A possible involvement of 3-monoglucuronyl-glycyrrhetinic acid, a metabolite of glycyrrhizin (GL), in GL-induced pseudoaldosteronism

Ohtake, Nobuhiro; Kido, Akiko; Kubota, Kunitsugu; Tsuchiya, Naho; Morita, Toshimi; Kase, Yoshio; Takeda, Susumu

doi:10.1016/j.lfs.2007.01.033

Cited by 36 publications

(29 citation statements)

References 27 publications

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“…GZ itself is poorly absorbed from the gastrointestinal tract in humans (Ploeger et al, 2001), rats (Sasaki et al, 2003;Gao et al, 2004), beagle dogs (Ren et al, 2010) and guinea pigs (Ohtake et al, 2007). GZ is hydrolysed to glycyrrhetic acid (GA) in the gastrointestinal tract by intestinal bacteria.…”

Section: Absorption Distribution Metabolism and Excretion Of Glycyrmentioning

confidence: 99%

“…GA is extensively absorbed in the gut and mostly glucuronidated in the liver to 3-mono-glucuronyl-glycyrrhetinic acid (3-MGA), but it is sulphated to a minor extent. In guinea pigs, the repeated administration of GZ (100 mg/kg per day for five consecutive days) caused the accumulation of 3-MGA in the plasma, but not of GA (Ohtake et al, 2007). The biliary excretion of 3-MGA provides a substrate for further hydrolysis by gut microflora, which leads to reabsorption of the resulting GA (Ploeger et al, 2001).…”

Section: Absorption Distribution Metabolism and Excretion Of Glycyrmentioning

confidence: 99%

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Scientific Opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30, miscellaneous substances) when used as a flavouring for all animal species

Högstrand¹

2015

EFSA Journal

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European Food Safety Authority (EFSA), Parma, Italy ABSTRACTGlycyrrhizic acid is extracted from the dried and ground rhizome and root portions of the perennial leguminous plant Glycyrrhiza glabra L., native to southern Europe and Central Asia, or other species of the genus Glycyrrhiza. It is currently listed in the register of flavouring substances, allowing its use in food without restriction. Glycyrrhyzic acid ammoniated is safe at the concentration of 1 mg/kg complete feed for all species, except chickens for fattening and laying hens. For these two categories, a safe concentration of 0.3 mg/kg complete feed applies. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) cannot conclude on the safety of the additive used in water for drinking. The FEEDAP Panel considers that the use of glycyrrhizic acid ammoniated in animal nutrition would not measurably increase consumer exposure. In the absence of data on user safety, the FEEDAP Panel considers it prudent to treat glycyrrhizic acid ammoniated as an irritant to skin, eyes and respiratory tract and as a skin sensitiser. The use of glycyrrhizic acid ammoniated in animal feeds would not pose a risk to the environment. As glycyrrhizic acid ammoniated is used in food as a flavouring, no further demonstration of efficacy is necessary. SUMMARYFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30-miscellaneous substances) when used as a flavouring for all animal species.The FEEDAP Panel concludes that glycyrrhyzic acid ammoniated is safe at the concentration of 1 mg/kg complete feed for all species except chickens for fattening and laying hens. For these two categories, a safe concentration of 0.3 mg/kg complete feed applies. The FEEDAP Panel cannot conclude on the safety of the additive used in water for drinking.The FEEDAP Panel considers that the use of glycyrrhizic acid ammoniated in animal nutrition would not measurably increase consumer exposure.In the absence of data on user safety, the FEEDAP Panel considers it prudent to treat glycyrrhizic acid ammoniated as an irritant to skin, eyes and respiratory tract and as a skin sensitiser.The use of glycyrrhizic acid ammoniated in animal feeds would not pose a risk to the environment.As glycyrrhizic acid ammoniated is used in food as a flavouring, no further demonstration of efficacy is necessary.Glycyrrhizic acid ammoniated for all animal species EFSA Journal 2015;13(1):3971 3

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Section: Absorption Distribution Metabolism and Excretion Of Glycyrmentioning

confidence: 99%

Section: Absorption Distribution Metabolism and Excretion Of Glycyrmentioning

confidence: 99%

Scientific Opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30, miscellaneous substances) when used as a flavouring for all animal species

Högstrand¹

2015

EFSA Journal

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“…This enzyme catalyzes the inactivation of cortisol to cortisone. Cortisol accumulates in the kidney and stimulates the aldosterone receptors in cells of the cortical collecting duct thus increasing Na + reabsorption [3,4,6]. Licoriceinduced pseudoaldosteronism also has been reported [7].…”

Section: Discussionmentioning

confidence: 99%

“…Licorice-induced hypokalemia usually has a mild progression. However, it may cause a critical failure in physical action by means of weakness followed by paralysis and may cause rhabdomyolysis, acute renal failure and hyperaldosteronism [3,4]. Generally, the onset and severity of the symptoms depend on the dose and duration of licorice intake, as well as individual susceptibility [5].…”

Section: Introductionmentioning

confidence: 99%

Acute renal failure after licorice ingestion: A case report

Veličković‐Radovanović¹,

Mitić²,

Kitić

et al. 2010

Open Medicine

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AbstractA 39-year-old female presented to the nephrology clinic emergency department with a complaint of muscle weakness and stomach pain. A detailed personal history revealed ingestion of 50–100 g herbal products which contained licorice, every day for 8 weeks to treat sterility. The herbal product was studied and determined to contain ‘licorice’ containing glycyrrhizic acid. Licorice (a plant which contains glycyrrhizic acid) induced hypokalemia which usually has a mild progression. However, it may cause critical failure in physical action by means of weakness followed by paralysis and may cause rhabdomyolysis, acute renal failure and hyperaldosteronism. This report presents the first case with acute renal failure due to licorice consumption from Serbia. In addition, the report aims to emphasize the importance of obtaining the detailed personal history of a patient for precise diagnosis.

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“…[12] Intriguingly, there are some reports that MGGA may cause pseudoaldosteronism for chronic hepatitis patients. [13,14] Therefore, the determination of MGGA is important for pharmaceutical quality in products. MGGA contents in products are shown in Table 4.…”

Section: -Monoglucuronyl-glycyrrhetinic Acid Concentration In Productsmentioning

confidence: 99%

Comparative study for pharmaceutical quality among bland-name drug and generic drugs of compound glycyrrhizin injections in China

Koga

Kikuchi

2012

J Basic Clin Pharma

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The physicochemical properties (pH and osmolarity), ingredients, and impurities containing in compound glycyrrhizin injections (eight items) marketed in China were compared with those in bland-name drug (Stronger Neo-Minophagen C injection). Glycyrrhizin (GZ), glycine (Gly), and -cysteine (CysH) as the ingredients, moreover, glycyrrhetinic acid (GA), 3-monoglucuronyl-glycyrrhetinic acid (MGGA), and -cystine (CysS) as the impurity were determined by HPLC. The pH and osmolarity were different every each pharmaceutical product, but the variation between batch was very small. On the other hand, although the contents of GZ, Gly, and CysH in bland-name drug were approximately 100% of the label claim, the contents of GZ in generic drugs were the range of 91.8-100.9%, indicating the GZ contents in four products were clearly less than value indicated in label (<97%). The remarkable difference was not accepted by impurities content such as GA and MGGA. The contents of CysH in generic drugs were the range of 79.9-100.4%, and CysS was determined in all generic drugs, suggesting that CysH may decompose to be CysS depending on the pH of injections in generic drug only. Because the variation of the ingredient content was big and products with a little quantity for the ingredients were recognized, establishment of the preparation that can maintain the prescribed ingredient content and the severity of the assay will be required.

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A possible involvement of 3-monoglucuronyl-glycyrrhetinic acid, a metabolite of glycyrrhizin (GL), in GL-induced pseudoaldosteronism

Cited by 36 publications

References 27 publications

Scientific Opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30, miscellaneous substances) when used as a flavouring for all animal species

Scientific Opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30, miscellaneous substances) when used as a flavouring for all animal species

Acute renal failure after licorice ingestion: A case report

Comparative study for pharmaceutical quality among bland-name drug and generic drugs of compound glycyrrhizin injections in China

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