Biochemical indicators of hepatotoxicity in blood serum of rats under the effect

Kobylinska, Lesya

doi:10.15407/ubj87.02.122

Cited by 15 publications

(11 citation statements)

References 9 publications

(28 reference statements)

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“…In this study, even at the highest concentrations these PNCs (the dose equivalent to the amount of polymer used in a complex with the anticancer drug) had a very weak toxic effect on cell viability. The data of this investigation together with the results of studying general toxicity of the free PNC (Kobylinska et al 2015, 2016) suggest the biocompatibility of the PNC and confirm its potential for use as a drug delivery system (Heffeter et al 2013; Senkiv et al 2014).…”

Section: Discussionsupporting

confidence: 61%

“…Besides, if these groups were not stable, we would expect changes in the enzymatic activities in the experimental animals. However, we did not observe such changes in blood serum of the treated animals (Kobylinska et al 2015, 2016).…”

Section: Discussioncontrasting

confidence: 51%

“…In previous studies, we demonstrated an enhanced antineoplastic activity of the anticancer substances in mammalian tumor cells, when these substances were delivered by the developed PNC (Kobylinska et al 2015, 2016). In this study, even at the highest concentrations these PNCs (the dose equivalent to the amount of polymer used in a complex with the anticancer drug) had a very weak toxic effect on cell viability.…”

Section: Discussionmentioning

confidence: 96%

“…Previously, high efficiency of using PNCs has been demonstrated for delivery of doxorubicin (Senkiv et al 2014), ruthenium-containing antitumor preparation KP-1019 (Heffeter et al 2013), and experimental anticancer 4-thiazolidinone derivatives (Kobylinska et al 2015, 2016) to inhibit growth and survival of tumor cells in vitro and in tumor-bearing laboratory mice. The main goal of the present study was to estimate the indicators of general toxicity of the applied PNC in laboratory animals (rats and mice).…”

Section: Introductionmentioning

confidence: 99%

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Comb-like PEG-containing polymeric composition as low toxic drug nanocarrier

et al. 2018

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BackgroundDevelopment of biocompatible multifunctional polymeric drug carriers is crucial in modern pharmaceutics aimed to create “smart” drugs. The high potential of the PEGylated comb-like polymeric nanocarrier (PNC) in delivering both traditional and experimental drugs to tumor cells in vitro and in vivo has been demonstrated previously. In the present study, we investigated the general toxicity of polyethylene glycol (PEG) processed with both covalent and non-covalent attachments of PEG to compose a comb-like polymer that behaves like a simple chain of n monomers decorated with swollen side chains. The PNC possesses properties of a water-soluble surfactant containing methyl-terminated PEG side branches in some monomer units attached covalently to the carbon chain backbone.ResultsWe have demonstrated that the synthesized PNC possesses weak toxic effects toward human leukemia cells (HL-60 and Jurkat lines), as well as toward hepatocellular (HepG2), colon (HCT116) and breast (MCF-7) tumor cell lines. Additionally, after a long period (20 days) of intraperitoneal administration, the PNC had no significant toxic effects in laboratory white mice (470 mg/kg body mass in 1 ml) and Wistar rats (440 mg/kg body mass in 10 ml).ConclusionThe developed PNC we studied can be qualified as a compound of grade 4 toxicity (low toxicity substance). The reduced toxicity of this PNC in combination with its improved bioavailability and previously detected capability to enhance cytotoxicity toward tumor cells in vitro and potential tumor treatment effects in vivo suggests its potential as a safe drug delivery platform for treating various diseases, especially cancer.

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Section: Discussionsupporting

confidence: 61%

Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Comb-like PEG-containing polymeric composition as low toxic drug nanocarrier

et al. 2018

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“…Les-3833 was highly active towards the non-small-cell lung cancer cell line HOP-92 (GI 50 < 0.01 µM), colon cancer line HCT-116 (GI 50 = 0.018 µM), CNS cancer cell line SNB-75 (GI 50 = 0.0159 µM), ovarian cancer cell line OVCAR-3 (GI 50 = 0.0216 µM), and renal cancer cell line RXF 393 (GI 50 = 0.0197 µM) [18,21]. Les-3833 also demonstrated lower general toxicity in vivo compared with that of doxorubicin [10,[21][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Biodistribution and Anticancer Characteristics of Les-3833, A Novel 4-thiazolidinone-Based Lead Compound

et al. 2020

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Recently, we identified the promising anticancer potential of the synthetic 4-thiazolidinone-based anticancer lead compound Les-3833 which demonstrated tumor-suppressing action in vitro and in vivo. Based on the results of previous studies, the aim of this research was to investigate the cytotoxicity in vitro and the biodistribution in laboratory mice to support the biotherapeutic drug development of Les-3833. Les-3833 (2.5 mg/kg) was intravenously injected into male Balb/c mice. Measurements were performed at 5 min, 15 min, 1 h, 4 h, and 24 h time points in blood plasma, brain, liver, and kidney using high-performance liquid chromatography/tandem mass spectrometry. After the administration of Les-3833, the maximum level of this compound was observed in plasma at 2.08 min. In the brain, the mean maximum concentration of Les-3833 was 7.17 ng/mL at 5 min, while after 15 min, it was not found. In the liver, at 5 min, the maximum concentration was 1190 ng/g. At 15 min, concentration of Les-3833 in the liver decreased by 14.3%; at 6 h by 22.8%; and after 24 h by 64.7%. Its maximum concentration in kidney was 404 ng/g within 5–15 min, at 1 h it decreased by 36.1%, and after 24 h by 49.3%. Thus, Les-3833 was rapidly taken up by different organs from the bloodstream, partially metabolized in the liver, and excreted mainly through the kidneys, while in the brain, a very low concentration could be observed for only a short period of time.

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