Glutathione antagonized cyclophosphamide- and acrolein-induced cytotoxicity of PC3 cells and immunosuppressive actions in mice.
OBJECTIVE
To study the antagonistic effect of glutathione (GSH) on toxicity of PC3 cell induced by cyclophosphamide (Cyc) and acrolein (Acr) and on immunosuppressive actions caused by Cyc.


METHODS
Splenocyte, PC3 cell proliferation and cell protein content were measured by tetrazolium (MTT) assay and Coomassie brilliant blue assay. Serum anti-SRBC hemolysin, agglutinin, and splenocyte proliferation were measured in normal and S-180-bearing mice. Tumors were weighed.


RESULTS
Pretreatment with GSH 2 mmol.L-1 reduced splenocyte proliferation inhibition from 18.64%, 49.72% to 6.78%, 18.36% (induced by Cyc 1, and 5 mmol.L-1), and PC3 cell proliferation inhibition from 27.7%, 45.3%, and 74.6% to 14.6%, 18.8%, and 49.1% (induced by Cyc 1, 3, and 5 mmol.L-1), and from 62.6%, 85.4%, and 90.6% to 41.9%, 57.7%, and 86.4% (induced by Acr 10, 25, and 50 mumol.L-1), respectively. In normal mice, s.c. GSH 75 or 150 mg.kg-1 b.i.d. x 5 d after i.p. Cyc 40 mg.kg-1, the hemolysin and the splenocyte proliferation were higher than those in normal mice i.p. Cyc 40 mg.kg-1 alone. Hemolysin, serum agglutinin, and splenocyte proliferation in S-180-bearing mice given s.c. GSH 150 mg.kg-1 b.i.d. x 10 d after i.p. Cyc 40 mg.kg-1 were also markedly higher than those in S-180-bearing mice given i.p. Cyc alone. But, according to tumor weight, GSH did not interfere the antitumor activity of Cyc in S-180-bearing mice.


CONCLUSIONS
GSH exhibited protective effects against Cyc and Acr, but had no effect on the antitumor action of Cyc.
Liu
X L
XL
Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou, China. liuxueli@yahoo.com
Chen
K
K
Ye
Y P
YP
Peng
X Y
XY
Qian
B C
BC
D000171:Acrolein / Q000009:adverse effects; D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000009:adverse effects*; D005978:Glutathione / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009363:Neoplasm Proteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology; D012510:Sarcoma 180 / Q000378:metabolism*; D013154:Spleen / Q000166:cytology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D018906:Antineoplastic Agents, Alkylating; D006460:Hemolysin Proteins; D009363:Neoplasm Proteins; D000171:Acrolein; D003520:Cyclophosphamide; D005978:Glutathione