The degree of food processing can influence serum fatty acid and lipid profiles in women with severe obesity.

Background: The increase in the prevalence of obesity is associated with the increase in the consumption of ultra-processed foods and may be related to the increase in the disorders involving metabolism and the transport and storage of fatty acids. Objective: To evaluate the effect of processed food consumption according to the degree of processing on the serum fatty acid levels and lipid profile of women with severe obesity. Methods: This was a cross-sectional study. Data were collected from anthropometric assessments, the food frequency questionnaire (FFQ), and blood tests for lipidogram studies and serum fatty acid measurements. The foods consumed were identified through the FFQ and classified according to the degree of processing based on the NOVA rating, and the frequencies of consumption were transformed into scores, as proposed by Fornés methodology. Data were analyzed using IBM SPSS Statistics, version 21. The significance level for the analysis was set at 5%. Results: This study included 44 women with a mean age of 40.59 years and mean body mass index of 48.61 kg/m2. An inverse association was observed between the consumption of unprocessed and the occurrence of hypertriglyceridemia (p = 0.021) and levels of triglycerides (p = 0.047), total cholesterol (p = 0.030), and very low-density lipoprotein-cholesterol (p = 0.039). The consumption of processed foods was positively associated with the presence of hypertriglyceridemia (p = 0.044) and omega 6/3 ratio (p = 0.001) and negatively associated with total omega 3 levels (p = 0.011). The consumption of processed foods was positively associated with total cholesterol (p = 0.041) and negatively associated with the omega 3/6 ratio (p = 0.001). A negative correlation was found between the average consumption of ultra-processed foods (at least once a week) and serum level of high-density lipoprotein (p = 0.035). Conclusion: The consumption of processed and ultra-processed foods was associated with unfavorable lipid profiles and fatty acid levels in women with severe obesity. These results emphasize the importance of promoting the consumption of unprocessed food to mitigate metabolic disorders linked to processed food intake.

Dietary inflammatory index and its relation to the pathophysiological aspects of obesity: a narrative review.

Obesity, a complex disease that involves energy imbalance and chronic low-grade inflammation, is implicated in the pathogenesis of several chronic non-communicable diseases. As dietary components modulate the human body's inflammatory status, the Dietary Inflammatory Index (DII®), a literature-derived dietary index, was developed in 2009 to characterize the inflammatory potential of a habitual diet. Abundant research has been conducted to investigate the associations between DII and obesity. In this narrative review, we examined the current state of the science regarding the relationships between DII and the inflammatory pathophysiological aspects related to obesity. DII is associated with inflammation in obesity. The most pro-inflammatory diet was directly related to higher levels of pro-inflammatory markers, which included C-reactive protein (CRP), interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α). Therefore, evidence suggests that the use of the DII may be useful for understanding the relationship between diet and the inflammatory process related to obesity.

The Influence of Single Nucleotide Polymorphisms On Body Weight Trajectory After Bariatric Surgery: A Systematic Review.

PURPOSE OF REVIEW: To conduct a systematic review to summarize the results of studies on this subject and to identify whether single nucleotide polymorphisms (SNPs) are good prognostic markers for body weight trajectory after bariatric surgery. RECENT FINDINGS: A considerable number of events can influence the body weight trajectory after bariatric surgery, and in the post-genomic era, genetic factors have been explored. This study is registered with PROSPERO (CRD42021240903). SNPs positively associated with poor weight loss after bariatric surgery were rs17702901, rs9939609, rs1360780, rs1126535, rs1137101, rs17782313, rs490683, and rs659366. Alternatively, SNPs rs2229616, rs5282087, rs490683, rs9819506, rs4771122, rs9939609, rs4846567, rs9930506, rs3813929, rs738409, rs696217, rs660339, rs659366, rs6265, rs1801260, and rs2419621 predicted a higher weight loss after bariatric surgery. Six studies performed with a genetic risk score (GRS) model presented significant associations between GRS and outcomes following bariatric surgery. This systematic review shows that, different SNPs and genetic models could be good predictors for body weight trajectory after bariatric surgery. Based on the results of the selected studies for this Systematic Review is possible to select SNPs and metabolic pathways of interest for the GRS construction to predict the outcome of bariatric surgery to be applied in future studies.

Association between the Processed Dietary Pattern and Tumor Staging in Patients Newly Diagnosed with Head and Neck Squamous Cell Carcinoma.

PURPOSE: This study aimed to assess the association between dietary patterns and tumor staging and the degree of cell differentiation in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: This cross-sectional study included 136 individuals newly diagnosed with different stages of HNSCC, aged 20- to 80 years-old. Dietary patterns were determined by principal component analysis (PCA), using data collected from a food frequency questionnaire (FFQ). Anthropometric, lifestyle, and clinicopathological data were collected from patients' medical records. Disease staging was categorized as initial stage (stages I and II), intermediary (stage III), and advanced (stage IV). Cell differentiation was categorized as poor, moderate, or well-differentiated. The association of dietary patterns with tumor staging and cell differentiation was evaluated using multinomial logistic regression models and adjusted for potential confounders. RESULTS: Three dietary patterns, "healthy," "processed," and "mixed," were identified. The "processed" dietary pattern was associated with intermediary (odds ratio (OR) 2.47; 95% confidence interval (CI) 1.43-4.26; p = 0.001) and advanced (OR 1.78; 95% CI 1.12-2.84; p = 0.015) staging. No association was found between dietary patterns and cell differentiation. CONCLUSION: A high adherence to dietary patterns based on processed foods is associated with advanced tumor staging in patients newly diagnosed with HNSCC.

Dietary inflammatory index and its relation to the pathophysiological aspects of obesity: a narrative review

ABSTRACT Obesity, a complex disease that involves energy imbalance and chronic low-grade inflammation, is implicated in the pathogenesis of several chronic non-communicable diseases. As dietary components modulate the human body's inflammatory status, the Dietary Inflammatory Index (DII®), a literature-derived dietary index, was developed in 2009 to characterize the inflammatory potential of a habitual diet. Abundant research has been conducted to investigate the associations between DII and obesity. In this narrative review, we examined the current state of the science regarding the relationships between DII and the inflammatory pathophysiological aspects related to obesity. DII is associated with inflammation in obesity. The most pro-inflammatory diet was directly related to higher levels of pro-inflammatory markers, which included C-reactive protein (CRP), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α). Therefore, evidence suggests that the use of the DII may be useful for understanding the relationship between diet and the inflammatory process related to obesity.

Polymorphism PLIN1 11482 G>A interacts with dietary intake to modulate anthropometric measures and lipid profile in adults with normal-weight obesity syndrome.

Evidence shows that genetic polymorphisms in perilipin 1 gene (PLIN1) are associated with excessive accumulation of body fat and disturbances in cardiometabolic markers. Therefore, the aim of this study was to verify whether the SNP PLIN1 11482 G>A (rs894160) interacts with nutrient intake, anthropometric, body composition and cardiometabolic markers in adults with normal-weight obesity (NWO) syndrome. A cross-sectional study was carried out with 116 individuals aged 20-59 years, with normal BMI and high percentage of body fat. Anthropometric and body composition measures, glycaemic control and serum lipid markers, SNP PLIN1 11482 G>A and nutrient intake were evaluated. Interactions between nutrient intake and the SNP were determined by regression models and adjusted for potential confounders. The SNP frequency was 56·0 % GG, 38·8 % GA and 5·2 % AA. Anthropometric measures and biochemical markers were not different according to genotype, except for total cholesterol (TC), LDL-cholesterol and non-HDL-cholesterol concentrations. However, important interactions between the SNP and dietary intake were observed. Carbohydrate intake interacted with the SNP PLIN1 11482 G>A to modulate waist circumference (WC) and the homeostatic model assessment of insulin resistance index. Interaction of lipid intake and the SNP modulated TC and LDL-cholesterol concentrations, and the interaction between protein intake and the SNP tended to modulate weight, WC and BMI. The SNP PLIN1 11482 G>A seems to modulate responses in anthropometric and lipid profile biomarkers of subjects with NWO depending on the dietary macronutrient composition, which may have long-term impact on cardiometabolic markers.

Dietary Intake is Associated with miR-31 and miR-375 Expression in Patients with Head and Neck Squamous Cell Carcinoma.

MicroRNAs (miRNAs) are important epigenetic regulators in head and neck squamous cell carcinoma (HNSCC), with miR-31 being considered an oncomir and miR-375, a tumor suppressor miR, which are up- and down-regulated in HNSCC, respectively. Nutrients are known to influence miRNA expression; however, this association is poorly explored in HNSCC. This work aimed to identify associations between dietary intake and the expression of miR-31 and miR-375 in patients newly diagnosed with HNSCC. The expression of miR-31 was positively associated with the consumption of iron (ß = 16.65) and vitamin C (ß = 0.37), and inversely associated with total sugar (ß = -0.88), cholesterol (ß= -0.23), vitamin B9 (ß= -0.37) and zinc (ß = -5.66) intake. The expression of miR-375 was positively associated with the consumption of selenium (ß = 1.52), vitamin C (ß = 0.17) and vitamin D (ß = 13.01), and inversely associated with the consumption of added sugar (ß = -0.49), phosphorus (ß= -0.27) and vitamin B12 (ß = -10.80). Our findings showed important associations between dietary intake and miR-31 and miR-375 expression in HNSCC, offering possible directions for further studies investigating how nutrients interfere with carcinogenesis.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1990972 .

Effect of dietary fat intake and genetic risk on glucose and insulin-related traits in Brazilian young adults.

PURPOSE: The development of metabolic diseases such as type 2 diabetes (T2D) is closely linked to a complex interplay between genetic and dietary factors. The prevalence of abdominal obesity, hyperinsulinemia, dyslipidaemia, and high blood pressure among Brazilian adolescents is increasing and hence, early lifestyle interventions targeting these factors might be an effective strategy to prevent or slow the progression of T2D. METHODS: We aimed to assess the interaction between dietary and genetic factors on metabolic disease-related traits in 200 healthy Brazilian young adults. Dietary intake was assessed using 3-day food records. Ten metabolic disease-related single nucleotide polymorphisms (SNPs) were used to construct a metabolic-genetic risk score (metabolic-GRS). RESULTS: We found significant interactions between the metabolic-GRS and total fat intake on fasting insulin level (Pinteraction = 0.017), insulin-glucose ratio (Pinteraction = 0.010) and HOMA-B (Pinteraction = 0.002), respectively, in addition to a borderline GRS-fat intake interaction on HOMA-IR (Pinteraction = 0.051). Within the high-fat intake category [37.98 ± 3.39% of total energy intake (TEI)], individuals with ≥ 5 risk alleles had increased fasting insulin level (P = 0.021), insulin-glucose ratio (P = 0.010), HOMA-B (P = 0.001) and HOMA-IR (P = 0.053) than those with < 5 risk alleles. CONCLUSION: Our study has demonstrated a novel GRS-fat intake interaction in young Brazilian adults, where individuals with higher genetic risk and fat intake had increased glucose and insulin-related traits than those with lower genetic risk. Large intervention and follow-up studies with an objective assessment of dietary factors are needed to confirm our findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00863-7.

Determination of genetic scores to estimate disturbances in circulating lipid profile biomarkers of adolescents: A preliminary report.

OBJECTIVE: The aim of this study was to develop genetic scores based on single-nucleotide polymorphisms (SNPs) related to lipid metabolism and evaluate whether they used to estimate disturbances in the circulating lipid profile biomarkers of adolescents. METHODS: In a preliminary cross-sectional approach, 113 Brazilian adolescents (10-19 y of age) with cardiovascular disease risk factors were evaluated. Genetic scores from 20 SNPs related to lipid metabolism were calculated by codifying each of them as the rescaled sum of risk allele frequencies. All scores were distributed in classes between 0 (absence of risk alleles) and 10 (presence of all risk alleles) to evaluate the additive effect of risk alleles on the lipid profile outcomes in the same interval. Multiple linear regression analyses were performed to evaluate the association between each score and blood lipid profile biomarkers. RESULTS: Significant associations between genetic scores and unfavorable outcomes in all evaluated lipid profile biomarkers were found. The mean ± SD of the genetic scores for the circulating lipid profile biomarkers in the 0 to 10 scale were 4.4 ± 2 for triacylglycerol, 5.3 ± 1.5 for total cholesterol, 5.6 ± 1.2 for high-density lipoprotein cholesterol, 4.9 ± 1.6 for low-density lipoprotein cholesterol, and 3.6 ± 1.9 for minimally modified low-density lipoprotein cholesterol. For each point obtained in each genetic score, a mean increase ± SE of 15.8 ± 4.2 mg/dL in triacylglycerol (P = 0.0001), 5.3 ± 1.7 mg/dL in total cholesterol (P = 0.0032), 4.8 ± 1.3 mg/dL in low-density lipoprotein cholesterol (P = 0.0003), and 1.1 ± 0.3 U/L in minimally modified low-density lipoprotein cholesterol (P = 0.0020) and a mean decrease of 3.7 ± 0.7 mg/dL in high-density lipoprotein cholesterol (P < 0.0001) concentrations were obtained. CONCLUSION: The calculated genetic scores could be used to estimate disturbances in circulating lipid profile biomarkers of adolescents and be applied in clinical practice to better target interventions to reduce cardiovascular disease risk throughout life.

Antiangiogenic effects of the chemopreventive agent tributyrin, a butyric acid prodrug, during the promotion phase of hepatocarcinogenesis.

Agents that inhibit angiogenic factors may prevent the development of hepatocellular carcinoma (HCC). Thus, the objective of this study was to kinetically evaluate the antiangiogenic activity of tributyrin (TB), a butyric acid prodrug, in the promotion stage of hepatocarcinogenesis. For this purpose, the resistant hepatocyte (RH) model was used for induction of preneoplastic lesions in Wistar rats. During the promotion phase, the animals received TB or maltodextrin (MD) as control daily. The rats were killed at three time-points (P1, P2 and P3). Increased expression of Vegfa and Vegfr2 was observed during promotion phase of hepatocarcinogenesis, which was not reversed by TB treatment. However, TB treatment reduced the expression of cluster of differentiation (CD) 34-positive vessels at P3 and α-smooth muscle actin (α-SMA)-positive vessels at P2 compared with MD. Enhanced levels of hypoxia inducible factor-1α (HIF-1α) and phosphorylated extracellular signal-regulated kinases (pERK) were detected at P3 when compared with P1 and P2 in the MD treatment. TB treatment reduced the levels of HIF-1α and pERK at P3 relative to the MD control. Experiments with human umbilical vein endothelial cells (HUVEC) showed that sodium butyrate (NaBu) inhibited cell migration and tube formation, confirming the antiangiogenic activity of its prodrug TB. In conclusion, antiangiogenic activity of TB is an early event that already occurs in preneoplastic livers, reinforcing its potential chemopreventive effects against HCC.

APOE genotype associates with food consumption and body composition to predict dyslipidaemia in Brazilian adults with normal-weight obesity syndrome.

BACKGROUND & AIM: Normal-Weight Obesity Syndrome has been characterized by a normal body mass index and high percentage of body fat. It is associated with an increased risk of cardiovascular disease development. This study aimed to evaluate whether apolipoprotein E (APOE) genotypes and food consumption are related to the lipid profiles of adults with Normal-Weight Obesity Syndrome. METHODS: Analytical cross-sectional study, including adults with Normal-Weight Obesity Syndrome. Socioeconomic, health and lifestyle questionnaires were administered. Anthropometric variables, body composition and blood pressure were evaluated. Dietary intake, lipid profile and genotyping of polymorphisms rs7412 and rs429358 in the APOE gene were evaluated. RESULTS: Only 6.0% of women and none of the men had increased waist circumference (≥80 cm for women and ≥94 cm for men). No women and 6.2% of men had altered blood pressure (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg). When the traditional lipid profile was assessed, 52.5% of individuals presented dyslipidaemia. When the levels of apolipoproteins A1 and B were included, the prevalence was 73.0%. Regression analysis showed a positive relationship between the presence of allele ε2 and apolipoprotein A1 levels (95% CI = 4.2 to 38.3; p = 0.015) and between the ε4 allele and apolipoprotein B (ε4 versus ε2: 95% CI = 0.08 to 29.5; p = 0.049 and ε4 versus ε3: 95% CI = 0.6 to 17.6; p = 0.036). Carriers of the ε2 allele had a 75.0% lower probability of presenting dyslipidaemia compared with ε3ε3 individuals (95% CI = 0.04 to 0.8; p = 0.027). Relationships between body fat, food consumption and lipid profile were observed and differed among genotypes. CONCLUSIONS: APOE genotype and food consumption were associated with lipid profile. This was the first study to evaluate the APOE genotype and to analyze relationships between genetic profile, food intake and lipid profile of subjects with Normal-Weight Obesity Syndrome.

Polymorphisms in PPARG and APOE: relationships with lipid profile of adolescents with cardiovascular risk factors

BACKGROUND: Cardiovascular diseases constitute the main death cause worldwide resulting from a combination of genetic and lifestyle factors, and the prevalence among younger individuals has increased. It is important to early identify changes in lipid profile and the influence of genetic variations in specific genes on the individual patterns of lipid profile. Thus, the aim of this study was to verify the relationship of polymorphisms in PPAR-gamma gene (PPARG−rs1801282−Pro12Ala) and in apolipoprotein E gene (APOE−rs429358 + rs7412, determinants of the APOE2, APOE3, or APOE4 genotypes) with lipid profile of adolescents under cardiovascular risk factors. METHODS: This was a cross-sectional study with 115 adolescents aged 10­19 years, which presented cardiovascular risk factors. The students were evaluated regarding socioeconomic, anthropometric, biochemical, genetic, and dietetic variables. Student'sttest or Mann-Whitney test were applied to the analysis of the genotypes. Multiple linear regression analysis was performed to determine the variables that most influenced the lipid profile. RESULTS: Adolescents carrying PPARG Ala allele showed higher serum triglycerides (p= 0.0423) and very low-density lipoprotein (p= 0.0410) levels when compared to those carrying the wild genotype. For the APOE polymorphism, it was observed a trend of higher triglycerides (p= 0.0712) and very low-density lipoprotein (p= 0.0758) levels in the adolescents carrying the E4 allele when compared to those who did not carry this allele. CONCLUSION: The polymorphisms PPARGrs1801282 andAPOErs429358 + rs7412 seem to be related to the development of lipid profile alterations in adolescents.

Brazilian Society for Food and Nutrition position statement: nutrigenetic tests

Position statement: The Brazilian Society for Food and Nutrition (SBAN) bases the following position statement on acritical analysis of the literature on nutritional genomics and nutrigenetic tests: (1) Nutrigenetic tests are predictive and not diagnostic, should not replace other evaluations required to treatment, and should only be used as an additional tool to nutritional prescription; (2) Nutritionists/registered dietitians and other health professionals must be able to interpret the nutrigenetic tests and properly guide their patients, as well as build their professional practice ongeneral ethical principles and those established by regulatory authorities; (3) It is extremely important to highlight that them is interpretation of nutrigenetic tests can cause psychological and health problems to the patient; (4) Currently, there is insufficient scientific evidence for the recommendation of dietary planning and nutritional supplementation based only on nutrigenetic tests. This position statement has been externally reviewed and approved by the board of SBAN and has not gone through the journal's standard peer review process.

Suppressing activity of tributyrin on hepatocarcinogenesis is associated with inhibiting the p53-CRM1 interaction and changing the cellular compartmentalization of p53 protein.

Hepatocellular carcinoma (HCC), an aggressive and the fastest growing life-threatening cancer worldwide, is often diagnosed at intermediate or advanced stages of the disease, which substantially limits therapeutic approaches for its successful treatment. This indicates that the prevention of hepatocarcinogenesis is probably the most promising approach to reduce both the HCC incidence and cancer-related mortality. In previous studies, we demonstrated a potent chemopreventive effect of tributyrin, a butyric acid prodrug, on experimental hepatocarcinogenesis. The cancer-inhibitory effect of tributyrin was linked to the suppression of sustained cell proliferation and induction of apoptotic cell death driven by an activation of the p53 apoptotic signaling pathway. The goal of the present study was to investigate the underlying molecular mechanisms linked to tributyrin-mediated p53 activation. Using in vivo and in vitro models of liver cancer, we demonstrate that an increase in the level of p53 protein in nuclei, a decrease in the level of cytoplasmic p53, and, consequently, an increase in the ratio of nuclear/cytoplasmic p53 in rat preneoplastic livers and in rat and human HCC cell lines caused by tributyrin or sodium butyrate treatments was associated with a marked increase in the level of nuclear chromosome region maintenance 1 (CRM1) protein. Mechanistically, the increase in the level of nuclear p53 protein was associated with a substantially reduced binding interaction between CRM1 and p53. The results demonstrate that the cancer-inhibitory activity of sodium butyrate and its derivatives on liver carcinogenesis may be attributed to retention of p53 and CRM1 proteins in the nucleus, an event that may trigger activation of p53-mediated apoptotic cell death in neoplastic cells.

Expression of miR-296-5p as predictive marker for radiotherapy resistance in early-stage laryngeal carcinoma.

PURPOSE: Definitive radiation therapy is the mainstay of treatment for early stage laryngeal squamous cell carcinoma (LSCC). However, up to 30% of the patients do not respond to radiotherapy. Unfortunately, we are unable to predict which tumors are likely to respond to radiation, and which will be resistant and persist. Therefore, the development of novel markers to predict response to radiotherapy is urgently needed. This study was designed to evaluate the expression pattern of microRNAs (miRNAs) in LSCC in order to identify markers capable of segregating radioresistant and radiosensitive tumors and to investigate the relationship between the expression of these miRNAs and the prognosis of LSCC. METHODS: The expression profile of 667 miRNAs was determined in an initial screening of nine early-stage LSCC samples (5 radioresistant and 4 radiosensitive) using TaqMan Low-Density Array (TLDA). Real-time polymerase chain reactions were performed to validate the expression of selected miRNAs in an expanded LSCC cohort (20 radioresistant and 14 radiosensitive). The miRNA expression level was scored as high or low based on the median of the expression in the LSCC samples. RESULTS: A comprehensive miRNA expression profiling enabled the identification of four miRNAs (miR-296-5p miR-452, miR-183* and miR-200c) differentially expressed in radioresistant LSCC. Moreover, the analysis of additional 34 LSCC samples, confirmed the expression of miR-296-5p as significantly related to radioresistance (p = 0.002) as well as an association of this marker with recurrence (p = 0.025) in early stage laryngeal cancer. CONCLUSIONS: This study indicates that miR-296-5p expression is associated with resistance to radiotherapy and tumor recurrence in early stage LSCC, showing the feasibility of this marker as a novel prognostic factor for this malignance. Furthermore, miR-296-5p expression could be helpful in the identification of tumors resistant to radiotherapy; thus aiding the clinicians in the choice of the best therapeutic scheme to be used in each case.

ß-ionone inhibits persistent preneoplastic lesions during the early promotion phase of rat hepatocarcinogenesis: TGF-α, NF-κB, and p53 as cellular targets.

Dietary isoprenic derivatives such as ß-ionone (ßI) are a promising class of chemopreventive agents. In this study, cellular aspects of ßI protective activities during early hepatocarcinogenesis were evaluated. Male Wistar rats were submitted to "resistant hepatocyte" model and then received daily 16 mg/100 g body weight (b.w.) of ßI (ßI group) or only 0.25 mL/100 g b.w. of corn oil (vehicle, control group [CO]) during 4 wk, specifically during early promotion phase. Compared to controls, ßI inhibited (P < 0.05) the development of persistent preneoplastic lesions (pPNL), considered to be potential hepatocellular carcinoma (HCC) progression sites, and increased remodeling PNL (rPNL) (P < 0.05) that tend to regress to a normal phenotype. Increased ßI hepatic levels (P < 0.05), in the ßI group, were associated with its chemopreventive actions. Compared to control rats, ßI reduced the frequency of both pPNL and rPNL positive for tumor growth factor (TGF)-α (P < 0.05), reduced the frequency of pPNL stained for p65 (nuclear factor-kappaB; NF-κB) (P < 0.05), and reduced the frequency of pPNL positive for cytoplasmic p53 (P < 0.05). Our data demonstrated that ßI targets TGF-α, NF-κB, and p53 in initial phases of hepatocarcinogenesis and specifically inhibits PNL with increased probability to progress to HCC. This isoprenoid may represent a chemopreventive agent of choice for HCC control.

Chemopreventive effects of ß-ionone and geraniol during rat hepatocarcinogenesis promotion: distinct actions on cell proliferation, apoptosis, HMGCoA reductase, and RhoA.

Chemopreventive activities of the dietary isoprenoids ß-ionone (ßI) and geraniol (GOH) were evaluated during the promotion phase of hepatocarcinogenesis. Over 5 consecutive weeks, rats received daily 16 mg/100 g body weight (b.w.) of ßI (ßI group), 25 mg/100 g b.w. of GOH (GOH group), or only corn oil (CO group, controls). Compared to the CO group, the following was observed: only the ßI group showed a decrease in the mean number of visible hepatocyte nodules (P<.05); ßI and GOH groups had reduced mean number of persistent preneoplastic lesions (pPNLs) (P<.05), but no differences regarding number of remodeling PNL (rPNLs) were observed; only the ßI group exhibited smaller rPNL size and percentage of liver sections occupied by pPNLs (P<.05), whereas the GOH group displayed a smaller percentage of liver sections occupied by rPNLs (P<.05); a trend was observed in the ßI group, which showed reduced cell proliferation of pPNLs (P<.10), and the GOH group had increased apoptosis in pPNLs and rPNLs (P<.05); only the ßI group displayed reduced total plasma cholesterol concentrations (P<.05) and increased hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase mRNA levels (P<.05); only the GOH group had lower hepatic membrane RhoA protein levels (P<.05); both the ßI- and GOH-treated groups had higher hepatic concentrations of ßI and GOH, respectively (P<.05). Given these data, ßI and GOH show promising chemopreventive effects during promotion of hepatocarcinogenesis by acting through distinct mechanism of actions: ßI may inhibit cell proliferation and modulate HMGCoA reductase, and GOH can induce apoptosis and inhibit RhoA activation.

Chemoprevention of rat hepatocarcinogenesis with histone deacetylase inhibitors: efficacy of tributyrin, a butyric acid prodrug.

Hepatocellular carcinoma (HCC) ranks in prevalence and mortality among top 10 cancers worldwide. Butyric acid (BA), a member of histone deacetylase inhibitors (HDACi) has been proposed as an anticarcinogenic agent. However, its short half-life is a therapeutical limitation. This problem could be circumvented with tributyrin (TB), a proposed BA prodrug. To investigate TB effectiveness for chemoprevention, rats were treated with the compound during initial phases of "resistant hepatocyte" model of hepatocarcinogenesis, and cellular and molecular parameters were evaluated. TB inhibited (p < 0.05) development of hepatic preneoplastic lesions (PNL) including persistent ones considered HCC progression sites. TB increased (p < 0.05) PNL remodeling, a process whereby they tend to disappear. TB did not inhibit cell proliferation in PNL, but induced (p < 0.05) apoptosis in remodeling ones. Compared to controls, rats treated with TB presented increased (p < 0.05) hepatic levels of BA indicating its effectiveness as a prodrug. Molecular mechanisms of TB-induced hepatocarcinogenesis chemoprevention were investigated. TB increased (p < 0.05) hepatic nuclear histone H3K9 hyperacetylation specifically in PNL and p21 protein expression, which could be associated with inhibitory HDAC effects. Moreover, it reduced (p < 0.05) the frequency of persistent PNL with aberrant cytoplasmic p53 accumulation, an alteration associated with increased malignancy. Original data observed in our study support the effectiveness of TB as a prodrug of BA and as an HDACi in hepatocarcinogenesis chemoprevention. Besides histone acetylation and p21 restored expression, molecular mechanisms involved with TB anticarcinogenic actions could also be related to modulation of p53 pathways.

Inibição de danos em DNA e alteração da expressão gênica em ratos Wistar tratados com as hortaliças couve e repolho (Brassica oleracea) e submetidos à hepatocarcinogênese química / Inhibition in DNA damages and differential gene expression in Wistar rats treated with kale and cabbage(Brassica oleracea) and submitted to chemical hepatocarcinogenesis

O câncer é a segunda maior causa de morte no mundo, sendo responsável por aproximadamente 7,6 milhões de óbitos. Entretanto, pesquisadores alertam para uma associação inversa entre o consume de frutas e hortaliças e o desenvolvimento de neoplasias, desta forma a organização mundial da saúde sugere, dentre outras medidas para controle do câncer, o aumento do consumo de frutas e hortaliças. Nesse contexto o objetivo deste trabalho foi avaliar os eventuais efeitos quimiopreventivos das hortaliças Brassicas, couve (C) e repolho (R). Realizaram-se dois experimentos sendo o primeiro, o modelo de hepatocarcinogênese de Ito, onde as hortaliças foram fornecidas durante 8 semanas na água de beber (10% p/v), animais que receberam apenas água foram utilizados como controle. Nesse experimento não houve inibição (P < 0,05) de lesões pré-neoplásicas hepáticas positivas para glutationa S-transferase forma placental e não houve indução (P < 0,05) da apoptose nos grupos tratados com C ou R. Contudo, observou-se redução (P > 0,05) de danos em DNA hepático e aumento (P > 0,05) da concentração hepática de luteína de ratos tratados com C e R, quando comparados a ratos controle. No segundo experimento as hortaliças foram fornecidas durante 8 semanas na água de beber (20% p/v) , e os animais foram submetidos a aplicação do carcinogênico hepático 24h antes da eutanásia. Não houve redução (P > 0,05) de danos em DNA, contudo a concentração do aduto de DNA 8-hidroxi-2-deoxiguanosina (8OHdG) e foi elevada (P < 0,05) em animais tratados com R quando comparados a tratados com C e controles. Com relação à expressão diferencial de genes, 29 genes foram diferencialmente expressos em fígado, dentre eles o gene da 8-oxoguanina-DNA-glicosilase (enzima de reparo do DNA), foi hipoexpressa no grupo tratado com R, o que pode explicar o aumentado valor de adutos no mesmo grupo. O cólon apresentou 31 genes com diferença de expressão, onde 5 genes estão relacionados ao metabolismo de xenobióticos.