, comprising molybdenum with lignin derivatives, on lung carcinogenesis induced by urethane in the progeny of F male BALB/c mice preconceptionally exposed to radiation in a dose of 1 Gy. The multiplicity of lung tumors in the progeny of irradiated mice was higher than in the progeny of non-irradiated male parents by 50% in females and 43% in males (p<0.05).

[Polyphenols of natural origin against age-related disorders of tissue homeostasis.].

Aging-related disorders of tissue homeostasis may lead to excessive cell proliferation in the form of cancer and to extracellular matrix expansion in the form of fibroses. Death rates attributed to both of the conditions are decreased, according to epidemiological evidence, upon increased dietary intakes of polyphenols, including flavonoids, stilbenes, lignans, and curcuminoids. That is, polyphenols, although they have very different structures, unidirectionally influence the two opposite sides of balance in tissue homeostasis: the cells, which are able, and the extracellular matrix, which is unable to proliferate.

The Effect of Inactivating Heterozygous Mutation in NBS1 Gene on DNA Damage and Repair Markers and Apoptosis Markers in Mice.

We studied the state of the DNA repair system and apoptosis in young mice carrying heterozygous inactivating mutation in the NBS1 gene (c.1971insT, p.Arg658Stop).

Effects of Isoflavone-Rich NADES Extract of Roots and Astaxanthin-Rich Extract on Prostate Carcinogenesis in Rats.

Prostate cancer (PCa) is one of the most common male malignancies worldwide. In the current study, we evaluated the effects of a natural deep eutectic solvent (NADES) extract of roots rich in isoflavones (ISF) and extract rich in astaxanthin (ASX) on an -methyl--nitrosourea plus testosterone PCa model in rats. ISF consisted of puerarin, daidzein, genistein, formononetin and other polyphenols, while ASX contained lipids and unsaturated species in addition to astaxanthin.

Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning.

Chronic liver diseases affect more than 1 billion people worldwide and represent one of the main public health issues. Nonalcoholic fatty liver disease (NAFLD) accounts for the majority of mortal cases, while there is no currently approved therapeutics for its treatment. One of the prospective approaches to NAFLD therapy is to use a mixture of natural compounds.

Antigenotoxic and antimutagenic effects of lignin derivative BP-C2 against dioxidine and cyclophosphamide in vivo in murine cells.

The study investigated antigenotoxic and antimutagenic activity of novel lignin-derived polyphenolic composition (BP-C2) with ammonium molybdate towards cyclophosphamide and dioxidine in the bone marrow, blood and liver cells of BALB/c mice. BP-C2 was given to mice via gavage at 60, 80 and 120 mg/kg once 1 h before single intraperitoneal injection of a genotoxic agent. 1.

Assessment of antitumor activity of BP-C1, a platinum-based anticancer agent with a lignin-derived polymeric ligand, in autochthonous induced and spontaneous carcinogenesis rodent models.

Background: A standard approach to study the anticancer activity of novel drugs is their testing in animals with inoculated tumors, which has some limitations. An alternative is the use of spontaneous or carcinogen-induced tumor models as they have better translation potential. The carcinogen-induced and transgenic tumor models were used to assess the antitumor activity of BP-C1, a platinum-containing drug with lignin-derived polymeric ligand.

Astaxantin and Isoflavones Inhibit Benign Prostatic Hyperplasia in Rats by Reducing Oxidative Stress and Normalizing Ca/Mg Balance.

Benign prostatic hyperplasia (BPH) is a common pathology among aging men. Despite the broad pharmacological interventions, the available remedies to treat BPH are yet not devoid of side effects. Herbal compounds are suggested to be an alternative option for the BPH treatment.

A Use of Tritium-Labeled Peat Fulvic Acids and Polyphenolic Derivatives for Designing Pharmacokinetic Experiments on Mice.

Natural products (e.g., polyphenols) have been used as biologically active compounds for centuries.

Efficacy and Safety of Systemic and Locoregional Cisplatin Chronotherapy in Rats with Ovarian Carcinoma.

Aim: Alterations in circadian rhythms caused by tumor growth are thought to be clinically relevant as they affect the prognosis and treatment response. We aimed to evaluate the chronotherapeutic approach in rats with ovarian cancer receiving cisplatin intravenously (IV) or with hyperthermic intraperitoneal chemoperfusion (HIPEC) and to assess daily variations in tumor and intestinal epithelium proliferation.

Methods: In the pilot study, we used 12 intact rats and 12 rats with transplantable ovarian cancer, which were euthanized at ZT0 (08:00, lights on), ZT6, ZT12 and ZT18.

Modeling of Chemoperfusion vs. Intravenous Administration of Cisplatin in Wistar Rats: Adsorption and Tissue Distribution.

Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an established form of locoregional chemotherapy of peritoneum tumors. However, its efficacy and safety status remain a controversy, partially, due to scarce data on pharmacokinetics and toxicity profile of drugs under HIPEC. In the current study, 24 female Wistar rats were randomly assigned to receive cisplatin as HIPEC ( = 12, 20 mg/kg) or intravenously (i.

Evaluation of the genotoxic and antigenotoxic potential of lignin-derivative BP-C2 in the comet assay in vivo.

The genotoxic and antigenotoxic potential of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, was investigated as a radioprotector/radiomitigator for civil applications and as a medical countermeasure for radiation emergencies. Using the alkaline comet assay and methyl methanesulfonate (MMS, 40 mg/kg) as the DNA-damaging agent, these effects of BP-C2 on liver, bone marrow cells and blood leukocytes in rats were studied. The DNA damage was estimated by the DNA content in the comet tail (TDNA, %) 1, 6 and 18 h post exposure to MMS.

Exploring bioactivity potential of polyphenolic water-soluble lignin derivative.

Many natural substances exhibit anti-inflammatory activity and considerable potential in prophylaxis and treatment of allergies. Knowing exact molecular targets, which is required for developing these as medicinal products, is often challenging for multicomponent compositions. In the present study we examined novel polyphenolic substance, a water-soluble fraction of wood lignin (laboratory code BP-Cx-1).

Fourier transform ion cyclotron resonance mass spectrometry for the analysis of molecular composition and batch-to-batch consistency of plant-derived polyphenolic ligands developed for biomedical application.

Unlabelled: Complex plant-derived polyphenols are promising for biomedical application. Their high complexity prevents the use of conventional pharmacopoeia techniques to perform quality control. The goal of this study was to apply ultra-high-resolution mass spectrometry to evaluate the batch-to-batch consistency of the molecular composition of a polyphenolic ligand using appropriate statistical metrics.

Refinement of Compound Aromaticity in Complex Organic Mixtures by Stable Isotope Label Assisted Ultrahigh-Resolution Mass Spectrometry.

Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) provides a unique opportunity for molecular analysis of natural complex mixtures. In many geochemical and environmental studies structure-propertry relations are based solely on the elemental compositional information. Several calculated parameters were proposed to increase reliability of structural attribution, among which aromaticity indices (AI and AI) are widely used.

Photoreactivity of humic-like polyphenol material under irradiation with different wavelengths explored by FTICR MS and deuteromethylation.

The goal of this study was to establish reactivity of lignin-derived synthetic polyphenolic material under irradiation by ultraviolet (254 nm) and visible (460 and 525 nm) light in order to deeper examine relationships between the optical properties of this complex mixture and its individual constituents. In all photoirradiation experiments, blue shift of the fluorescence spectrum was observed. We aimed at understanding whether these changes could be explained on the basis of the chromophore interactions hypothesis, which implies destruction of electron-acceptor pairs via free radical transformations to be responsible for the alteration of optical properties.

[Comparative analysis of experimental data about the effects of various polyphenols on lifespan and aging.].

To analyze experimental data on the effect of various polyphenolic compounds on lifespan of mice, we approximated survival curves with the Gompertz model in its minimal form, which does not account for the heterogeneity of samples and the age-independent mortality. The plots of regressions of log0 (logarithm of the initial mortality) on  (the rate of aging) in series of control samples were used to assess the deviations of vectors directed from control to experimental data from the slopes of the control regressions. The analysis of published data suggests that resveratrol, polyphenol-containing grape skin extract, metformin, tocopherol, and the antioxidant SkQ1 do not produce changes beyond those possible upon comparing of different samples of a control population.

The Effect of Polyphenolic Composition BP-C3 on the Efficacy and Hematological Toxicity of Cyclophosphamide in the Chemotherapy of Mice Bearing Soft Tissue Sarcomas Induced by Benzo[a]pyrene.

This study aimed to evaluate the effect of lignin-derived polyphenolic composition BP-C3 on the efficacy and hematological toxicity of cyclophosphamide (CPA). Male and female Swiss-H derived mice bearing benzo[a]pyrene-induced soft tissue sarcomas were treated with CPA 300 mg/kg, BP-C3 75 mg/kg, or a combination. Tumor growth inhibition in male mice treated with CPA, BP-C3, or a combination of CPA and BP-C3 was significant and corresponded to 78%, 45%, and 82%, respectively, on day 21 after CPA administration on day 0.

Novel water-soluble lignin derivative BP-Cx-1: identification of components and screening of potential targets and .

Identification of molecular targets and mechanism of action is always a challenge, in particular - for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties.

Effect of the polyphenol composition BP-C3 on haematological and intestinal indicators of 5-fluorouracil toxicity in mice.

BP-C3 is a formulation, which comprises lignin-derived polyphenolic composition of benzenepolycarboxylic acids (BP-Cx-1) with iron complex, selenium, ascorbic acid and retinol, and possesses geroprotective activity. The present study examined the effect of BP-C3 (80 mg/kg, administered 18 times in total by gavage) on the development of haematological and intestinal manifestations of toxicity following 5-fluorouracil (5-FU; 150 mg/kg, administered once via intravenous injection) administration in outbred male Swiss-H Rappolovo (SHR) mice. The use of BP-C3 on therapeutic and preventative/therapeutic schedules demonstrated that it was protective against the toxic effect of 5-FU exerted on the lymphopoietic organs.

Radioprotective and radiomitigative effects of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, in two mouse strains exposed to total body irradiation.

Purpose: There remains an unmet medical need for radioprotective and mitigative agents. BP-C2 is a novel lignin-derived polyphenolic composition with ammonium molybdate, developed as radioprotector/radiomitigator.

Objectives: The present study evaluated BP-C2 for the mitigation of acute radiation syndrome (ARS).