Bioavailability and pharmacokinetics of S-propargyl-L-cysteine, a novel cardioprotective agent, after single and multiple doses in Beagle dogs

Zheng, Yuanting; Xu, Jialin; Ma, Guoyi; Zhang, Jinlian; Zhu, Qing; Liu, Hongrui; Zhang, Peng; Zhu, Yi‐Zhun; Cai, Weimin

doi:10.3109/00498254.2011.617848

Cited by 8 publications

(3 citation statements)

References 10 publications

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“…A previous study indicated that H 2 S-releasing diclofenac derivatives, a novel class of non-steroidal anti-inflammatory drugs (NSAIDs), may be of clinical value in the treatment of osteolytic bone disease (35). In addition, preclinical studies have indicated that the novel hydrogen sulfide-modulating agent, S-propargyl-L-cysteine (SPRC) is a potent cardioprotective candidate (36). Our study provides a novel therapeutic role for H 2 S, which protects against HUVEC senescence.…”

Section: A B Cmentioning

confidence: 99%

Hydrogen sulfide prevents H2O2-induced senescence in human umbilical vein endothelial cells through SIRT1 activation

Suo

Zhao

Tang

et al. 2013

Molecular Medicine Reports

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The aim of the present study was to investigate the attenuation of endothelial cell senescence by H2S and to explore the mechanisms underlying the anti-aging effects of H2S. Senescence was induced in human umbilical vein endothelial cells (HUVECs) by incubation in 25 µmol/l H2O2 for 1 h. Senescence-associated β-galactosidase (SA-β-gal) activity was examined to determine the effects of H2S on senescent HUVECs. The results indicated that SA-β-gal activity in the H2O2-treated HUVECs was 11.2 ± 1.06%, which was attenuated in the NaHS group. Pretreatment with nicotinamide (NAM), a sirtuin 1 (SIRT1) inhibitor, inhibited the reduction in senescence associated with H2S. Immunoblot analyses revealed that SIRT1 levels in senescent HUVECs treated with NaHS (60 µM) were indistinguishable from controls; however, analyses of SIRT1 activity indicated that SIRT1 enzyme activity was enhanced. In addition, we found that H2S improves the function of senescent HUVECs. The present study demonstrated that H2S protects against HUVEC senescence, potentially through modulation of SIRT1 activity. Furthermore, this study establishes a novel endothelial protective effect of H2S.

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Section: A B Cmentioning

confidence: 99%

Hydrogen sulfide prevents H2O2-induced senescence in human umbilical vein endothelial cells through SIRT1 activation

Suo

Zhao

Tang

et al. 2013

Molecular Medicine Reports

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“…Pharmacokinetic study plays an important role in the early stage of the development of new drugs [ 11 ]. The failure of drug development is to a certain extent attributed to the poor pharmacokinetic properties, such as low bioavailability or low metabolic stability [ 12 ]. So far, some studies for pharmacokinetic profiles of several coumarins including oxypeucedanin after administration of the herb medicine ADR extract have been reported.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Pharmacokinetics and Bioavailability of Oxypeucedanin in Rats after Single Intravenous and Oral Administration

Zheng

Tang

et al. 2022

Molecules

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Oxypeucedanin, a furanocoumarin extracted from many traditional Chinese herbal medicines, has a variety of pharmacological effects. However, the independent pharmacokinetic characteristics and bioavailability of this compound remains elusive. In this study, a rapid, sensitive, and selective method using ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS) was developed for evaluating the intravenous and oral pharmacokinetics of oxypeucedanin. After intravenous administration of oxypeucedanin (2.5, 5, and 10 mg/kg), and intragastric administration of oxypeucedanin (20 mg/kg), blood samples were collected periodically from the tail vein. The plasma concentration-time curves were plotted, and the pharmacokinetic parameters were calculated using a non-compartmental model analysis. After intravenous administration of oxypeucedanin (single dosing at 2.5, 5, and 10 mg/kg) to rats, the pharmacokinetics fit the linear kinetics characteristics, which showed that some parameters including average elimination half-life (T1/2Z of 0.61~0.66 h), mean residence time (MRT of 0.62~0.80 h), apparent volume of distribution (VZ of 4.98~7.50 L/kg), and systemic clearance (CLZ of 5.64~8.55 L/kg/h) are dose-independent and the area under concentration-time curve (AUC) increased in a dose-proportional manner. Single oral administration of oxypeucedanin (20 mg/kg) showed poor and slow absorption with the mean time to reach the peak concentration (Tmax) of 3.38 h, MRT of 5.86 h, T1/2Z of 2.94 h, and a mean absolute bioavailability of 10.26% in rats. These results provide critical information for a better understanding of the pharmacological effect of oxypeucedanin, which will facilitate its research and development.

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“…Similar to SAC, SPRC serves as a substrate of CSE and increases endogenous H 2 S production. Compared with NaHS, SPRC is more chemically stable and releases H 2 S in a slower and more sustained manner, with a half-life of about 3 h in rats [ 17 ], and about 16 h in Beagle dogs [ 18 ]. As an H 2 S donor, SPRC elicits extensive regulation on pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

S-Propargyl-Cysteine, a Novel Hydrogen Sulfide Donor, Inhibits Inflammatory Hepcidin and Relieves Anemia of Inflammation by Inhibiting IL-6/STAT3 Pathway

Wang¹,

Tang²,

Hong³

et al. 2016

PLoS ONE

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Anemia of inflammation (AI) is clinically prevalent and greatly threatens public health. Traditional remedies have raised controversy during clinical practice, calling for alternative therapies. We have recently found that hydrogen sulfide (H2S) inhibits inflammatory hepcidin, the critical mediator of AI. However, due to the chemical property of H2S, there remains an urgent need for a stable H2S donor in AI treatment. Here we reported that S-propargyl-cysteine (SPRC), a novel water-soluble H2S donor, suppressed hepatic hepcidin and corrected hypoferremia induced by lipopolysaccharide. The effects of SPRC were reversed by inhibition of cystathionine γ-lyase, one of the major endogenous H2S synthases. Moreover, SPRC reduced serum hepcidin, improved transferrin saturation, and maintained erythrocyte membrane integrity in a chronic mouse AI model. Consistently, splenomegaly was ameliorated and splenic iron accumulation relieved. Mechanism study indicated that serum IL-6 content and hepatic Il-6 mRNA were decreased by SPRC, in parallel with reduced hepatic JAK2/STAT3 activation. On the whole, our data reveal the inhibition of inflammatory hepcidin by SPRC, and suggest SPRC as a potential remedy against AI.

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Bioavailability and pharmacokinetics of S-propargyl-L-cysteine, a novel cardioprotective agent, after single and multiple doses in Beagle dogs

Cited by 8 publications

References 10 publications

Hydrogen sulfide prevents H2O2-induced senescence in human umbilical vein endothelial cells through SIRT1 activation

Hydrogen sulfide prevents H2O2-induced senescence in human umbilical vein endothelial cells through SIRT1 activation

Preclinical Pharmacokinetics and Bioavailability of Oxypeucedanin in Rats after Single Intravenous and Oral Administration

S-Propargyl-Cysteine, a Novel Hydrogen Sulfide Donor, Inhibits Inflammatory Hepcidin and Relieves Anemia of Inflammation by Inhibiting IL-6/STAT3 Pathway

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