Effect of hesperetin, a citrus flavonoid, on bacterial enzymes and carcinogen-induced aberrant crypt foci in colon cancer rats: a dose-dependent study.
Hesperetin, an important bioactive compound in Chinese traditional medicine, has antioxidant and anticarcinogenic properties. Hesperetin is found in abundance in orange and grape juices (200-590 mg L(-1)) consumed in the daily diet. We have investigated the effect of different doses of hesperetin on faecal and colonic mucosal bacterial enzymes and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Wistar rats. The rats were divided into six groups and were fed a modified pellet diet for 16 weeks. Group 1 served as control and group 2 received the modified pellet diet along with hesperetin (30 mg kg(-1)). The rats in groups 3-6 rats were given a weekly subcutaneous injection of DMH (20 mg kg(-1)) for the first four weeks. Hesperetin was supplemented orally at different doses (10, 20 or 30 mg kg(-1)) for a total of 16 weeks. At the end of the experimental period all rats were killed. In DMH-treated rats, the activity of faecal and colonic mucosal bacterial enzymes, such as beta-glucuronidase, beta-galactosidase, beta-glucosidase, nitroreductase, sulfatase and mucinase, were significantly elevated, but in rats supplemented hesperetin along with DMH the activity was significantly lowered (P < 0.05). The total number of aberrant crypts was significantly increased in unsupplemented DMH-treated rats, while hesperetin supplementation to DMH-treated rats significantly reduced the total number of crypts. The results demonstrated that hesperetin supplementation at a dose of 20 mg kg(-1) played a potent role in suppressing the formation of aberrant crypt foci and reducing the activity of bacterial enzymes in colon cancer.
Aranganathan
Selvaraj
S
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608 002, Tamilnadu, India.
Selvam
Jayabal Panneer
JP
Nalini
Namasivayam
N
D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002957:Citrus / Q000737:chemistry; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005243:Feces / Q000201:enzymology / Q000382:microbiology; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006569:Hesperidin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008517:Phytotherapy; D011230:Precancerous Conditions / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D044950:Flavanones; D006569:Hesperidin; D019813:1,2-Dimethylhydrazine; C013015:hesperetin