Therapeutic effect of lecithinized superoxide dismutase Against colitis

Tomoaki Ishihara, Ken Ichiro Tanaka, Yuichi Tasaka, Takushi Namba, Jun Suzuki, Tsutomu Ishihara, Susumu Okamoto, Toshifumi Hibi, Mitsuko Takenaga, Rie Igarashi, Keizo Sato, Yutaka Mizushima, Tohru Mizushima

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Abstract

Ulcerative colitis (UC) involves intestinal mucosal damage induced by reactive oxygen species (ROS), in particular, super-oxide anion. Superoxide dismutase (SOD) catalyzes dismutation of superoxide anion to hydrogen peroxide, which is subsequently detoxified by catalase. Lecithinized SOD (PC-SOD) is a new modified form of SOD that has overcome previous clinical limitations of SOD. In this study, we examined the action of PC-SOD using an animal model of UC, dextran sulfate sodium (DSS)-induced colitis. DSS-induced colitis was amelio rated by daily intravenous administration of PC-SOD. Unmodified sOd produced a similar effect but only at more than 30 times the concentration of PC-SOD. In vivo electron spin resonance analysis confirmed that the increase in the colonic level of ROS associated with development of colitis was suppressed by PC-SOD administration. The dose-response profile of PC-SOD was bell-shaped, but simultaneous administration of catalase restored the ameliorative effect at high doses of PC-SOD. Accumulation of hydrogen peroxide was observed with the administration of high doses of PC-SOD, an effect that was suppressed by the simultaneous administration of catalase. We also found that either a weekly intravenous administration or daily oral administration of PC-SOD conferred protection. These results suggest that PC-SOD achieves its ameliorative effect against colitis through decreasing the colonic level of ROS and that its ineffectiveness at higher doses is because of the accumulation of hydrogen peroxide. Furthermore, we consider that intermittent or oral administration of PC-SOD can be applied clinically to improve the quality of life of UC patients.

Original languageEnglish
Pages (from-to)152-164
Number of pages13
JournalJournal of Pharmacology and Experimental Therapeutics
Volume328
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Ishihara, T., Tanaka, K. I., Tasaka, Y., Namba, T., Suzuki, J., Ishihara, T., Okamoto, S., Hibi, T., Takenaga, M., Igarashi, R., Sato, K., Mizushima, Y., & Mizushima, T. (2009). Therapeutic effect of lecithinized superoxide dismutase Against colitis. Journal of Pharmacology and Experimental Therapeutics, 328(1), 152-164. https://doi.org/10.1124/jpet.108.144451