Equivocal Colonic Carcinogenicity of Aloe arborescens Miller var. natalensis Berger at High-Dose Level in a Wistar Hannover Rat 2-y Study

Authors

  • M. Yokohira,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • Y. Matsuda,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • S. Suzuki,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • K. Hosokawa,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • K. Yamakawa,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • N. Hashimoto,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • K. Saoo,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • K. Nabae,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • Y. Doi,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • T. Kuno,

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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  • K. Imaida

    1. Authors Yokohira, Matsuda, Suzuki, Hosokawa, Yamakawa, Hashimoto, Saoo, Kuno, and Imaida are with Onco-Pathology, Dept. of Pathology and Host-Defense, Faculty of Medicine, Kagawa Univ., 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Authors Nabae and Doi are with DIMS Inst. of Medical Science Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan. Direct inquiries to author Imaida (E-mail: imaida@med.kagawa-u.ac.jp).
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Abstract

ABSTRACT:  A 2-y carcinogenicity study of Aloe, Aloe arborescens Miller var. natalensis Berger, a food additive, was conducted for assessment of toxicity and carcinogenic potential in the diet at doses of 4% or 0.8% in groups of male and female Wistar Hannover rats. Both sexes receiving 4% showed diarrhea, with loss of body weight gain. The survival rate in the 4% female group was significantly increased compared with control females after 2 y. Hematological and biochemical examination showed increase of RBC, Hb, and Alb in the 4% males. The cause of these increases could conceivably have been dehydration through diarrhea. AST and Na were significantly decreased in the males receiving 4%, and Cl was significantly decreased in both 4% and 0.8% males. A/G was significantly increased in the 4% females, and Cl was significantly decreased (0.8%) in the female group. Histopathologically, both sexes receiving 4% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. Adenomas or adenocarcinomas in the cecum, colon, and rectum were observed in 4% males but not in the 0.8% and control male groups. Similarly, in females, adenomas in the colon were also observed in the 4% but not 0.8% and control groups. In conclusion, Aloe, used as a food additive, exerted equivocal carcinogenic potential at 4% high-dose level on colon in the 2-y carcinogenicity study in rats. Aloe is not carcinogenic at nontoxic-dose levels and that carcinogenic potential in at 4% high-dose level on colon is probably due to irritation of the intestinal tract by diarrhea.

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