Distribution and excretion of3H-rhomotoxin in mice

Liu, Yongjia; Wang, Yazhen; Huan-yuan, Mao; Guo, Hao; Shu-mao, Liu; Cai, Yihua; Decun, Shen; Jiaxiu, Sun; Sun, Zhiwei

doi:10.1007/bf02911456

Cited by 2 publications

(2 citation statements)

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“…52.4% of the dose was excreted by 6 h via the urine and faeces. Approximately 60% was found bound to plasma proteins at 30 min (Liu et al, 1986). Dong et al (2014) determined rhodojaponins I, II and III 13 in the plasma of male Sprague-Dawley rats, following oral administration of 21 and 113 mg/kg bw extract of Rhododendri mollis flos containing 0.37% rhodojaponin I, 0.53% rhodojaponin II and 0.11% rhodojaponin III, respectively.…”

Section: 1mentioning

confidence: 99%

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Risks for human health related to the presence of grayanotoxins in certain honey

Schrenk¹,

Bignami²,

Bodin³

et al. 2023

EFS2

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The European Commission asked EFSA for a scientific opinion on the risks for human health of the presence of grayanotoxins (GTXs) in ‘certain honey’ from Ericaceae plants. The risk assessment included all structurally related grayananes occurring with GTXs in ‘certain’ honey. Oral exposure is associated with acute intoxication in humans. Acute symptoms affect the muscles, nervous and cardiovascular systems. These may lead to complete atrioventricular block, convulsions, mental confusion, agitation, syncope and respiratory depression. For acute effects, the CONTAM Panel derived a reference point (RP) of 15.3 μg/kg body weight for the sum of GTX I and III based on a BMDL 10 for reduced heart rate in rats. A similar relative potency was considered for GTX I. Without chronic toxicity studies, an RP for long‐term effects could not be derived. There is evidence for genotoxicity in mice exposed to GTX III or honey containing GTX I and III, showing increased levels of chromosomal damage. The mechanism of genotoxicity is unknown. Without representative occurrence data for the sum of GTX I and III and consumption data from Ericaceae honey, acute dietary exposure was estimated based on selected concentrations for GTX I and III reflecting concentrations measured in ‘certain’ honeys. Applying a margin of exposure (MOE) approach, the estimated MOEs raised health concerns for acute toxicity. The Panel calculated the highest concentrations for GTX I and III below which no acute effects would be expected following ‘certain honey’ consumption. The Panel is 75% or more certain that the calculated highest concentration of 0.05 mg for the sum of GTX I and III per kg honey is protective for all age groups regarding acute intoxications. This value does not consider other grayananes in ‘certain honey’ and does not cover the identified genotoxicity.

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Section: 1mentioning

confidence: 99%

“…52.4% of the dose was excreted by 6 h via the urine and faeces. Approximately 60% was found bound to plasma proteins at 30 min (Liu et al., 1986).…”

Section: Assessmentmentioning

confidence: 99%

Risks for human health related to the presence of grayanotoxins in certain honey

Schrenk¹,

Bignami²,

Bodin³

et al. 2023

EFS2

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Pharmacokinetics, bioavailability and tissue distribution studies of rhodojaponin III in mice using QTRAP LC–MS/MS

Zhang

Zhao

Yang

et al. 2019

Biomedical Chromatography

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Rhodojaponin III is a bioactive diterpenoid isolated from the medicinal plant Rhododendron molle G. Don. Quantitative analysis of rhodojaponin III was challenging and the pharmacokinetics of oral rhodojaponin III remained to be investigated. Here, a rapid and sensitive liquid chromatography tandem mass spectrometric (LC–MS/MS) method was developed and validated. The calibration curve was linear over the concentration range of 1–200 ng/mL (r = 0.992). The method was further validated following internationally approved guidelines and all the issues including intra‐ and inter‐day precision, accuracy, carryover, extraction recovery, matrix effects and stability met the recommended limits. The method was then applied to study the pharmacokinetics of rhodojaponin III in mice after intravenous (0.06 mg/kg) or oral (0.24 mg/kg) administration. The results showed that rhodojaponin III had fast oral absorption (time to peak concentration, 0.08 h) and good oral bioavailability (73.6%). In addition, rhodojaponin III was quickly eliminated after it was intravenously or orally administered, with half‐life values of 0.19 and 0.76 h, respectively. After oral administration, it was widely distributed in tissues including kidney, lung, heart, spleen and thymus, but had extremely low concentrations in liver and brain. The data presented in this study is beneficial for the further study of rhodojaponin III.

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Distribution and excretion of3H-rhomotoxin in mice

Cited by 2 publications

References 1 publication

Risks for human health related to the presence of grayanotoxins in certain honey

Risks for human health related to the presence of grayanotoxins in certain honey

Pharmacokinetics, bioavailability and tissue distribution studies of rhodojaponin III in mice using QTRAP LC–MS/MS

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