Anethole Dithiolethione Increases Glutathione in Kidney by Inhibiting γ-Glutamyltranspeptidase: Biochemical Interpretation and Pharmacological Consequences

Joint Authors

Lucattelli, Monica
De Cunto, Giovanna
Giustarini, Daniela
Rossi, Ranieri
Dalle-Donne, Isabella
Galvagni, Federico
Bartolini, Desirée
Galli, Francesco
Milzani, Aldo
Santucci, Annalisa

Source

Oxidative Medicine and Cellular Longevity

Issue

Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-13, 13 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2020-09-28

Country of Publication

Egypt

No. of Pages

13

Main Subjects

Biology

Abstract EN

Aims.

Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia.

Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress.

Here, we investigated the molecular mechanisms behind these effects.

Results.

Oral treatment of rats confirmed the GSH enhancing properties of ADT; among the different organs examined in this study, only the kidney showed a significant GSH increase that was already observed at low-dose treatments.

The increase in GSH correlated with a decrease in γ-glutamyltranspeptidase (γ-GT) activity of the different tissues.

In vitro and ex vivo experiments with tubular renal cells and isolated perfused rat kidney showed that the cellular uptake of intact GSH was correlated with the extracellular concentrations of GSH.

Conclusions.

The prominent in vivopharmacological effect of ADT was a marked increase of GSH concentration in the kidney and a decrease of some systemic and renal biomarkers of oxidative stress.

In particular, by inhibition of γ-GT activity, it decreased the production cysteinylglycine, a thiol that has prooxidant effects as the consequence of its autooxidation.

The activity of ADT as GSH enhancer in both the circulation and the kidney was long-lasting.

All these characteristics make ADT a promising drug to protect the kidney, and in particular proximal tubule cells, from xenobiotic-induced damage.

American Psychological Association (APA)

Giustarini, Daniela& Galvagni, Federico& Dalle-Donne, Isabella& Milzani, Aldo& Lucattelli, Monica& De Cunto, Giovanna…[et al.]. 2020. Anethole Dithiolethione Increases Glutathione in Kidney by Inhibiting γ-Glutamyltranspeptidase: Biochemical Interpretation and Pharmacological Consequences. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1204289

Modern Language Association (MLA)

Giustarini, Daniela…[et al.]. Anethole Dithiolethione Increases Glutathione in Kidney by Inhibiting γ-Glutamyltranspeptidase: Biochemical Interpretation and Pharmacological Consequences. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-13.
https://search.emarefa.net/detail/BIM-1204289

American Medical Association (AMA)

Giustarini, Daniela& Galvagni, Federico& Dalle-Donne, Isabella& Milzani, Aldo& Lucattelli, Monica& De Cunto, Giovanna…[et al.]. Anethole Dithiolethione Increases Glutathione in Kidney by Inhibiting γ-Glutamyltranspeptidase: Biochemical Interpretation and Pharmacological Consequences. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1204289

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1204289