All-trans-retinoyl beta-glucuronide: new procedure for chemical synthesis and its metabolism in vitamin A-deficient rats.
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ABSTRACT:
SUBMITTER: Becker B
PROVIDER: S-EPMC1217032 | biostudies-other | 1996 Feb
REPOSITORIES: biostudies-other
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Project description:All-trans-[11-3H]retinoyl beta-glucuronide (RAG) was synthesized in a single step from all-trans-[11-3H]retinoyl fluoride, with a 24% yield. After its intraperitoneal injection into rats, RAG was detected in the blood, liver, intestine and kidney during the following 24 h period. Although the concentration of radiolabelled metabolites decreased with time, RAG predominated at nearly all times in nearly all tissues. Small amounts of retinoic acid (RA) were also universally present, together with unidentified polar metabolites and small amounts of non-polar esters of RA. The major excretion products of RAG in faeces and urine were RA and polar metabolites. Thus RAG, although converted in part to RA in vivo, persists as a major component in blood and tissues for at least 24 h. These observations support the concept that the retinoid beta-glucuronides might serve a physiologically significant role in the function of vitamin A.
| S-EPMC1133443 | biostudies-other
Project description:All-trans-[11-3H]retinyl beta-glucuronide (all-trans-[11-3H]ROG) was synthesized from [3H]retinol by an improved synthetic procedure. After its intraperitoneal injection into rats, ROG is initially found as the predominant labelled component in the serum, but then is distributed to the liver, intestine, kidney and other organs of the body. Esters of vitamin A, which constituted the major metabolite of ROG, were detected in the liver as well as in other tissues. Of the labelled vitamin A esters derived from tritiated ROG in the liver and intestine, about 50% contained 5,6-epoxyretinol, which was characterized by its chromatographic behaviour, formation of an acetyl ester and lack of reactivity with diazomethane. Thus ROG, although converted to retinol in vivo, might also act physiologically in an intact form.
| S-EPMC1149161 | biostudies-other
Project description:All-trans-retinol reacts with methyl (2,3,4-tri-O-acetyl-1-bromo-1-deoxy-beta-D-glucopyran)uronate in the presence of Ag2CO3 to give the triacetate methyl ester of retinyl beta-glucuronide. Hydrolysis of this ester with sodium methylate in methanol gives retinyl beta-D-glucuronide in about 15% yield. The water-soluble retinyl beta-D-glucuronide was characterized by u.v.-visible, n.m.r. and mass spectra, by elemental analysis and by its susceptibility to hydrolysis by bacterial beta-glucuronidase. Retinyl beta-glucuronide, when administered intraperitoneally in saline (0.9% NaCl), supports well the growth of vitamin A-deficient rats.
| S-EPMC1147976 | biostudies-other
Project description:all-trans-beta-Retinoic acid is phosphorylated to retinoyl phosphate by bis(triethylamine) phosphate with yields of 10-15%. The product is soluble in methanol and is eluted from DEAE-cellulose acetate at a concentration of 0.1M-ammonium acetate in 99% (v/v) methanol. Its phosphate/retinoic acid molar ratio is 1. Retinoyl phosphate has an absorption maximum at 360nm in methanol, whereas retinoic acid has a maximum at 350 nm. The compound is hydrolysed at pH2 and pH13 for 20 min at 37 degrees C, but is relatively stable under the same conditions at pH4, 6, 8 and 10. Retinoyl phosphate (RF 0.1) can be separated from retinyl phosphate (RF 0.2) by chromatography on thin layers of silica gel in chloroform/methanol/water (60:25:4, by vol.).
| S-EPMC1164184 | biostudies-other
Project description:Soon after [11-3H]retinoic acid (RA) (1.1 x 10(8) d.p.m.) was administered orally to rats either as a large dose (115 micrograms = 0.38 mumol/rat) or mixed with unlabelled RA as a huge dose (22 mg = 73.33 mumol/rat), retinoyl beta-glucuronide (RAG) was identified and characterized as a significant metabolite in the serum and small intestine. Of the administered dose, 70% remained unchanged as retinoic acid in the stomach up to 1 h. Significant amounts of 5,6-epoxyretinoic acid, 4-hydroxyretinoic acid, esters of retinoic acid and several polar retinoids, including 4-oxoretinoic acid, were also detected in the stomach. No significant difference was observed in the nature of the retinoids found after a large or a huge dose; however, the ratio of RAG/RA was higher after a huge dose than after a large dose. Thus RAG, which is biologically active in vivo and in vitro, is formed quickly in significant amounts in tissues after a dose of RA.
| S-EPMC1151265 | biostudies-other
Project description:1. The effect of the administration of vitamin B(12) and biotin on the metabolic pattern of vitamin B(12) in biotin-deficient rats was studied. 2. No significant changes in the absorption and excretion of orally administered [(58)Co]vitamin B(12) were noted either in vitamin B(12)-treated and or in biotin-fed rats. A significant decrease of the uptake of orally given [(58)Co]vitamin B(12) was observed in the liver and kidneys of biotin-treated rats, whereas an increase of uptake in the kidneys of vitamin B(12)-treated rats was noted as compared with biotin-deficient animals. 3. No significant difference in the excretion of radioactivity was noted between biotin deficient and biotin-fed rats when [(58)Co]vitamin B(12) was administered by injection. A small decrease was observed in vitamin B(12)-treated rats. The retention of injected [(58)Co]vitamin B(12) by major organs of biotin-treated rats was lower than that of biotin-deficient rats. A lower content of [(58)Co]vitamin B(12) was also detected in the organs, with the exception of the kidneys, of vitamin B(12)-treated rats. 4. These results are discussed in terms of an interrelationship between biotin and vitamin B(12).
| S-EPMC1206903 | biostudies-other
Project description:(-)-Δ-9-tetrahydrocannabinol ((-)-Δ-9-THC) is the main psychoactive constituent in cannabis. During phase I metabolism, it is metabolized to (-)-11-hydroxy-Δ-9-tetrahydrocannabinol ((-)-11-OH-Δ-9-THC), which is psychoactive, and to (-)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol ((-)-Δ-9-THC-COOH), which is psychoinactive. It is glucuronidated during phase II metabolism. The biotransformation of (-)-Δ-9-tetrahydrocannabinol-glucuronide ((-)-Δ-9-THC-Glc) and (-)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol-glucuronide ((-)-Δ-9-THC-COOH-Glc) is well understood, which is mainly due to the availability of commercial reference standards. Since such a standardized reference is not yet available for (-)-11-hydroxy-Δ-9-tetrahydrocannabinol-glucuronide ((-)-11-OH-Δ-9-THC-Glc), its biotransformation is harder to study and the nature of the glucuronide bonding-alcoholic and/or phenolic-remains unclear. Consequently, the aim of this study was to investigate the biotransformation of (-)-11-OH-Δ-9-THC-Glc in vitro as well as in vivo and to identify the glucuronide by chemically synthesis of a reference standard. For in vitro analysis, pooled human S9 liver fraction was incubated with (-)-Δ-9-THC. Resulting metabolites were detected by high-performance liquid chromatography system coupled to a high-resolution mass spectrometer (HPLC-HRMS) with heated electrospray ionization (HESI) in positive and negative full scan mode. Five different chromatographic peaks of OH-Δ-9-THC-Glc have been detected in HESI positive and negative mode, respectively. The experiment set up according to Wen et al. indicates the two main metabolites being an alcoholic and a phenolic glucuronide metabolite. In vivo analysis of urine (n = 10) and serum (n = 10) samples from cannabis users confirmed these two main metabolites. Thus, OH-Δ-9-THC is glucuronidated at either the phenolic or the alcoholic hydroxy group. A double glucuronidation was not observed. The alcoholic (-)-11-OH-Δ-9-THC-Glc was successfully chemically synthesized and identified the main alcoholic glucuronide in vitro and in vivo. (-)-11-OH-Δ-9-THC-Glc is the first reference standard for direct identification and quantification. This enables future research to answer the question whether phenolic or alcoholic glucuronidation forms the predominant way of metabolism.
| S-EPMC7578173 | biostudies-literature
Project description:In humans, dehydroepiandrosterone and its sulfate ester metabolite DHEA-S are secreted predominantly from the adrenal cortex, and dehydroepiandrosterone is converted to steroid hormones, including androgens and estrogens, and neurosteroid. Dehydroepiandrosterone exerts protective effects against several pathological conditions. Although there are reports on the association between dehydroepiandrosterone and vitamins, the exact relationship between dehydroepiandrosterone and vitamin E remains to be determined. Therefore, we attempted to elucidate the effect of dehydroepiandrosterone on vitamin E status and the expression of various vitamin E-related proteins, including binding proteins, transporters, and cytochrome P450, in vitamin E-deficient rats. Plasma α-tocopherol levels in vitamin E-deficient rats increased in response to dehydroepiandrosterone administration. The expression of hepatic α-tocopherol transfer protein was repressed in vitamin E-deficient rats compared to that in control rats; however, dehydroepiandrosterone administration significantly upregulated this expression. Hepatic expression of CYP4F2, an α-tocopherol metabolizing enzyme, in vitamin E-deficient rats was decreased by dehydroepiandrosterone administration, whereas hepatic expression of ATP-binding cassette transporter A1, an α-tocopherol transporter, was not altered following dehydroepiandrosterone administration. Dehydroepiandrosterone repressed lipid peroxidation in the liver of vitamin E-deficient rats. Therefore, adequate dehydroepiandrosterone supplementation may improve lipid peroxidation under several pathological conditions, and dehydroepiandrosterone may modulate α-tocopherol levels through altered expression of vitamin E-related proteins.
| S-EPMC4865594 | biostudies-literature
Project description:In vitamin B-12 (cobalamin) deficiency the metabolism of propionyl-CoA and methylmalonyl-CoA are inhibited secondarily to decreased L-methylmalonyl-CoA mutase activity. Production of acylcarnitines provides a mechanism for removing acyl groups and liberating CoA under conditions of impaired acyl-CoA utilization. Carnitine metabolism was studied in the vitamin B-12-deficient rat to define the relationship between alterations in acylcarnitine generation and the development of methylmalonic aciduria. Urinary excretion of methylmalonic acid was increased 200-fold in vitamin B-12-deficient rats as compared with controls. Urinary acylcarnitine excretion was increased in the vitamin B-12-deficient animals by 70%. This increase in urinary acylcarnitine excretion correlated with the degree of metabolic impairment as measured by the urinary methylmalonic acid elimination. Urinary propionylcarnitine excretion averaged 11 nmol/day in control rats and 120 nmol/day in the vitamin B-12-deficient group. The fraction of total carnitine present as short-chain acylcarnitines in the plasma and liver of vitamin B-12-deficient rats was increased as compared with controls. When the rats were fasted for 48 h, relative or absolute increases were seen in the urine, plasma, liver and skeletal-muscle acylcarnitine content of the vitamin B-12-deficient rats as compared with controls. Thus vitamin B-12 deficiency was associated with a redistribution of carnitine towards acylcarnitines. Propionylcarnitine was a significant constituent of the acylcarnitine pool in the vitamin B-12-deficient animals. The changes in carnitine metabolism were consistent with the changes in CoA metabolism known to occur with vitamin B-12 deficiency. The vitamin B-12-deficient rat provides a model system for studying carnitine metabolism in the methylmalonic acidurias.
| S-EPMC1135203 | biostudies-other
Project description:BackgroundQuercetin (Qr), isoquercitrin (IQ), and quercetin-3-O-β-D-glucuronide (QG) are powerful phytochemicals that have been shown to exhibit disease prevention and health promotion properties. However, there may exist transformations between Qr, IQ, and QG in vivo. And the pharmacokinetic profiles of Qr, IQ, and QG have not been systematically compared. The pharmacokinetics study would be helpful to better understand the pharmacological actions of them.MethodsHerein, we developed a reliable HPLC-MS method to compare the pharmacokinetics of Qr, IQ, and QG after separate (50 mg/kg) oral administration of them in rats, using puerarin as internal standard. The detection was performed using negative selected ion monitoring. This method was validated in terms of selectivity, linearity, precision, accuracy, extraction recovery, matrix effect, and stability; and shows reliabilities in monitoring the pharmacokinetic behaviors of these three compounds.ResultsOur results showed that after separate oral administration of Qr, IQ, and QG, all of the compounds could be detected in plasma. In addition, QG could be detected in the Qr group; Qr and QG could be measured in the IQ group; and Qr could be found in rat plasma after 1.5 h of QG administration. Moreover, the AUC0-t of Qr in the; Qr group (2,590.5 ± 987.9 mg/L*min), IQ group (2,212.7 ± 914.1 mg/L*min), and QG group (3,505.7 ± 1,565.0 mg/L*min) was larger than the AUC0-t of QG in the; Qr group (1,550.0 ± 454.2 mg/L*min), IQ group (669.3 ± 188.3 mg/L*min), and QG group (962.7 ± 602.3 mg/L*min). The AUC0-t of IQ was the lowest among all groups.DiscussionQuercetin, IQ, and QG can all be absorbed into plasma. A mutual transformation exists between Qr and QG, and IQ can be metabolized into Qr and QG in SD rats. These results would provide a meaningful basis for understanding the pharmacological actions of these three compounds.
| S-EPMC6440464 | biostudies-literature