Long-term ingestion of reduced glutathione suppressed an accelerating effect of beef tallow diet on colon carcinogenesis in rats.
OBJECTIVE
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 beta-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 beta-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.
Shiraishi
Ryosuke
R
Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. ryosuke-shiraishi@nifty.com
Fujise
Takehiro
T
Kuroki
Tsukasa
T
Kakimoto
Takashi
T
Miao
Lujie
L
Sakata
Yasuhisa
Y
Tsunada
Seiji
S
Noda
Takahiro
T
Iwakiri
Ryuichi
R
Fujimoto
Kazuma
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001397:Azoxymethane / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000453:epidemiology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005223:Fats / Q000633:toxicity; D005978:Glutathione / Q000494:pharmacology*; D005980:Glutathione Reductase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011230:Precancerous Conditions / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051176:beta Catenin / Q000378:metabolism
D000975:Antioxidants; D005223:Fats; D051176:beta Catenin; D016718:Arachidonic Acid; C013698:tallow; D051546:Cyclooxygenase 2; D005980:Glutathione Reductase; D005978:Glutathione; D001397:Azoxymethane