Low Dietary n6/n3 Ratio Attenuates Changes in the NRF 2 Gene Expression, Lipid Peroxidation, and Inflammatory Markers Induced by Fructose Overconsumption in the Rat Abdominal Adipose Tissue.

The objective of this study was to examine the benefits of different n6/n3 polyunsaturated fatty acid ratios on the lipid metabolism, insulin resistance, and oxidative stress in the adipose tissue of rats fed a high-fructose diet. Male and female rats were divided into four groups: a control group (CON) (n6/n3 ratio ~7), a high-fructose group (HF) (n6/n3 ratio ~7), an N6-HF group (n6/n3 ratio ~50), and the DHA-HF group (n6/n3 ratio ~1, with the addition of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid). The CON group received plain water and the HF group received 15% fructose in their drinking water. Fructose induced an increase in the content of serum triglycerides, serum cholesterol, and HOMA-IR index. Among the fatty acids, elevated proportions of C18:1n9 and C16:1n7, as well as an increase in total monounsaturated fatty acid (MUFA), were found in the adipose tissue of the HF group. Fructose treatment also changed oxidative parameters, including a marked increase in the serum malondialdehyde (MDA) content. Meanwhile, DHA supplementation caused a significant decrease in the serum MDA concentration in comparison with the HF group. In addition, DHA/EPA supplementation attenuated oxidative stress by increasing NRF 2 gene expression. Fructose treatment also significantly decreased the adiponectin level, while DHA supplementation ameliorated it. The changes observed in this trial, including the decrease in the content of DHA and EPA, the decreased EPA/ARA ratio, and the increase in the expression of inflammatory genes, are characteristics of the low-grade inflammation caused by fructose treatment. These changes in the rat adipose tissue could be prevented by dietary intervention consisting of DHA supplementation and a low n6/n3 ratio.

Experimental and Computational Study of the Antioxidative Potential of Novel Nitro and Amino Substituted Benzimidazole/Benzothiazole-2-Carboxamides with Antiproliferative Activity.

We present the synthesis of a range of benzimidazole/benzothiazole-2-carboxamides with a variable number of methoxy and hydroxy groups, substituted with nitro, amino, or amino protonated moieties, which were evaluated for their antiproliferative activity in vitro and the antioxidant capacity. Antiproliferative features were tested on three human cancer cells, while the antioxidative activity was measured using 1,1-diphenyl-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) assays. Trimethoxy substituted benzimidazole-2-carboxamide 8 showed the most promising antiproliferative activity (IC50 = 0.6-2.0 µM), while trihydroxy substituted benzothiazole-2-carboxamide 29 was identified as the most promising antioxidant, being significantly more potent than the reference butylated hydroxytoluene BHT in both assays. Moreover, the latter also displays antioxidative activity in tumor cells. The measured antioxidative capacities were rationalized through density functional theory (DFT) calculations, showing that 29 owes its activity to the formation of two [O•∙∙∙H-O] hydrogen bonds in the formed radical. Systems 8 and 29 were both chosen as lead compounds for further optimization of the benzazole-2-carboxamide scaffold in order to develop more efficient antioxidants and/or systems with the antiproliferative activity.

High dietary n6/n3 ratio decreases eicosapentaenoic to arachidonic acid ratios and upregulates NFκB/p50 expression in short-term low-dose streptozotocin and high-fructose rat model of diabetes.

We studied the influence of dietary n6/n3 ratio and docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids supplementation on fatty acid profile, lipid peroxidation and NFκ/p50 expression in diabetes type 2. Treatments consisted of three dietary n6/n3 ratios: 6 (Control), 50 (high n6) and 1 (DHA and EPA supplemented). Half of the rats in each of the dietary treatments were made diabetic using the fructose/low-streptozotocin model. The Control and high n6 diets decreased EPA/ARA (arachidonic acid) ratios in the plasma and in the hepatic tissue suggesting proinflammatory fatty acid profile. The high n6 diet additionally increased the 4-HNE and NFκ/p50 expression in the hepatic tissue. These changes were the consequence of a decrease in the plasma content of DHA and EPA and an increase in the content of arachidonic acid in the liver neutral lipids. The supplementation with the DHA and EPA attenuated the change in EPA/ARA ratios, which imply the importance of the n6/n3 ratio in diabetes type 2.

Amino-Substituted Benzamide Derivatives as Promising Antioxidant Agents: A Combined Experimental and Computational Study.

We prepared a range of N-arylbenzamides with a variable number of methoxy and hydroxy groups, bearing either amino or amino-protonated moieties, and used DPPH and FRAP assays to evaluate their antioxidant capacity. Most of the systems exhibit improved antioxidative properties relative to the reference BHT molecule in both assays. Combining results from both sets of experiments, the most promising antioxidative potential was displayed by the trihydroxy derivative 26, which we propose as a lead compound for a further optimization of the benzamide scaffold. Computational analysis helped in interpreting the observed trends and demonstrated that protonated systems are better antioxidants than their neutral counterparts, while underlying the positive influence of the electron-donating methoxy group on the antioxidant properties, thus confirming the experiments. It also revealed that the introduction of the hydroxy groups shifts the reactivity from both amide and amine groups toward this moiety and additionally enhances antioxidative features. This is particularly evident in 26H•+, which owes its pronounced reactivity to the stabilizing [O•···H-O] hydrogen bonding between the created phenoxyl radical and the two neighboring hydroxy groups. We demonstrated that its antioxidative activities are more favorable than those for analogous trihydroxy derivatives without the N-phenyl group or without the amide moiety, which strongly justifies the employed strategy in utilizing bisphenylamides in designing potent antioxidants.