The aberrant crypt foci (ACF), cyclooxygenase 2 (COX-2), and the proliferating cell nuclear antigen (PCNA) are putative biomarkers for colon cancer. To study the association between light (1 g of ethanol/kg bw) and moderate (3 g of ethanol/kg bw) doses of ethanol with the chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), Wistar rats were divided into 6 groups. The colon fragments were collected for histochemical and immunohistochemical analyses, and the liver samples were collected for oxidative stress analysis, with products of lipid peroxidation (malondialdehyde), antioxidant enzymes (glutathione), and vitamin E. The association of light and moderate doses of ethanol with MNNG did not present differences in the oxidative parameters. However, a reduction in vitamin E levels in the carcinogen groups was observed. The association induced a reduction of the COX-2 and PCNA expression. The number of ACF in the group that received a light dose of ethanol had lower rates, while the group that received a moderate dose had the highest rates compared to the control MNNG, demonstrating that the light dose of ethanol could have a protective effect, while the moderate dose could represent a risk during chemical carcinogenesis in rats.
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.
Background: Obesity is associated with metabolic imbalance, including insulin resistance and endothelial dysfunction. Aim: We aimed to evaluate clinical and vascular parameters in obese with or without insulin resistance. Methods: Participants (n¼39) were divided into two groups according to Homeostasis Model Assessment-Insulin Resistance lower (group 1) or higher (group 2) than 2.7. All patients were submitted to clinical, anthropometric, biochemical, vascular structure and endothelial function assessment. Results: The mean age (53+9 vs. 52+7 years, p¼0.784) and body mass index (34.3+4.1 vs. 35.2+3.9 kg/m 2 , p¼0.464) were similar in both groups, and 74.4% were treated hypertensive subjects. Fasting glucose (84+7 vs. 97+18 mg/dl, p¼0.004) and insulin (9.32+2.48 vs. 22.74+7.49 mU/ml, p<0.001) were higher in group 2. Group 2 presented lower HDL-cholesterol (59+14 vs. 42+12 mg/dl, p<0.001) and higher triglycerides (122+87 vs. 191+112 mg/dl, p¼0.042) levels compared with group 1. HOMA-IR was correlated with abdominal circumference (r¼0.51, p¼0.001), abdominal/hip ratio (r¼0.57, p<0.001) and triglycerides/HDL ratio (r¼0.53, p¼0.001). Differences in brachial flow-mediated dilation did not reach statistical significance (10.2+6.2 vs. 7.9+4.7%, p¼0.245). Carotid intima-media thickness, carotid-femoral pulse wave velocity (8.5+1.9 vs. 9.1+1.5 m/s, p¼0.334) and central hemodynamic parameters were also similar between groups. Conclusion: Obese individuals with insulin resistance have higher visceral adiposity associated with impaired glucose and lipid metabolism. Endothelial function and arterial stiffness were similar between the groups, perhaps because of antihypertensive treatment in most of these subjects.
Acetaminophen (APAP) overdose promotes the formation of NAPQI, the depletion of liver glutathione and oxidative stress. N‐acetilcysteine (NAC) is a cysteine donator that is a precursor for the synthesis of GSH. Nrf2 is a transcription factor, important in antioxidant response pathway, promoting the expression of phase II enzyme and the regulation of liver GSH. Male C57 mices, were fasted for 16h prior to the application of APAP (250mg/kg). The treatment with NAC (204mg/kg) occurred 1h after APAP challenge. The collection of liver tissue occurred 24h after treatment. Analysis: Histopathology by score of necrosis fields; hepatic levels of GSH by spectrophotometry and hepatic levels of Vitamin E (VE) by HPLC; the gene expression of NFR2 by RT‐qPCR (Taqman probes). Statistic Analysis: Student. t test (Graphpad Prism 5.0). The group (ANAC) that received treatment with NAC 1h after APAP challenge, showed a reduction of 28% of necrosis (p <0.05). ANAC GSH levels were 1.5 higher than the APAP levels (p <0.05), although VE presents no differences between the groups. The Nfr2 gene expression fold change had almost doubled compared with APAP group (p <0.05). The results show that after the treatment with NAC, the increase of NFR2 gene expression promotes the increase of GSH levels, saving the reduction of VE and consequently, the oxidative stress, protecting the liver from necrosis. Support by FAPESP (2011/12749–0 & 2011/17616–9)
This study aimed to evaluate the effects of folic acid deprivation, fortification and supplementation followed by fortification in gene expression in colorectal carcinogenesis in rats.Wistar rats received either Standard AIN‐93M diet during all experiment (G1), diet without folic acid during all experiment (G2), diet with 3.25mg of folic acid during all experiment (G3) or diet with 5mg of folic acid before carcinogenesis induction followed by a diet with 3.25mg of folic acid through the experimental period (G4). Colorectal carcinogenesis was induced by 4 doses of MNNG (5mg/mL) twice a week during 2 weeks. Analysis: colonic S‐adenosylmetionine (SAM) and S‐adenosylhomocysteine (SAH) ratio; gene expression of Bax, CDKN1A, Bcl2. Statistical analysis: ANOVA, p<0.05. G3 had higher SAM than the other groups (p<0.05). G2 showed an increased SAH when compared to the other groups (p<0.001) and G3 had lower SAH than G4 (p<0.01). G3 presented elevated colonic SAM/SAH ratio in comparison to the other groups (p<0.05). G3 had increased Bax gene expression when compared to the other groups (p<0.05) and higher CDKN1A expression when compared to G1 and G4 (p<0.05). Bcl‐2 showed no difference among the groups studied (p>;0.05). Folic acid fortification (G3) seemed to improve the colorectal carcinogenesis biomarkers studied and modulate cell cycle and apoptosis gene expression. Financial Support: FAPESP
Introduction: Type 2 Diabetes (DM2) is a chronic conditionassociated with an increased risk of cardiovascular diseases,neuropathies, nephropathies and eye diseases. Incretins (GIPand GLP-1) are hormones important to insulin secretion, andtheir actions are compromised in DM2 patients. Objectives:This review considers the opportunities and challenges ofusing incretin mimetics in the treatment of DM2. Methods:Bibliographic review referring to the period from 2000 to2020, in electronic databases such as Scielo, Lilacs, PubMed,Web of Science. Results: Incretins stimulate insulin secretionby the pancreas in response to nutrient intake, with a lowerpotential to cause hypoglycemia. In addition, they have acardioprotective role, reducing blood pressure, improvingendothelial and myocardial function, and their use has beenassociated with a reduction in the risk of cardiovascularevents, including cardiovascular mortality. Clinical trialswith GLP-1R agonists (GLP-1RA) reduced albuminuria, increasednatriuresis, and decreased oxidative stress. In addition,treatment with incretin mimetics reduced the occurrence ofthe main cardiovascular outcomes related to atherosclerosis,promoted weight loss and improved lipid profile. Conclusion:Studies show the important role of incretin mimetics in thepathophysiology and treatment of DM2, with significanteffects in the cardiovascular system. However, its use must beevaluated in relation to its safety and to in which individualsthe benefits outweigh the risks associated with the treatment.Thus, its clinical relevance depends on studies with long-termfollow-up of patients, with analysis of its impact on mortalityand on the development of micro and macrovascularcomplications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.