Glutathione

It's been shown that α1-adrenoceptor agonists (phenylpropanolamine, phenylephrine) deplete levels of glutathione. It's also been shown that α1-adrenoceptor antagonists (prazosin) help prevent depletion. Yohimbine, the selective α2-adrenoceptor antagonist has no effect.[20]

Glutathione Depleters

• Acetyl-L-carnitine¹[18]
• Aspartame (NutraSweet)[2][3]
• Chondroitin [21]
• Cinnamaldehyde² (in cinnamon oil)[29][30]
• Cinnamyl alcohol³[30]
• Crotonaldehyde⁴[32]
• Curcumin⁵[32]
• Diallyl disulphide (found in garlic essential oil)[14]
• (-)-Epigallocatechin-3-gallate (EGCG) [22]
• Ethacrynic acid⁶[32]
• Ethanol (edible alcohol)[34]
• Glucosamine[21]
• Lipoic Acid[35]
• Phenylephrine (m-synephrine, in bitter orange)⁷[19][17]
• Phenylpropanolamine[20]
• Prazosin[20]
• Strenuous exercise[15][16]

Dangerous Glutathione Depleters

Items in this section have been known to cause liver damage after they deplete glutathione levels. Compounds in this section should not be used with other compounds that deplete glutathione.

• Acetaminophen⁸[5][6]
• Acrolein[4]

Compounds that Induce Glutathione Or Prevent Depletion

• Black Tea (Camellia sinensis)[8]
• Caffeine[37]
• Capsaicin (in cayenne)[36]
• Chamomile recutita (German chamomile)[1]
• Crassostrea gigas extract[9]
• Ellagic acid[28]
• Fish oil[11]
• Garlic extract[7]
• Lemon essential oil[31]
• Linalool (in ho leaf and basil essential oils)[33]
• N-acetyl-cysteine
• Ocimum sanctum leaf extract[10]
• Prazosin[20]
• Rooibos[26][27]
• Silymarin (from Milk Thistle)[12][13]
• Thymoquinone (from Nigella sativa)[21]
• Vitamin B3 as nicotinic acid[24]
• Vitamin B3 as nicotinamide (niacinamide)[25]
• Vitamin B6 + Vitamin B9 (folic acid)[23]

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Chemical Properties

PubMed Compound ID: 124886
Molecular Weight: 307.32348 [g/mol]
Molecular Formula: C10H17N3O6S
XLogP3-AA: -4.5
H-Bond Donor: 6
H-Bond Acceptor: 8
IUPAC Name: (2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid
InChI: InChI=1S/C10H17N3O6S/c11-5(10(18)19)1-2-7(14)13-6(4-20)9(17)12-3-8(15)16/h5-6,20H,1-4,11H2,(H,12,17)(H,13,14)(H,15,16)(H,18,19)/t5-,6-/m0/s1
InChIKey: RWSXRVCMGQZWBV-WDSKDSINSA-N
Canonical SMILES: C(CC(=O)NC(CS)C(=O)NCC(=O)O)C(C(=O)O)N
Isomeric SMILES: C(CC(=O)N[CH](CS)C(=O)NCC(=O)O)[CH](C(=O)O)N

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Bibliography

1. Hepatoprotective Activity of Aqueous Ethanolic Extract of

Chamomile capitula in Paracetamol Intoxicated Albino Rats Ajay Kumar Gupta, Neelam Misra; American Journal of Pharmacology and Toxicology 1 (1): 17-20, 2006; ISSN 1557-4962

2. Effect of long term intake of aspartame on antioxidant defense status in liver.

Abhilash M, Paul MV, Varghese MV, Nair RH. PubMed PMID 21376768

3. Long-term consumption of aspartame and brain antioxidant defense status.

Abhilash M, Sauganth Paul MV, Varghese MV, Nair RH. PubMed PMID 22385158

4. Acrolein causes transcriptional induction of phase II genes by activation of Nrf2 in human lung type II epithelial (A549) cells.

Tirumalai R, Rajesh Kumar T, Mai KH, Biswal S. PubMed PMID 12084617

5. Therapeutic doses of acetaminophen stimulate the turnover of cysteine and glutathione in man.

Lauterburg BH, Mitchell JR. PubMed PMID 3584929

6.

Dose-dependent pharmacokinetics of acetaminophen: evidence of glutathione depletion in humans. Slattery JT, Wilson JM, Kalhorn TF, Nelson SD. PubMed PMID 3829578

7. The protective effects of garlic extract against acetaminophen-induced oxidative stress and glutathione depletion.

Anoush M, Eghbal MA, Fathiazad F, Hamzeiy H, Kouzehkonani NS. PubMed PMID 19806806

8. Role of glutathione in the antiulcer effect of hot water extract of black tea (Camellia sinensis).

Maity S, Vedasiromoni JR, Ganguly DK. PubMed PMID 9869262

9.

Impact of dietary supplement of Crassostrea gigas extract (JCOE) on glutathione levels and glutathione S-transferase activity in rat tissues. Gaté L, Schultz M, Walsh E, Dhalluin S, Nguyen Ba G, Tapiero H, Tew KD. PubMed PMID 9706474

10. Modulatory influence of alcoholic extract of Ocimum leaves on carcinogen-metabolizing enzyme activities and reduced glutathione levels in mouse.

Banerjee S, Prashar R, Kumar A, Rao AR. PubMed PMID 8710690

11. Possible role of glutathione in prevention of acetaminophen-induced hepatotoxicity enhanced by fish oil in male Wistar rats.

Kuralay F, Akarca US, Ozütemiz AO, Kutay F, Batur Y. PubMed PMID 9482353

12. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat.

Valenzuela A, Aspillaga M, Vial S, Guerra R. PubMed PMID 2813578

13. Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver.

Das SK, Vasudevan DM. PubMed PMID 17133738

14. Diallyl disulphide depletes glutathione in Candida albicans: oxidative stress-mediated cell death studied by two-photon microscopy.

Lemar KM, Aon MA, Cortassa S, O'Rourke B, Müller CT, Lloyd D. PubMed PMID 17534841

15. Training depletes muscle glutathione in patients with chronic obstructive pulmonary disease and low body mass index.

Rabinovich RA, Ardite E, Mayer AM, Polo MF, Vilaró J, Argilés JM, Roca J. PubMed PMID 16825756

16. Effects of endurance training and exercise on tissue antioxidative capacity and acetaminophen detoxification.

Lew H, Quintanilha A. PubMed PMID 1936063

17. Alpha-adrenergic modulation of glutathione metabolism in isolated rat hepatocytes.

Estrela JM, Gil F, Vila JM, Viña J. PubMed PMID 3202158

18. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity.

Hagen TM, Ingersoll RT, Wehr CM, Lykkesfeldt J, Vinarsky V, Bartholomew JC, Song MH, Ames BN. PubMed PMID 9689120

19. Structural isomerization of synephrine influences its uptake and ensuing glutathione depletion in rat-isolated cardiomyocytes.

Rossato LG, Costa VM, de Pinho PG, Carvalho F, de Lourdes Bastos M, Remião F. PubMed PMID 21140131

20. α1-Adrenoceptor antagonists prevent paracetamol-induced hepatotoxicity in mice

L E Randle, J G Sathish, N R Kitteringham, I Macdonald, D P Williams,1, and B K Park1 PubMed PMCID PMC2259197

21. The role of glucosamine, chondroitin and thymoquinone on the viability and proliferation of a HTB-93 rheumatoid arthritis cell model.

May M, Benghuzzi H, Tucci M, Mohamed A, Tan M, Norwood A. PubMed PMID 16817631

22. The effects of green tea (-)-epigallocatechin-3-gallate on reactive oxygen species in 3T3-L1 preadipocytes and adipocytes depend on the glutathione and 67 kDa laminin receptor pathways.

Wang CT, Chang HH, Hsiao CH, Lee MJ, Ku HC, Hu YJ, Kao YH. PubMed PMID 19065584

23. The effect of oral folic acid on glutathione, glycaemia and lipids in Type 2 diabetes.

Child DF, Hudson PR, Jones H, Davies GK, De P, Mukherjee S, Brain AM, Williams CP, Harvey JN. PubMed PMID 15244101

24. Dietary nicotinic acid supplementation improves hepatic zinc uptake and offers hepatoprotection against oxidative damage.

Tupe RS, Tupe SG, Agte VV. PubMed PMID 21262064

25. [The effect of nicotinamide on the activity of the glutathione- glutathione reductase system in subcellular fractions of regenerating rat liver].

[Article in Russian] Soroka VR, Skorobogataia TG, Skorobogatova ZM, Siverskiĭ GK. PubMed PMID 2531483

26. Effects of rooibos (Aspalathus linearis) on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease.

Marnewick JL, Rautenbach F, Venter I, Neethling H, Blackhurst DM, Wolmarans P, Macharia M. PubMed PMID 20833235

27. The effects of rooibos (Aspalathus linearis), green tea (Camellia sinensis) and commercial rooibos and green tea supplements on epididymal sperm in oxidative stress-induced rats.

Awoniyi DO, Aboua YG, Marnewick J, Brooks N. PubMed PMID 22228422

28. The effects of ellagic acid and vitamin E succinate on antioxidant enzymes activities and glutathione levels in different brain regions of rats after subchronic exposure to TCDD.

Hassoun EA, Vodhanel J, Holden B, Abushaban A. PubMed PMID 16455616

29. Effect of the food flavour cinnamaldehyde on the antioxidant status of rat kidney.

Gowder SJ, Devaraj H. PubMed PMID 17076691

30. Studies on trans-cinnamaldehyde II: Mechanisms of cytotoxicity in rat isolated hepatocytes.

Swales NJ, Caldwell J. PubMed PMID: 20650180

31. Antioxidant activity of Citrus limon essential oil in mouse hippocampus.

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32. Inhibition of glutathione S-transferase activity in human melanoma cells by alpha,beta-unsaturated carbonyl derivatives. Effects of acrolein, cinnamaldehyde, citral, crotonaldehyde, curcumin, ethacrynic acid, and trans-2-hexenal.

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33. Linalool decreases HepG2 viability by inhibiting mitochondrial complexes I and II, increasing reactive oxygen species and decreasing ATP and GSH levels.

Usta J, Kreydiyyeh S, Knio K, Barnabe P, Bou-Moughlabay Y, Dagher S. PubMed PMID 19428344

34. Ethanol lowers glutathione in rat liver and brain and inhibits methionine synthase in a cobalamin-dependent manner.

Waly MI, Kharbanda KK, Deth RC. PubMed PMID 21121936

35. Lipoic acid impairs glycine conjugation of benzoic acid and renal excretion of benzoylglycine.

Gregus Z, Fekete T, Halászi E, Klaassen CD. PubMed PMID: 8781786

36. Hypolipidemic and antioxidant effects of curcumin and capsaicin in high-fat-fed rats.

Manjunatha H, Srinivasan K. PubMed PMID: 17823620

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Footnotes

1. Acetyl-L-carnitine produced a 32% reduction in glutathione levels in old rat cells, and a 19% reduction in young rat cells in vitro.

2. Cinnamaldehyde can spontaneously react with glutathione without a catalyst. It's metabolites cinnamic acid and cinnamyl alcohol cannot. Of the three only cinnamic acid was found to have no effect on glutathione depletion.

3. Cinnamyl alcohol depletes glutathione but has a delayed action. It's theorized that cinnamyl alcohol only depletes glutathione after conversion into cinnamaldehyde by the action of alcohol dehydrogenase (ADH), which accounts for it's delayed action. This conclusion is based on the fact that cinnamaldehyde can spontaneously react with glutathione while cinnamyl alcohol cannot.

4. Approximately 50% GSH depletion was found after treatment with crotonaldehyde in vitro.

5. Approximately 50% GSH depletion was found after treatment with curcumin in vitro.

6. Approximately 50% GSH-depletion was found after treatment ethacrynic acid in vitro.

7. Test performed using both m-synephrine and p-synephrine found that only m-synephrine depletes glutathione levels.

8. Acetaminophen can cause liver damage when it depletes glutathione. It should not be taken with other compounds that reduce glutathione levels.