The Effect of Radical Scavenger EPC-K1 and Methylprednisolone on Reactive Substances after Surgery

Toshihiro Hirai, Jun Hihara, Hideki Inoue, Tetsuya Toge, Yutaka Inoue^* and Takahiro Sakaue^*

Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University ^*Souyaku Research Institute, Senju Pharmaceutical Co. , Ltd.

Cytokine storms after surgical stress are reported to enhance tumor metastasis. Regulation of cytokine storms is extremely important in view of both organ failure control and cancer prognosis. We therefore studied the effect of the radical scavenger EPC-K1 and methylprednisolone (MP) on reactive substances IL-6, lipid peroxide (LPO), corticosterone, endotoxin (lipopolysaccharide, LPS), and nitric oxide (NO) in thoracolaparotomy (TL) in rats. EPC-K1 (5/mg/kg) or MP (50/mg/kg) was given intravenously 1 hour before surgery. Serum IL-6 and endotoxin were markedly elevated after TL. Serum LPO and corticosterone were elevated only immediately after TL. Increased serum IL-6 and endotoxin were suppressed by either EPC-K1 or MP. Serum LPO was suppressed by EPC-K1 but not by MP. Serum corticosterone was not suppressed by either EPC-K1 or MP. MP increased corticosterone. Lipopolysaccharide (0.5/mg/kg) given 1 hour after surgery markedly elevated serum IL-6 and NO and liver LPO. Neither EPC-K1 nor MP suppressed these substances sufficiently. In conclusion, EPC-K1 was more effective than MP in controlling postoperative reaction, but was not sufficient for protecting against a second attack.

Key words
operative stress, radical scavebger EPC-K1, methylprednisolone, cytokine, second attack

Reprint requests
Toshihiro Hirai Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553 JAPAN

Accepted
December 19, 2000

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