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Long-term ingestion of reduced glutathione suppressed an accelerating effect of beef tallow diet on colon carcinogenesis in rats

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Abstract

Purpose

We have shown previously that long-term feeding of beef tallow increases colorectal cancer in rats. This study investigated the effects of enzymic antioxidant, reduced glutathione (GSH), on colon carcinogenesis in rats fed with beef tallow.

Methods

Colon carcinogenesis was induced by intraperitoneal injection of azoxymethane (AOM) to rats. Rats were fed with 10% beef tallow supplemented with or without 1% GSH in drinking water. Aberrant crypt foci (ACF) and expression of β-catenin in colonic mucosa were examined at 12 weeks. Cancers, related substances of oxidative stress and arachidonic acid cascade in plasma and normal colonic mucosa were determined at 44 weeks.

Results

GSH attenuated the number of ACF increased by beef tallow, but GSH had no influence on expression of β-catenin increased by AOM. Incidence of colon cancer was no different with or without GSH, but GSH attenuated the number of colon cancers in each rat. GSH suppressed plasma malondialdehyde concentration. GSH increased GSH concentration and activities of catalase, glutathione peroxidase and superoxide dismutase in colonic mucosa, and decreased cyclooxygenase-2, prostaglandin E2 and thromboxane B2 levels.

Conclusions

This study indicated that GSH suppressed the number of ACF, but the attenuation of colon carcinogenesis was limited to the number of colon cancers, although anti-oxidative effects and suppressive effects of arachidonic acid cascade were demonstrated by several indexes. These results suggested that colon carcinogenesis enhanced by beef tallow was partly caused by oxidative stress and arachidonic acid cascade, which were reduced by GSH.

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Abbreviations

ACF:

Aberrant crypt foci

AOM:

Azoxymethane

GSSG:

Glutathione disulfide

GSH:

Reduced glutathione

COX-2:

Cyclooxygenase-2

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Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (KAKEN) 20590728 (KF), 20790499 (TF) and 20590745 (RI).

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Authors and Affiliations

  1. Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Ryosuke Shiraishi, Takehiro Fujise, Tsukasa Kuroki, Takashi Kakimoto, Lujie Miao, Yasuhisa Sakata, Seiji Tsunada, Takahiro Noda, Ryuichi Iwakiri & Kazuma Fujimoto

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  1. Ryosuke Shiraishi
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  2. Takehiro Fujise
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  3. Tsukasa Kuroki
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Correspondence to Ryosuke Shiraishi.

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Shiraishi, R., Fujise, T., Kuroki, T. et al. Long-term ingestion of reduced glutathione suppressed an accelerating effect of beef tallow diet on colon carcinogenesis in rats. J Gastroenterol 44, 1026–1035 (2009). https://doi.org/10.1007/s00535-009-0101-3

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