doi:10.1016/j.taap.2006.01.001
Copyright © 2006 Elsevier Inc. All rights reserved.
Effect of dietary caraway (Carum carvi L.) on aberrant crypt foci development, fecal steroids, and intestinal alkaline phosphatase activities in 1,2-dimethylhydrazine-induced colon carcinogenesis
Muthaiyan Kamaleeswaria, Kumaraswami Deepthaa, Murugan Sengottuvelana and Namasivayam Nalini
, a, 
aDepartment of Biochemistry and Biotechnology, Annamalai University, Annamalainagar-608 002, Tamilnadu, India
Received 13 October 2005;
revised 3 December 2005;
accepted 3 January 2006.
Available online 17 February 2006.
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Abstract
Colon cancer is one of the most common malignancies in many regions of the world and is thought to arise from the accumulation of mutations in a single epithelial cell of the colon and rectum. Caraway (Carum carvi L. Umbelliferae) is a shrub with a long history as a medicinal plant since ancient times. The effect of different doses of caraway (CC) on the formation of aberrant crypt foci (ACF) and the levels of fecal bile acids, neutral sterols, and alkaline phosphatase (ALP) activities were studied in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. Animals were randomized into 6 groups. Group 1 served as control, and group 2 received 90 mg/kg body weight caraway orally everyday. Groups 3–6 rats were given subcutaneous injections of DMH (20 mg/kg body weight) once a week for the first 4 weeks to induce ACF. Rats in groups 4–6, in addition to DMH injections, received caraway at 30, 60, and 90 mg/kg body weight respectively p.o. everyday until the end of whole experimental period of 15 weeks. Caraway supplementation significantly reduced ACF development and also decreased the levels of fecal bile acids, neutral sterols, and tissue ALP activities. The histological alterations induced by DMH were also significantly improved. Overall, our results showed that all 3 doses of caraway inhibited tumorigenesis though the effect of the intermediary dose of 60 mg/kg body weight was more pronounced.
Keywords: Aberrant crypt foci; Bile acids; Caraway; Colon cancer; 1,2-Dimethylhydrazine
Abbreviations: ACF, aberrant crypt foci; ALP, alkaline phosphatase; b.w., body weight; CMC, carboxymethylcellulose; DMH, 1,2-dimethylhydrazine; H and E, hematoxylin and eosin; PBS, phosphate-buffered saline
Fig. 2. (A) Topographical view of normal crypt (20×). (B) Topographical view of ACF (arrows) with 6 crypts in whole-mount colon from a rat treated with DMH (40×). (C) Longitudinal sections of normal colon. Crypts are packed with thin lamina propria and regular patterns of epithelial linings (20×). (D) Histological changes in the colonic mucosa on DMH administration shows thickened mucosa with densely packed inflammatory cell infiltration and a higher degree of hyperplasia (10×). (E) Represents the carcinogen-induced colon with vascular congestion and vascular granulation (40×). (F) Represents 60 mg/kg b.w., caraway supplemented rat colon showing mucosal thickening in few areas and scattered or no infiltration of inflammatory cells in the mucosal layer (10×).
Fig. 3. (A) Effect of caraway on DMH-induced fecal bile acids excretion. Each value represents means ± SD of 12 animals. (a–d) P < 0.05 as compared with other groups. *P < 0.01 as compared to DMH group and other DMH+ caraway treatment groups. (B) Effect of caraway on DMH-induced fecal neutral sterol excretion. Each value represents means ± SD of 12 animals. (a, b) P < 0.05 as compared with other groups. *P < 0.01 as compared to DMH group and other DMH+ caraway treatment groups.
Fig. 4. Effect of caraway on DMH-induced alkaline phosphatase activity in rat feces. Each value represents means ± SD of 12 animals. Vertical lines above the bars represent SD of the means. (a, b) P < 0.05 as compared with other groups. *P < 0.01 as compared to DMH group and other DMH+ caraway treatment groups.
Table 1.
Composition of the diet

Table 2.
Aberrant crypt foci (ACF) formation in the colon of rats exposed to DMH and caraway

Each value represents means ± SD of 6 animals in each group.
a–cP < 0.05 as compared with other groups.
P < 0.01 as compared to DMH group and other DMH + caraway (CC) treatment groups.
Table 3.
Distribution of altered aberrant crypt foci (ACF) category in proximal, mid, and distal colon of rats exposed to DMH and caraway

Each value represents means ± SD of 6 animals.
a–cP < 0.05 as compared with other groups.