It has been reported that some of the food additives may cause sensitization, inflammation of tissues, and potentially risk factors in the development of several chronic diseases. Thus, we hypothesized that expressions of common inflammatory molecules -known to be involved in the development of various inflammatory conditions and cancers -are affected by these food additives. We investigated the effects of commonly used food preservatives and artificial food colorants based on the expressions of NFκB, GADD45α, and MAPK8 (JNK1) from the tissues of liver. RNA was isolated based on Trizol protocol and the activation levels were compared between the treated and the control groups. Tartrazine alone could elicit effects on the expressions of NFκB (p = 0.013) and MAPK8 (p = 0.022). Azorubine also resulted in apoptosis according to MAPK8 expression (p = 0.009). Preservatives were anti-apoptotic in high dose. Sodium benzoate (from low to high doses) dose-dependently silenced MAPK8 expression (p = 0.004 to p = 0.002). Addition of the two preservatives together elicited significantly greater expression of MAPK8 at half-fold dose (p = 0.002) and at fivefold dose (p = 0.008). This study suggests that some of the food preservatives and colorants can contribute to the activation of inflammatory pathways.
The intake of carcinogenic and chemopreventive compounds are important nutritional factors related to the development of malignant tumorous diseases. Repetitive long interspersed element-1 (LINE-1) DNA methylation pattern plays a key role in both carcinogenesis and chemoprevention. In our present in vivo animal model, we examined LINE-1 DNA methylation pattern as potential biomarker in the liver, spleen and kidney of mice consuming green tea (Camellia sinensis) extract (catechins 80%), a chinese bayberry (Morella rubra) extract (myricetin 80%), a flavonoid extract (with added resveratrol) and coffee (Coffee arabica) extract. In the organs examined, carcinogen 7,12-dimethylbenz(a)anthracene (DMBA)-induced hypomethylation was prevented by all test materials except chinese bayberry extract in the kidneys. Moreover, the flavonoid extract caused significant hypermethylation in the liver compared to untreated controls and to other test materials. The tested chemopreventive substances have antioxidant, anti-inflammatory properties and regulate molecular biological signaling pathways. They increase glutathione levels, induce antioxidant enzymes, which decrease free radical damage caused by DMBA, and ultimately, they are able to increase the activity of DNA methyltransferase enzymes. Furthermore, flavonoids in the liver may inhibit the procarcinogen to carcinogen activation of DMBA through the inhibition of CYP1A1 enzyme. At the same time, paradoxically, myricetin can act as a prooxidant as a result of free radical damage, which can explain that it did not prevent hypomethylation in the kidneys. Our results demonstrated that LINE-1 DNA methylation pattern is a useful potential biomarker for detecting and monitoring carcinogenic and chemopreventive effects of dietary compounds.
Both the intake of beneficial olive oil and of harmful trans-fatty acids (TFAs) in consumed foods are of great significance in tumor biology. In our present study we examined the effects they exert on the expression patterns of miR-134, miR-132, miR-124-1, miR-9-3 and mTOR in the liver, spleen and kidney of mice treated with 7,12-dimethylbenz [a] anthracene (DMBA). Feeding of TFA-containing diet significantly increased the expression of all studied miRs and mTORC1 in all organs examined, except the expression of mTORC1 in the spleen and kidney. Diet containing olive oil significantly reduced the expression of miR-124-1, miR-9-3 and mTORC1 in the liver and spleen. In the kidney, apart from the mTORC1 gene, the expression of all miRs examined significantly decreased compared to the DMBA control. According to our results, the cell membrane protective, antioxidant, and anti-inflammatory effects of olive oil and the cell membrane damaging, inflammatory, and carcinogenic properties of TFA suggest negative feedback regulatory mechanisms. In contrast to our expectations, mTORC1 gene expression in the kidney has not been shown to be an appropriate biomarker–presumably, because the many complex effects that regulate mTOR expression may quench each other.
Background: Colorectal cancer is an increasing cause of death. Circulating microRNAs (miRs) could be great diagnostic and prognostic biomarkers of colorectal cancer, but further continuation of their utility is needed for their comprehensive application. Materials and Methods: Twentyseven patients with colonic cancer, 16 with rectal cancer and 12 healthy volunteers as controls, were involved in this study. and miR-29a were determined by reverse transcription polymerase chain reaction (RT-PCR) from sera of patients. Results: Expression of miR-155, miR-21 and miR-221 was significantly higher in rectal cancer than in colonic cancer. There was no difference found between those with TNM1 cancer and controls for both cancer types. miR-155, miR-34a and miR-29a were down-regulated in all patients with cancer compared to controls. We did not find any statistically significant up-regulation of miR-221 in patients with colonic cancer compared to controls. In contrast, in patients with rectal cancer, miR-221 expression was higher than in controls. Advanced stage was also linked to higher miR-221 expression compared to early stage. Slight, but statistically significant increase was observed in miR-30a expression in patients with colon cancer compared to control individuals. Conclusion: Our results partly support previous findings. Here we report on differences in the expression of circulating microRNA between colonic and rectal tumours for the first time. Colorectal tumours are becoming more and more significant 1333 This article is freely accessible online.
Background/Aim: Development of malignant tumors is preceded by molecular biological events. Our aim was to establish an assay panel by using miRNAs and other genes for the rapid screening of potential carcinogens or chemopreventive agents. Materials and Methods: Six male and 6 female CBA/Ca mice received 20 mg/bwkg 7,12dimethylbenz(α)anthracene (DMBA) intraperitoneally, and 24 h later RNA was isolated from parenchymal organs. Expression of miR-330, miR-29a, miR-9-1, miR-9-3 and mTORC1 was analysed by real time polymerase chain reaction and compared to non-treated controls. Results: DMBA caused significant alterations in the expression of the studied genes. The most profound changes were the strongly elevated miR-9-3 and mTORC1 expressions in female mice in all organs studied. Conclusion: miR-9-3 and mTORC1 expression in female mice were found to be the most suitable biomarkers for rapid identification of possible carcinogenic effects. According to estimates, in 2018 there were 18.1 million new malignant cancer cases and 9.6 million cancer deaths (1). According to WHO data, 30-50 % of all malignant tumors could be prevented (2), and early diagnosis would usually increase the chance of successful treatment.
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