Glutathione antagonized cyclophosphamide- and acrolein-induced cytotoxicity of PC3 cells and immunosuppressive actions in mice.

Abstract

Aim: 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.

Conclusion: GSH exhibited protective effects against Cyc and Acr, but had no effect on the antitumor action of Cyc.