Biodistribution and Pharmacokinetic Study of 3,3′ Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice

Gota, Vikram; Goda, Jayant Sastri; Doshi, Kartik; Patil, Anand; Sunderajan, Suvarna; Kumar, K. Vinod; Varne, Mahendra; Kunwar, Amit; Jain, Vimal K.; Priyadarshini, Indira

doi:10.1007/s13318-015-0301-6

Cited by 13 publications

(5 citation statements)

References 10 publications

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“…It is known that the pharmacokinetic profile and toxicity of some drugs are variable in different species [ 18 , 19 ]. The mouse was chosen as the animal model in this study because it is one of the most common species for evaluating drug preclinical efficacy [ 20 , 21 ], toxicology [ 22 ], biodistribution, and pharmacokinetics [ 23 – 25 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Bioavailability Study of Monocrotaline in Mouse Blood by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Chen

Zhang

Liu

et al. 2018

BioMed Research International

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Background and Aims The present study aimed to develop a simple and sensitive method for quantitative determination of monocrotaline (MCT) in mouse blood employing ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS) using rhynchophylline as an internal standard. Methods Proteins present in the blood samples were precipitated using acetonitrile. MCT was separated using a 1.7-μm ethylene bridged hybrid (BEH) C18 column (2.1 mm × 50 mm) with a gradient elution program and a constant flow rate of 0.4 mL/min. The LC mobile phase consisted of 10 mmol/L ammonium acetate (containing 0.1% formic acid) and acetonitrile. The total elution time was 4.0 min. The analytes were detected on a UPLC-ESI mass spectrometer in multiple reaction monitoring (MRM) mode and quantified. Results The new method for the determination of MCT has a satisfactory linear detection range of 1-2000 ng/mL and excellent linearity (r = 0.9971). The lower limit of quantification (LLOQ) of MCT is 1.0 ng/mL. Intra- and interassay precisions of MCT were ≤13% with an accuracy from 96.2% to 106.6%. The average recovery of the new method was >75.0%, and matrix effects were between 89.0% and 94.3%. Based on the pharmacokinetics data, the bioavailability of MCT in mice was 88.3% after oral administration. Conclusions The results suggest that the newly standardized method for quantitative determination of MCT in whole blood is fast, reliable, specific, sensitive, and suitable for pharmacokinetic studies of MCT after intravenous or intragastric administration.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Bioavailability Study of Monocrotaline in Mouse Blood by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Chen

Zhang

Liu

et al. 2018

BioMed Research International

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“…2,18 DSePA was also studied in detail for electron transfer reactions, GPx enzyme kinetic activity, cellular toxicity, in vitro and in vivo radioprotection and anti-cancer activity. 2,9,[18][19][20][21][22] At non-toxic doses, DSePA protected radiosensitive organs like hematopoietic system and gastrointestinal system from radiation induced damage. Oral administration of DSePA delayed the thoracic radiation (18 Gy) induced pneumonitis response in mice.…”

Section: Introductionmentioning

confidence: 99%

Unravelling the molecular interaction of diselenodipropionic acid (DSePA) with human serum albumin (HSA)

et al. 2022

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“…In mice oral administration is effective, contributing to potential improvement of patient compliance ( 85 ). The effects on normal tissue may be explained by the limited uptake of DSePA in tumors and the preferential accumulation in lung, intestine and kidney ( 86 ). Therefore, it is mainly investigated as co-therapy for cancer patients facing upper body radiotherapy.…”

Section: Protecting Normal Tissue During Radiotherapymentioning

confidence: 99%

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio

2021

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To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatment. These strategies, capable of either sensitizing or protecting tissues, target either tumor or normal tissue and are often focused on modulating of tissue oxygenation, hypoxia-inducible factor (HIF) stabilization, glucose metabolism, mitochondrial function and the redox balance. Several compounds or therapies are still in under (pre-)clinical development, while others are already used in clinical practice. Here, we describe different strategies from bench to bedside to optimize the therapeutic ratio through modulation of the cellular metabolism. This review gives an overview of the current state on development and the mechanism of action of modulators affecting cellular metabolism with the aim to improve the radiotherapy response on tumors or to protect the normal tissue and therefore contribute to an improved therapeutic ratio.

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Biodistribution and Pharmacokinetic Study of 3,3′ Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice

Abstract: DSePA has a favorable pharmacokinetic profile which makes it a potentially good candidate for further development as a radioprotective agent.

Cited by 13 publications

References 10 publications

Pharmacokinetics and Bioavailability Study of Monocrotaline in Mouse Blood by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Pharmacokinetics and Bioavailability Study of Monocrotaline in Mouse Blood by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Unravelling the molecular interaction of diselenodipropionic acid (DSePA) with human serum albumin (HSA)

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio

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