Renal Metabolism of Paracetamol: Studies in the Isolated Perfused Rat Kidney

Hart, S. J.; Calder, I. C.; Ross, Brian D.; Tange, J. D.

doi:10.1042/cs0580379

Cited by 16 publications

(5 citation statements)

References 11 publications

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“…Then, cleavage to thymol could be achieved by the activity of aryl sulfatases according to Munroe and Chang (). On the other hand, other way could be the cleavage to thymol by brush border enzymes (Hart, Calder, Ross, & Tange, ), before being reabsorbed. Moreover, a recent study in vitro on phenolic compounds suggests that glucuronidation, sulfation, and methylation may also occur in enterocytes (Contreras, Borrás‐Linares, Herranz‐López, Micol, & Segura‐Carretero, ).…”

Section: Resultsmentioning

confidence: 99%

Thymol, thyme, and other plant sources: Health and potential uses

Salehi

Mishra

Shukla

et al. 2018

Phytotherapy Research

397

243

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Thymol is a naturally occurring phenol monoterpene derivative of cymene and isomer of carvacrol. Thymol (10-64%) is one of the major constituent of essential oils of thyme (Thymus vulgaris L., Lamiaceae), a medicinal plant with several therapeutic properties. This plant, native to Mediterranean regions, is commonly used as a culinary herb and also with a long history of use for different medicinal purposes. Nowadays, thymol and thyme present a wide range of functional possibilities in pharmacy, food, and cosmetic industry. The interest in the formulation of pharmaceuticals, nutraceuticals, and cosmeceuticals based on thymol is due to several studies that have evaluated the potential therapeutic uses of this compound for the treatment of disorders affecting the respiratory, nervous, and cardiovascular systems. Moreover, this compound also exhibits antimicrobial, antioxidant, anticarcinogenesis, anti-inflammatory, and antispasmodic activities, as well as a potential as a growth enhancer and immunomodulator. In the present review, these bioactivities have been covered because some of them can contribute to explain the ethnopharmacology of thymol and its main source, T. vulgaris. Other important aspects about thymol are discussed: its toxicity and bioavailability, metabolism, and distribution in animals and humans.

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Section: Resultsmentioning

confidence: 99%

Thymol, thyme, and other plant sources: Health and potential uses

Salehi

Mishra

Shukla

et al. 2018

Phytotherapy Research

397

243

View full text Add to dashboard Cite

show abstract

“…32 On the other hand, it is conceivable that the cleavage to thymol is achieved by enzymes located at the luminal brush border. 33,34 Thus, thymol could be subsequently reabsorbed.…”

Section: Discussionmentioning

confidence: 99%

“…35,36 Extrahepatic glucuronidation was also proven for morphine 37 and for propofol, 35 which is structurally similar to thymol. In addition, renal glucuronidation of paracetamol, 34 1-naphtol, 38 and 4-dimethylaminophenol 39 was demonstrated by means of the isolated perfused rat kidney. Furthermore, variable activities of UDP-glucuronyltransferases were demonstrated for different tissues.…”

Section: Availability and Pharmacokinetics Of Thymolmentioning

confidence: 99%

Systemic Availability and Pharmacokinetics of Thymol in Humans

Kohlert¹,

Schindler

März

et al. 2002

The Journal of Clinical Pharma

143

104

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Essential oil compounds such as found in thyme extract are established for the therapy of chronic and acute bronchitis. Various pharmacodynamic activities for thyme extract and the essential thyme oil, respectively, have been demonstrated in vitro, but availability of these compounds in the respective target organs has not been proven. Thus, investigation of absorption, distribution, metabolism, and excretion are necessary to provide the link between in vitro effects and in vivo studies. To determine the systemic availability and the pharmacokinetics of thymol after oral application to humans, a clinical trial was carried out in 12 healthy volunteers. Each subject received a single dose of a Bronchipret TP tablet, which is equivalent to 1.08 mg thymol. No thymol could be detected in plasma or urine. However, the metabolites thymol sulfate and thymol glucuronide were found in urine and identified by LC-MS/MS. Plasma and urine samples were analyzed after enzymatic hydrolysis of the metabolites by headspace solid-phase microextraction prior to GC analysis and flame ionization detection. Thymol sulfate, but not thymol glucuronide, was detectable in plasma. Peak plasma concentrations were 93.1+/-24.5 ng ml(-1) and were reached after 2.0+/-0.8 hours. The mean terminal elimination half-life was 10.2 hours. Thymol sulfate was detectable up to 41 hours after administration. Urinary excretion could be followed over 24 hours. The amount of both thymol sulfate and glucuronide excreted in 24-hour urine was 16.2%+/-4.5% of the dose.

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“…Pang and Gillette (32) found no evidence for extrahepatic metabolism of acetaminophen in rats whose livers were excluded from the circulation. Acetaminophen is converted by rat kidney to the glucuronide (33), but studies indicate this conversion is quantitatively small and that this is also so in man (34,35). Two findings of ours support the view that the glucuronidation of the diflunisal took place primarily, if not completely, in liver and that the glucuronic acid moiety and glucose units of glycogen derived from the same pool of glucose-6-P.…”

Section: Discussionmentioning

confidence: 99%

Quantitation of the pathways of hepatic glycogen formation on ingesting a glucose load.

Magnusson

Chandramouli²,

Schumann³

et al. 1987

J. Clin. Invest.

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Diflunisal, 5-(2',4'-difluorophenyl)salicylic acid, excreted in urine as its glucuronide, was given to normal humans (n = 6) along with a glucose load specifically labeled with 14C. Glucuronide excreted by each subject was reduced to its glucoside and glucose from it degraded to yield the distribution of 14C in its six carbons. Randomization of the 14C from the specifically labeled glucose was taken as a measure of the extent to which glucose was deposited indirectly (i.e., glucose -) lactateglucose-6-P glycogen), rather than directly (i.e., glucose glucose-6-P glycogen). The maximum contribution to glycogen formation by the direct pathway was estimated to be 65±1%, on the assumption that glucuronide and glycogen are derived from the same hepatic pool of glucose-6-P in liver.Evidence that supports that assumption was obtained by comparing the randomization of 14C in the urinary glucuronide with that in glucose in blood from the hepatic vein of four of the subjects before and after they were given glucagon.

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Renal Metabolism of Paracetamol: Studies in the Isolated Perfused Rat Kidney

Cited by 16 publications

References 11 publications

Thymol, thyme, and other plant sources: Health and potential uses

Thymol, thyme, and other plant sources: Health and potential uses

Systemic Availability and Pharmacokinetics of Thymol in Humans

Quantitation of the pathways of hepatic glycogen formation on ingesting a glucose load.

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