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

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]

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
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

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
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
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.
Campêlo LM, Gonçalves FC, Feitosa CM, de Freitas RM. PubMed PMID: 21639684
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.
Iersel ML, Ploemen JP, Struik I, van Amersfoort C, Keyzer AE, Schefferlie JG, van Bladeren PJ. PubMed PMID 8950226
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
37. Caffeine and uric acid mediate glutathione synthesis for neuroprotection.
Aoyama K, Matsumura N, Watabe M, Wang F, Kikuchi-Utsumi K, Nakaki T. PubMed PMID: 21371533
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