Phaseolin, a Protein from the Seed of Phaseolus vulgaris, Has Antioxidant, Antigenotoxic, and Chemopreventive Properties

The present report was designed to determine the antioxidant and antigenotoxic effects of phaseolin (isolated from Phaseolus vulgaris) against mouse colon and liver damage induced by azoxymethane (AOM) and its colon chemopreventive effect. Eight groups with 12 mice each were utilized for an eight-week experiment: the control group was intragastrically (ig) administered 0.9% saline solution; the positive control group was intraperitoneally (ip) injected with 7.5 mg/kg AOM twice a week (weeks three and four of the experiment); three groups were ig administered each day with phaseolin (40, 200, and 400 mg/kg); and three groups were ig administered phaseolin daily (40, 200, and 400 mg/kg) plus 7.5 mg/kg AOM twice a week in weeks three and four of the experiment. The results showed that phaseolin did not produce oxidative stress, DNA damage, or aberrant crypts; in contrast, 100% inhibition of lipoperoxidation, protein oxidation, and nitrites induction generated by AOM was found in both organs, and DPPH radical capture occurred. The two highest phaseolin doses reduced DNA damage induced by AOM in both organs by more than 90% and reduced the AOM-induced aberrant crypts by 84%. Therefore, our study demonstrated the strong in vivo antioxidant, antigenotoxic, and chemopreventive potential of phaseolin.

PERSPECTIVES OF THE USE OF SULFORAPHANE IN ANIMAL MODEL OF COLORECTAL CARCINOGENESIS IN BRAZIL: A REVIEW

Colon cancer is a growing health problem in Brazil. According to data from the World Health Organization (WHO), colon cancer is among the top ten causes of mortality and morbidity in the world. Besides, the disease has a significant economic impact on the Brazilian public health system. Over the past five years, there has been an increased interest in use, isolation, characterization and determination of the biological actions of compounds such as broccoli. Experimental studies with genetically modified (GMOs) rats, mice, and rats using Sulforaphane have demonstrated their ability to prevent, delay and reverse pre-neoplastic lesions, improved survival, as well as acting on neoplastic cells with therapeutic action. Sulforaphane through activation of Nrf2 increases the activity of phase II enzymes such as glutathione S transferase (GST), which is involved in the elimination of xenobiotic compounds. Aberrant crypts are induced, in Wistar rats and mice, by genotoxic and non-genotoxic chemical compounds. Colon carcinogenesis is generally induced in rats and mice by two substances, 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM). Azoxymethane is often used concerning DMH because it is more potent and requires few reactions for its activation. It is possible to conclude that Sulforaphane, through its various biological actions, presents efficiency in the prevention of colon cancer and significant potential for use in future experimental studies with genetically modified rats, mice, and rats.

Chemopreventive Properties and Toxicity of Kelulut Honey inSprague DawleyRats Induced with Azoxymethane

Ethnopharmacological Relevance. Colon cancer has been a major problem worldwide. Kelulut honey (KH) is produced by the stingless bees fromTrigonaspecies and has strong antioxidant activities that could be one of the potential chemopreventive agents from natural resources.Aim of This Study. This study investigated the chemopreventive properties and toxicity of KH in Sprague Dawley rats induced with azoxymethane (AOM).Material and Method. Twenty-four male Sprague Dawley rats aged 5 weeks were divided into 4 groups: (G1) untreated group not induced with AOM, (G2) untreated group induced with AOM, (G3) treated group induced with AOM, and (G4) treated group not induced with AOM. Injection of AOM (15 mg/kg) was via intraperitoneal route once a week for two subsequent weeks. The treatment groups were given oral administration of KH (1183 mg/kg body weight) twice daily for 8 weeks.Results. Treatment with KH significantly reduced the total number of aberrant crypt foci (ACF) and aberrant crypts (AC) and crypt multiplicity. KH was not toxic to the animals since the level of blood profile parameters, liver enzymes, and kidney functions was in normal range.Conclusions. The current finding shows that KH has chemopreventive properties in rats induced with colorectal cancer and also was found not toxic towards the animals.

Evaluation of Blueberry Juice in Mouse Azoxymethane-Induced Aberrant Crypts and Oxidative Damage

Blueberry is a plant with a number of nutritional and biomedical capabilities. In the present study we initially evaluated the capacity of its juice (BJ) to inhibit the number of aberrant crypts (AC) induced with azoxymethane (AOM) in mouse. BJ was administered daily by the oral route to three groups of animals during four weeks (1.6, 4.1, and 15.0 μL/g), respectively, while AOM (10 mg/kg) was intraperitoneally injected to the mentioned groups, twice a week, in weeks two and three of the assay. We also included two control groups of mice, one administered distilled water and the other the high dose of BJ. A significant increase of AC was observed in the AOM treated animals, and a mean protection of 75.6% was determined with the two low doses of BJ tested; however, the high dose of the juice administered together with AOM increased the number of crypts more than four times the value observed in animals administered only AOM. Furthermore, we determined the antioxidant potential of BJ with anex vivoDPPH assay and found a dose-dependent decrease with a mean of 19.5%. We also determined the DNA oxidation/antioxidation by identifying 8-hydroxy-2′-deoxyguanosine adducts and found a mean decrease of 44.3% with the BJ administration with respect to the level induced by AOM. Our results show a complex differential effect of BJ related to the tested doses, opening the need to further evaluate a number of factors so as to determine the possibility of a cocarcinogenic potential.

Genistein, a soya isoflavone, prevents azoxymethane-induced up-regulation of WNT/β-catenin signalling and reduces colon pre-neoplasia in rats

The present study aimed to explore the role(s) of the soya isoflavone genistein (GEN) in preventing the development of colon pre-neoplasia, using Wingless/int (WNT)/β-catenin as a molecular marker of colon abnormality. Specifically, the effects on the WNT/β-catenin signalling pathway from GEN were examined by using an azoxymethane (AOM)-induced rat colon cancer model. Male Sprague–Dawley rats were fed a control (CTL), a soya protein isolate (SPI) or a GEN diet from gestation to 13 weeks of age. The first sampling was conducted at 7 weeks of age for pre-AOM analysis. The remaining rats were injected with AOM at 7 weeks of age. The descending colon was collected 6 weeks later for the evaluation of aberrant crypt foci (ACF), gene expression and nuclear protein accumulation. AOM injection induced aberrant nuclear accumulation of β-catenin in the CTL group but not in the SPI or GEN group. Moreover, the WNT target genesCyclin D1andc-Mycwere repressed by SPI and GEN. Meanwhile, SPI and GEN suppressed the expression of WNT signalling genes includingWnt5a,Sfrp1,Sfrp2andSfrp5to the similar level to that of the pre-AOM period. Rats fed SPI and GEN had a decreased number of total aberrant crypts. GEN feeding also resulted in a reduced number of ACF withN = 3 per foci. The reduction of WNT/β-catenin signalling was correlated with the decrease in total aberrant crypts. By testing WNT/β-catenin signalling as a biomarker of colon carcinogenic potential, we showed the novel role of GEN as a suppressor of carcinogen-induced WNT/β-catenin signalling in preventing the development of early colon neoplasia.