Abstract
This work investigated the effects of Vitamin E (VE) on aberrant crypt foci (ACF) incidence, oxidative stress parameters (serum and hepatic VE concentration, and homocysteine, glutathione (GSH), and malondialdehyde (MDA) levels), and expression of both cyclooxygenase-2 (COX2) and proliferating cellular nuclear antigen (PCNA) in experimental colorectal carcinogenesis. Male Wistar rats received subcutaneous injections of 1,2-dimethylhydrazine (DMH) twice a week, for two weeks (40 mg/kg), except for the Control group. Animals were separated into groups that received different amounts of VE in the diet: 0 IU (0×), 75 IU (recommended daily intake, RDI), 225 IU (3× RDI), or 1500 IU (20× RDI), during (dDMH) or after (aDMH) administration of carcinogen. The 0×dDMH and 3×dDMH groups showed decreased serum VE levels. Hepatic VE concentration was higher in 3×aDMH as compared with the other groups. All the groups, except the Control and the 0×aDMH groups, had reduced GSH levels. The 0×dDMH, 0×aDMH, and 20×aDMH groups exhibited increased MDA levels. The aDMH groups had higher ACF incidence and PCNA expression. The 0×aDMH group presented higher ACF rate, followed by 20×aDMH. Moreover, the 3×aDMH group displayed reduced ACF incidence and COX2 expression. Multivariate analysis revealed that GSH modulated homocysteine levels and COX2. These results suggested that 1500 IU of VE is hazardous, whereas 225 IU of VE has beneficial effects on chemical colorectal carcinogenesis.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide
The 3×dDMH group did not display lower incidence of aberrant crypt foci (ACF), our findings suggested that 225 IU of Vitamin E (VE) might have an anti-initiation and/or anti-promotion role in chemical colorectal carcinogenesis
The multivariate statistical analysis showed that elevated hepatic GSH levels increased iCOX2 and decreased plasma homocysteine and hepatic MDA levels. These findings indicated that oxidative stress has an important role in chemical colorectal carcinogenesis—it interferes with early carcinogenesis biomarkers, like COX2, which reinforces the need to maintain oxidative balance
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide. It is estimated that over1.2 million new CRC cases emerged and 608,700 deaths occurred due to this condition in 2008.Australia, New Zealand, Europe, and North America have the highest incidence rates [1].Diet has been the most studied etiological factor in colorectal carcinogenesis and may account for approximately 50% of the attributable risk in countries with high susceptibility, such as the USA, England, and Australia [2].Vitamins and minerals have been suggested to influence the risk of developing CRC. Colorectal cancer (CRC) is the third most common cancer worldwide. 1.2 million new CRC cases emerged and 608,700 deaths occurred due to this condition in 2008. New Zealand, Europe, and North America have the highest incidence rates [1]. Diet has been the most studied etiological factor in colorectal carcinogenesis and may account for approximately 50% of the attributable risk in countries with high susceptibility, such as the USA, England, and Australia [2]. Vitamins and minerals have been suggested to influence the risk of developing CRC.
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