Synergistic interaction between excess caffeine and deficient iodine on the promotion of thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine.
Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan. Cancer Science
(Impact Factor: 3.52).
The combined effects of caffeine (1,3,7-trimethylxanthine) with iodine deficiency (ID) were examined in a rat two-stage thyroid carcinogenesis model using N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 6 groups each consisting of 10 animals, and received a single s.c. injection of 2800 mg/kg DHPN. From 1 week after the DHPN initiation, the rats were respectively fed a basal diet in which the protein was exchanged for 20% gluten, containing 1500 ppm caffeine + ID, 300 ppm caffeine + ID, 60 ppm caffeine + ID, 1500 ppm caffeine or ID or a basal diet alone for 12 weeks. Relative thyroid weights were significantly (P < 0.05) increased due to the development of proliferative lesions induced by the ID diet as compared to the DHPN-alone group value, which was enhanced by caffeine, albeit without statistical significance. Relative pituitary weights were significantly (P < 0.05) increased with 300 or 1500 ppm caffeine + ID as compared to the DHPN-alone group value. Serum thyroid stimulating hormone (TSH) levels were slightly increased by ID, an effect which was further enhanced by 300 or 1500 ppm caffeine. Serum thyroxine (T(4)) levels were slightly increased by caffeine or ID alone, but decreased by caffeine with ID. Histopathologically, thyroid follicular carcinomas were found only in the 1500 ppm caffeine + ID group, although thyroid follicular adenomas were detected in all the ID-treated groups. The multiplicity of focal thyroid follicular hyperplasias was significantly (P < 0.05) increased by 1500 ppm caffeine. These results indicate that caffeine may synergistically promote thyroid carcinogenesis with ID partially through a pituitary-dependent pathway in rats, implying the possible implication of routine caffeine intake in the promotion of thyroid carcinogenesis.
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- "The cotreatment with caffeine showed a tendency for elevating the serum TSH levels as compared to the respective noncaffeine group values. DISCUSSION Recently, we found that caffeine ingestion at high doses over 1,500 ppm dramatically increases the development of thyroid proliferative lesions in rats in combination with ID (Son et al., 2003). In the present study, it was clearly shown that caffeine intake interacts with ID but neither SDM nor PB to promote thyroid carcinogenesis. "
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ABSTRACT: The specificity of copromotion effects of caffeine with known goitrogenic factors on thyroid carcinogenesis was examined in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 8 groups, each consisting of 10 animals, and received a single sc injection of 2,800 mg/kg DHPN. From one week after the DHPN initiation, they were given basal diet, iodine deficiency (ID) diet, 500 ppm phenobarbital (PB) solution or 1,000 ppm sulfadimethoxine (SDM) solution with or without 1,500 ppm caffeine feeding for 12 weeks. The caffeine, PB, SDM, and ID treatments significantly (p < 0.05 or 0.01) increased the relative thyroid weights, and the increases with PB or ID were further (p < 0.05 or 0.01) enhanced in combination with caffeine. SDM drastically promoted thyroid carcinogenesis in association with increased serum TSH levels regardless of the caffeine treatment. Thyroid follicular carcinomas and adenomas were more frequently observed in the additional caffeine groups than in the ID alone groups. The incidence and multiplicity of focal thyroid follicular hyperplasias in the ID-treated groups were significantly (p < 0.05 and 0.01) elevated in the case of combination with caffeine. Increases in serum TSH levels with PB or ID were also further enhanced in combination with caffeine. Serum thyroid hormone levels were significantly (p < 0.01) decreased by SDM but significantly (p < 0.05 or 0.01) increased by caffeine, PB or ID. Our results clearly indicate that dietary caffeine at a high dose of 1,500 ppm interacts with ID, but neither SDM nor PB, to promote rat thyroid carcinogenesis although the combined caffeine + PB treatment somewhat affected thyroid weights as well as thyroid hormone levels.
Toxicologic Pathology 05/2004; 32(3):338-44. DOI:10.1080/01926230490431853 · 2.14 Impact Factor
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ABSTRACT: It is well known that obesity occurs in women with climacteric disorders. The aim of this study was to examine whether caffeine prevents obesity and bone loss in ovariectomized rats (ovx). Eight-week-old female Wistar rat were assigned to 4 groups: a sham-operated group fed the control diet (CE-2); an ovx-c group fed the control diet; an ovx-caf 0.15% group fed the control diet containing 1.5 g/kg of caffeine; and an ovx-caf 0.3% group fed the control diet containing 3 g/kg of caffeine. Body weights at 2-9 weeks and the final parametrail adipose tissue weights were significantly lower in the ovx-caf 0.3% group than in the ovx-c group. Food intakes were significantly lower in the ovx-caf 0.3% group than in the ovx-c group. After 9 weeks, the rats were killed and adipose tissues were sampled immediately. Basal lipolysis was increased in the ovx-caf 0.3% group fed the control diet containing 3 g/kg of caffeine than in the ovx-c group fed the control diet. The relative content of calcium (g/100 g body weight) in the ovx-caf 0.3% group was significantly increased compared with that in the ovx-c group. These results show a new possible role for caffeine in the prevention of lifestyle-related diseases.
Yakugaku zasshi journal of the Pharmaceutical Society of Japan 12/2004; 124(11):841-6. DOI:10.1248/yakushi.124.841 · 0.26 Impact Factor
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ABSTRACT: Green tea catechins (GTC), polyphenols extracted from the stalks and leaves of Camellia sinensis, are found in the different types of tea beverages and as antioxidant additives to many foods, snacks, fats and fatty oils. As a part of their safety assessment, subchronic toxicity was investigated in male and female F344 rats with dietary administration at concentrations of 0 (control), 0.3%, 1.25% and 5.0% for 90 days. The average daily intakes of GTC in each group were 180, 764 and 3525mg/kg body weight/day, respectively for males, and 189, 820 and 3542mg/kg body weight/day, respectively for females. No mortality or obvious clinical signs were observed throughout the experimental period but body weights were reduced from week 1 to the end of the experiment in 5.0% males. In serum biochemistry, alanine transaminase and alkaline phosphatase in 5.0% males and females and aspartate transaminase in 5.0% females were increased, together with the relative liver weights in both sexes receiving 5.0%. Although decreases were evident for total cholesterol in 0.3-5.0% males and triglycerides in 1.25% and 5.0% males and 5.0% females, these changes were not considered to be adverse. Hematology and histopathological observation revealed no GTC-related toxicological changes. Based on above findings, the no observed adverse effect level (NOAEL) of GTC was estimated to be 1.25% (764mg/kg body weight/day for males and 820mg/kg body weight/day for females).
Food and Chemical Toxicology 07/2008; 46(6):2224-9. DOI:10.1016/j.fct.2008.02.023 · 2.90 Impact Factor
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