Modulation of human glutathione s-transferases by polyphenon e intervention.
OBJECTIVE
Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST).


METHODS
A total of 42 healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, a fasting blood sample was collected, and plasma and lymphocytes were isolated for assessment of GST activity and level. Following the baseline evaluation, study participants underwent 4 weeks of green tea polyphenol intervention in the form of a standardized Polyphenon E preparation at a dose that contains 800 mg epigallocatechin gallate (EGCG) once a day. Polyphenon E was taken on an empty stomach to optimize the oral bioavailability of EGCG. Upon completion of the intervention, samples were collected for postintervention GST assessment.


RESULTS
Four weeks of Polyphenon E intervention enhanced the GST activity in blood lymphocytes from 30.7 +/- 12.2 to 35.1 +/- 14.3 nmol/min/mg protein, P = 0.058. Analysis based on baseline activity showed that a statistically significant increase (80%, P = 0.004) in GST activity was observed in individuals with baseline activity in the lowest tertile, whereas a statistically significant decrease (20%, P = 0.02) in GST activity was observed in the highest tertile. In addition, Polyphenon E intervention significantly increased the GST-pi level in blood lymphocytes from 2,252.9 +/- 734.2 to 2,634.4 +/- 1,138.3 ng/mg protein, P = 0.035. Analysis based on baseline level showed that this increase was only significant (P = 0.003) in individuals with baseline level in the lowest tertile, with a mean increase of 80%. Repeated Polyphenon E administration had minimal effects on lymphocyte GST-mu and plasma GST-alpha levels. There was a small but statistically significant decrease (8%, P = 0.003) in plasma GST-alpha levels in the highest tertile.


CONCLUSIONS
We conclude that 4 weeks of Polyphenon E administration resulted in differential effects on GST activity and level based on baseline enzyme activity/level, with GST activity and GST-pi level increased significantly in individuals with low baseline enzyme activity/level. This suggests that green tea polyphenol intervention may enhance the detoxification of carcinogens in individuals with low baseline detoxification capacity.
Chow
H-H Sherry
HH
Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724, USA. schow@azcc.arizona.edu
Hakim
Iman A
IA
Vining
Donna R
DR
Crowell
James A
JA
Tome
Margaret E
ME
Ranger-Moore
James
J
Cordova
Catherine A
CA
Mikhael
Dalia M
DM
Briehl
Margaret M
MM
Alberts
David S
DS
D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D051549:Glutathione S-Transferase pi / Q000097:blood / Q000187:drug effects; D005982:Glutathione Transferase / Q000097:blood* / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000187:drug effects; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013662:Tea
D007527:Isoenzymes; D011480:Protease Inhibitors; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2; C119995:glutathione S-transferase alpha; C472086:polyphenon E