[The antagonistic action of epigallocatechin-3-gallate on microcystin LR-induced oxidative damage on hepatocytes of mice and the expression of cytochrome P450 2E1].
OBJECTIVE
To evaluate the effects of antagonistic action of epigallocatechin-3-gallate (EGCG) on microcystin LR (MC-LR) induced oxidative damage on mice and the expression of cytochrome P450 2E1 (CYP2E1) which was one of phase Iota detoxification enzymes.


METHODS
A total of 24 specific pathogen free (SPF) male BALB/c mice were randomly divided into four groups, including control group, MC-LR group, low concentration EGCG group, and high concentration EGCG group. Mice were sacrificed on the 15th day, body weight, and the relative organ weight, liver antioxidant enzyme level and lipid peroxidation product, liver histopathology and CYP2E1 gene and protein expression were detected and analyzed respectively.


RESULTS
(1) EGCG could antagonise the liver injury which had been damaged by MC-LR. (2) The malonaldehyde (MDA) level ((2.87 +/- 0.03) nmol/mg prot) and superoxide dismutase (SOD) level ((168.18 +/- 2.86) U/mg prot) in MC-LR group were significantly different when compared with the two EGCG treatment groups (the MDA values of the low and high concentration EGCG group were (2.37 +/- 0.05) nmol/mg prot and (1.44 +/- 0.05) nmol/mg prot, F = 906.63, P < 0.01; the SOD values were (176.55 +/- 2.98) U/mg prot and (184.89 +/- 1.53) U/mg prot, F = 32.32, P < 0.01). (3) MC-LR up-regulated the mRNA and protein expression of CYP2E1 (the mRNA values of MC-LR group and control were 1.41 +/- 0.26, 0.86 +/- 0.13, t = -4.22, P = 0.003; the protein values of MC-LR group and control were 0.24 +/- 0.03, 0.12 +/- 0.02, t = -9.21, P < 0.05). EGCG down-regulated the mRNA (the values of the low and high concentration EGCG group were 1.09 +/- 0.08, 0.99 +/- 0.09, F = 9.03, P = 0.004) and protein expression (the values of the low and high concentration EGCG group were 0.21 +/- 0.03, 0.14 +/- 0.02, F = 24.76, P < 0.05) of CYP2E1 which activated by MC-LR.


CONCLUSIONS
The up-regulation of CYP2E1 which induced by MC-LR was inhibited by EGCG intervention. EGCG might antagonize the oxidation damage of hepatocytes in a certain degree.
Han
Zhi-Xia
ZX
Department of Environmental Hygiene, School of Military Preventive Medicine, The Third Military Medical University, Chongqing 400038, China.
Yang
Lan
L
Zhang
Liang
L
Xu
Chuan
C
Shu
Wei-Qun
WQ
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008387:Marine Toxins; D051379:Mice; D008807:Mice, Inbred BALB C; D052998:Microcystins / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*
D008387:Marine Toxins; D052998:Microcystins; D002392:Catechin; C045651:epigallocatechin gallate; D019392:Cytochrome P-450 CYP2E1; C057862:cyanoginosin LR