Diet-induced Oxidative Stress Research Articles

Hericium erinaceus Protein Alleviates High-Fat Diet-Induced Hepatic Lipid Accumulation and Oxidative Stress In Vivo

Hericium erinaceus Protein Alleviates High-Fat Diet-Induced Hepatic Lipid Accumulation and Oxidative Stress In Vivo

Macadamia (Macadamia integrifolia) Oil Prevents High-Fat Diet-Induced Lipid Accumulation and Oxidative Stress by Activating the AMPK/Nrf2 Pathway.

Hyperlipidemia, characterized by an abnormal lipid metabolism, is related to multiple cardiovascular diseases that pose challenges to global public health. Macadamia oil (MO), rich in monounsaturated fatty acids (around 80%), is regarded as a functional oil used to regulate lipid accumulation. Nonetheless, the lipid-lowering mechanism of MO is still unknown. Therefore, the lipid-lowering effects of MO in high-fat diet (HFD)-induced hyperlipidemic mice were evaluated in this study. The results revealed that MO could effectively reduce body weight and the organ index and improve serum lipid levels by reducing total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels and elevating high-density lipoprotein cholesterol levels. Additionally, MO supplementation could improve abnormal liver function caused by hyperlipemia, characterized by decreased liver enzyme levels, including alanine aminotransferase and aspartate aminotransferase. Meanwhile, MO also exhibited an inhibitory effect on oxidative stress and lipid accumulation caused by an HFD. Moreover, findings from qRT-PCR and Western blotting analyses suggest that MO supplementation markedly prevented hyperlipidemia by inhibiting the expression of AMPK pathway-related genes, SREBP-1c, FAS, ACC, and PPAR-γ, as well as upregulating the levels of Nrf2, HO-1, and γ-GCS. These results indicate that MO attenuates lipid accumulation in vivo via AMPK/Nrf2 pathway activation, suggesting that MO could serve as a dietary supplementation or medication for treating hyperlipidemia.

Exploring the ameliorative potential of rutin against High-Sucrose Diet-induced oxidative stress and reproductive toxicity in Drosophila melanogaster

Sucrose is a vital ingredient in numerous food items consumed regularly. However, exposure to excessive sucrose for a prolonged period can promote health issues. The reproductive system has a delicate physiology that can be targeted by various chemical stressors, including sucrose. Hence, the present in vivo study aims to unveil the impacts of High-Sucrose Diet (HSD) on the reproductive fitness of Drosophila melanogaster. In addition, the present work has also assessed the protective potential of a bioactive compound, rutin, against it. Here, first instar larvae were exposed to HSD (30 %) alone and in combination with rutin (100–300 µM) till their adult stage. HSD disturbed sex comb morphology in adult males, while fecundity and hatchability of eggs in females. Moreover, HSD triggered gonadal ROS production, oxidative stress, and modulated endogenous antioxidants such as SOD, catalase, and glutathione in both sexes. Nuclear fragmentation and tissue injuries, along with protein and lipid oxidation, were also apparent. Elevated levels of cytosolic Iron suggested an active Fenton reaction in adults. Further, HSD modulated the activities of reproductive and metabolic mediators, including vitellogenin, malate dehydrogenase, glucose-6-phosphate dehydrogenase, and angiotensin-converting enzymes that are critical to maintain the overall reproductive fitness. Interestingly, co-treatment with rutin, mainly at 200 µM, mitigated these adverse effects and restored reproductive fitness. The protective potential of rutin might be attributed to its ability to normalize redox homeostasis, reduce oxidative stress, and optimize critical enzymes involved in reproductive physiology. These findings suggest that rutin has potential therapeutic implications for counteracting the reproductive hazards induced by HSD.

Positive impact of indicaxanthin from Opuntia ficus-indica fruit on high-fat diet-induced neuronal damage and gut microbiota dysbiosis.

Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet; the high-fat diet group was fed a high-fat diet; and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally (0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet-induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids (Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles (Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet-induced neuronal damage and on the gut microbiota composition in obese mice.

Diet induced mitochondrial DNA replication instability in Rad51c mutant mice drives sex-bias in anemia of inflammation.

Anemia of inflammation (AI) is a common comorbidity associated with obesity, diabetes, cardiac disease, aging, and during anti-cancer therapies. Mounting evidence illustrates that males are disproportionally affected by AI, but not why. Here we demonstrate a molecular cause for a sex-bias in inflammation. The data shows that mitochondrial DNA (mtDNA) instability induced by dietary stress causes anemia associated with inflamed macrophages and improper iron recycling in mice. These phenotypes are enhanced in mice with mutations in Fanco/Rad51c , which predisposes to the progeroid disease Fanconi Anemia. The data reveals a striking sex-bias whereby females are protected. We find that estrogen acts as a mitochondrial antioxidant that reduces diet-induced oxidative stress, mtDNA replication instability and the distinctively mtDNA-dependent unphosphorylated STAT1 response. Consequently, treatment of male Rad51c mutant mice with estrogen or mitochondrial antioxidants suppresses the inflammation-induced anemia. Collectively, this study uncovers estrogen-responsive mtDNA replication instability as a cause for sex-specific inflammatory responses and molecular driver for AI.

Hesperidin Protects from High-Fat Diet-induced Oxidative Stress in Experimental Hyperlipidemic Wistar Rats

Hesperidin Protects from High-Fat Diet-induced Oxidative Stress in Experimental Hyperlipidemic Wistar Rats

Protective effect of β-sitosterol against high-fructose diet-induced oxidative stress, and hepatorenal derangements in growing female sprague-dawley rats

BackgroundChronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed.ResultsHigh fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman’s capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function.Conclusionsβ-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.

Reversal of high-fat diet-induced cognitive impairment and oxidative stress in the brain through Zingiber officinale supplementation.

Obesity is a significant health concern that is correlated with various adverse health outcomes. Diet-induced obesity (DIO) is associated with impaired cognitive function. Pharmacological treatments for obesity are limited and may have serious adverse effects. Zingiber officinale (ZO) has anti-inflammatory and antioxidant effects, in addition to metabolic effects. This study aimed to assess the effects of Zingiber officinale supplementation on cognitive function, anxiety levels, neurotrophin levels, and the inflammatory and oxidative status in the cortex following DIO in mice. Two-month-old male Swiss mice were fed DIO or standard chow for 4 months and subsequently subdivided into the following groups (n = 10 mice/group): (i) control - vehicle (CNT + vehicle); (ii) CNT supplemented with ZO (CNT + ZO); (iii) obese mice (DIO + vehicle); and (iv) obese mice supplemented with ZO (DIO + ZO) (n = 10). Zingiber officinale extract (400mg/kg/day) was administered for 35 days via oral gavage. The DIO + vehicle group exhibited impaired recognition memory. The CNT + ZO group presented a greater number of crossings in the open field. No difference between the groups was observed in the plus maze test. DIO + vehicle increased the DCFH and carbonylation levels in the cortex. The DIO + vehicle group presented a reduction in catalase activity. The expression of inflammatory or neurotrophin markers in the cerebral cortex was not different. In conclusion, our findings indicate that supplementation with ZO reverses the cognitive impairment in DIO mice and enhances the antioxidant status of the cerebral cortex.

Urine metabolomics unravel the effects of short-term dietary interventions on oxidative stress and inflammation: a randomized controlled crossover trial

Dietary biomarkers in urine remain elusive when evaluating diet-induced oxidative stress and inflammation. In our previous study, we conducted a randomized controlled crossover trial to compare the short-term (4-weeks) effects of the balanced Korean diet (BKD) with Western diets, including the 2010 dietary guidelines for Americans (2010 DGA) and typical American diet (TAD), on various metabolic indices in obese Korean adults. Building on this work, the current research focuses on the impact of these dietary interventions on oxidative stress (d-ROMs and BAP) and inflammation (CRP, TNF-α, IL-6, IL-1β, MCP-1) biomarkers in serum, and the concurrent urine metabolomes. Each dietary regimen was in silico and experimentally examined for their antioxidant levels using ABTS, DPPH, and FRAP assays, as well as total flavonoid (TFC) and total phenolic (TPC) contents. We assessed post-intervention variations in oxidative stress and inflammation biomarkers in serum, as well as the urine metabolite profiles for the participants (n = 48, average age: 41 years). Antioxidant contents and associated total antioxidant capacity (TAC) were significantly higher for the recommended diets (BKD and 2010 DGA) compared to TAD (p < 0.05). Butanol extracts from recommended diets (BKD and 2010 DGA) showed significantly higher antioxidant activity compared to TAD in ABTS (p < 0.01), DPPH, and FRAP (p < 0.05) assays. Consistent results were observed in total phenolic and flavonoid contents, mirroring their respective antioxidant activities. Following the intervention period, oxidative stress & inflammation markers in serum varied marginally, however, the urine metabolite profiles were clearly demarcated for the BKD and Western dietary groups (PC1 = 5.41%). For BKD group, the pre- and post-intervention urine metabolite profiles were clearly segregated (PLS2 = 2.93%). Compared to TAD, urine extracts from the recommended dietary group showed higher abundance of benzoic acid & phenolic derivatives (VIP > 0.7, p < 0.05). Metabolites associated with oxidative stress were observed higher in the urine samples from Western dietary groups compared to BKD. Urine metabolomics data delineated the post-intervention effects of three dietary interventions which corroborates the respective findings for their effects on metabolic indices.

Dietary Chitosan Attenuates High-Fat Diet-Induced Oxidative Stress, Apoptosis, and Inflammation in Nile Tilapia (Oreochromis niloticus) through Regulation of Nrf2/Kaep1 and Bcl-2/Bax Pathways.

Fatty liver injury is a prevalent condition in most farmed fish, yet the molecular mechanisms underpinning this pathology remain largely elusive. A comprehensive feeding trial spanning eight weeks was conducted to discern the potential of dietary chitosan in mitigating the deleterious effects of a high-fat diet (HFD) while concurrently exploring the underlying mechanism. Growth performance, haemato-biochemical capacity, antioxidant capacity, apoptotic/anti-apoptotic gene expression, inflammatory gene expression, and histopathological changes in the liver, kidney, and intestine were meticulously assessed in Nile tilapia. Six experimental diets were formulated with varying concentrations of chitosan. The first three groups were administered a diet comprising 6% fat with chitosan concentrations of 0%, 5%, and 10% and were designated as F6Ch0, F6Ch5, and F6Ch10, respectively. Conversely, the fourth, fifth, and sixth groups were fed a diet containing 12% fat with chitosan concentrations of 0%, 5%, and 10%, respectively, for 60 days and were termed F12Ch0, F12Ch5, and F12Ch10. The results showed that fish fed an HFD demonstrated enhanced growth rates and a significant accumulation of fat in the perivisceral tissue, accompanied by markedly elevated serum hepatic injury biomarkers and serum lipid levels, along with upregulation of pro-apoptotic and inflammatory markers. In stark contrast, the expression levels of nrf2, sod, gpx, and bcl-2 were notably decreased when compared with the control normal fat group. These observations were accompanied by marked diffuse hepatic steatosis, diffuse tubular damage, and shortened intestinal villi. Intriguingly, chitosan supplementation effectively mitigated the aforementioned findings and alleviated intestinal injury by upregulating the expression of tight junction-related genes. It could be concluded that dietary chitosan alleviates the adverse impacts of an HFD on the liver, kidney, and intestine by modulating the impaired antioxidant defense system, inflammation, and apoptosis through the variation in nrf2 and cox2 signaling pathways.

Short-term feeding of high-fat diet induces neuroinflammation and oxidative stress in arcuate nucleus in rats

Objectives: This study aimed to compare the effects of high-fat diet-induced neuroinflammation and oxidative stress in the arcuate nucleus (ARC) of obese-prone and obese-resistant rats. Materials and Methods: Rats were divided into obese-prone and obese-resistant groups based on their initial body weight. They were then fed either a 5% or 60% fat-containing diet. In the ARC, the expression of inflammatory markers [Interleukin (IL-6); Nuclear Factor Kappa-B Inhibitor Alpha (NFKBIA); Cluster of Differentiation (CD)-66; and mucin-like hormone receptor-like 1 (EMR-1)], as well as levels of reactive oxygen species (ROS) and antioxidant enzymes (glutathione and glutathione peroxidase and superoxide dismutase), was assessed along with body weight, blood glucose, Homeostatic Model Assessment for Insulin Resistance, plasma insulin and plasma leptin levels after ten days of intervention. Results: The results showed a significantly higher expression of inflammatory markers in the ARC of high-fat diet-induced obese rats after ten days. Body weight, plasma insulin, plasma leptin and hydrogen peroxide production were also significantly higher in obese-prone rats fed a high-fat diet. Conclusion: In conclusion, this study demonstrates that short-term consumption of a high-fat diet can lead to hypothalamic inflammation and ROS production in the ARC of rats. Obese-prone rats exhibited hyperinsulinaemia and hyperleptinaemia after short-term high-fat diet consumption.

Alantolactone attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is a chronic disease with an increasing incidence, which can further develop into liver fibrosis and hepatocellular carcinoma at the end stage. Alantolactone (Ala), a sesquiterpene lactone isolated from Asteraceae, has shown anti-inflammatory effects in different models. However, the therapeutic effect of Ala on NAFLD is not clear.MethodsC57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD. After 16 weeks, Ala was administered by gavage to observe its effect on NAFLD. RNA sequencing of liver tissues was performed to investigate the mechanism. In vitro, mouse cell line AML-12 was pretreated with Ala to resist palmitic acid (PA)-induced inflammation, oxidative stress and fibrosis.ResultsAla significantly inhibited inflammation, fibrosis and oxidative stress in HFD-induced mice, as well as PA-induced AML-12 cells. Mechanistic studies showed that the effect of Ala was related to the induction of Nrf2 and the inhibition of NF-κB. Taken together, these findings suggested that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress.ConclusionsThe study found that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress, suggesting that Ala is an effective therapy for NAFLD.

Bound Polyphenols of Oat Bran Released by Gut Microbiota Mitigate High Fat Diet-Induced Oxidative Stress and Strengthen the Gut Barrier via the Colonic ROS/Akt/Nrf2 Pathway.

Whole-grain foods are rich in bound polyphenols (BPs) whose health benefits were largely underestimated compared with free polyphenols. We first found that DFBP (dietary fiber with BPs from oat bran) exhibited stronger colonic antioxidant activities than DF. 16S rRNA sequencing showed that DFBP selectively changed gut microbial composition, which reciprocally released BPs from DFBP. Released polyphenols from DFBP reduced excessive colonic ROS and exhibited colonic antioxidant activities via the ROS/Akt/Nrf2 pathway revealed by transcriptome and western blot analysis. Colonic antioxidant activities of DFBP mediated by gut microbiota were next proven by treating mice with broad-spectrum antibiotics. Next, Clostridium butyricum, as a distinguished bacterium after DFBP intervention, improved colonic antioxidant capacities synergistically with DFBP in HFD-fed mice. This was explained by the upregulated mRNA expression of esterase, and cellulase of Clostridium butyricum participated in releasing BPs. Our results would provide a solid basis for explaining the health benefits of whole grains.

Antioxidative Potential and Ameliorative Effects of Rice Bran Fermented with Lactobacillus against High-Fat Diet-Induced Oxidative Stress in Mice.

Rice bran is an important byproduct of the rice polishing process, rich in nutrients, but it is underutilized and often used as feed or discarded, resulting in a huge amount of waste. In this study, rice bran was fermented by Lactobacillus fermentum MF423 to obtain a product with high antioxidant activity. First, a reliable and efficient method for assessing the antioxidant capacity of the fermentation products was established using high-performance liquid chromatography (HPLC), which ensured the consistency of the batch fermentation. The fermented rice bran product (FLRB) exhibited significant antioxidant activity in cells, C. elegans, and hyperlipidemic mice. Transcriptome analysis of mouse livers showed that the expression of plin5 was upregulated in diabetic mice administered FLRB, thereby preventing the excessive production of free fatty acids (FFAs) and the subsequent generation of large amounts of reactive oxygen species (ROS). These studies lay the foundation for the application of rice bran fermentation products.

Protective effect of Broussonetia papyrifera leaf polysaccharides on intestinal integrity in a rat model of diet-induced oxidative stress

This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1β and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death.

The effect of Melissa officinalis on diet-induced hyperlipidemia, hypercholesterolemia, oxidative stress and inflammation

The Lamiaceae family is an essential medicinal plant family. Melissa officinalis L. is a well-known medicinal plant of Lamiaceae. It was aimed to investigate the effects of Melissa officinalis infusion given to rats with hyperlipidemia and hypercholesterolemia in this study. It is seen that the high-fat diet (HFD) group causes weight gain from the third week. VLDL, LDL, HDL and cholesterol levels were found statistically significant differences (p˂0.05), fed a cholesterol-enriched high-fat diet group (HFD) compared to the control. It is seen that the cholesterol level of the high-fat diet+Melissa officinalis infusion (HFD+MOI) group was statistically significantly (p˂0.05). lower than the HFD group. In addition, the group in which Melissa officinalis was applied had positive effects on the antioxidant system and reduced the total oxidant system. The fact that the IFN-γ level of the HFD group was higher than the control indicates that the diet may have an inflammatory effect. As a result, HFD application with cholesterol caused hyperlipidemia and hypercholesterolemia in rats. The cholesterol-lowering effect of Melissa officinalis is observed. Remarkably, Melissa officinalis did not alter serum calcium levels while lowering cholesterol. In addition, it can said that HFD has a strengthening effect on the antioxidant system on oxidative stress.

A mechanistic exploration of the metabolome of African mango seeds and its potential to alleviate cognitive impairment induced by high-fat/high-carbohydrate diets: Involvement of PI3K/AKT/GSK-3β/CREB, PERK/CHOP/Bcl-2, and AMPK/SIRT-1/mTOR Axes.

Ethnopharmacological relevanceIrvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill., also known as “African mango” or “bush mango”, belonging to family Irvingiaceae, has been mostly used as food and traditional medicine for weight loss and to enhance the health. Aim of the studyThe overconsumption of high-fat and high-carbohydrate (HFHC) food induces oxidative stress, leading to neurological and cognitive dysfunction. Consequently, there is an immediate need for effective treatment. Hence, this study explored the efficacy of orlistat, metformin, and I. gabonensis seeds' total aqueous extract (IG SAE) in addressing HFHC-induced cognitive impairment by mitigating oxidative stress and their underlying mechanistic pathways. Materials and methodsInitially, the secondary metabolite profile of IG SAE is determined using high-performance liquid chromatography coupled with a mass detector (UHPLC/MS). The in vivo study involves two phases: an established model phase with control (10 rats on a standard diet) and HFHC diet group (50 rats) for 3 months. In the study phase, HFHC is divided into 5 groups. The first subgroup receives HFHC diet only, while the remaining groups each receive HFHC diet with either Orlistat, metformin, or IG SAE at doses of 100 mg/kg and 200 mg/kg, respectively, for 28 days. ResultsMore than 150 phytoconstituents were characterized for the first holistic approach onto IG metabolome. Characterization of IG SAE revealed that tannins dominate metabolites in the plant. Total phenolics and flavonoids were estimated to standardize our extract (77.12 ± 7.09 μg Gallic acid equivalent/mg extract and 8.039 ± 0.53 μg Rutin equivalent/mg extract, respectively).Orlistat, metformin, and IG SAE successfully reduced the body weight, blood glucose level, lipid profile, oxidative stress and neurotransmitters levels leading to improved behavioral functions as well as histological alternation. Also, IG SAE halted inflammation, apoptosis, and endoplasmic reticulum stress, together with promoting autophagy, via modulation of PI3K/AKT/GSK-3β/CREB, PERK/CHOP/Bcl-2 and AMPK/SIRT-1/m-TOR pathways. ConclusionMetformin, orlistat, and IG SAE offer a promising multi-target therapy to mitigate HFHC diet-induced oxidative stress, addressing cognitive function. This involves diverse molecular mechanisms, particularly the modulation of inflammation, ER stress, and both PI3K/AKT/GSK-3β/CREB and AMPK/SIRT-1/m-TOR pathways. Furthermore, the higher dose of IG SAE demonstrated effects comparable to orlistat and metformin across most studied parameters.

Rhythm and ROS: Hepatic Chronotherapeutic Features of Grape Seed Proanthocyanidin Extract Treatment in Cafeteria Diet-Fed Rats.

Polyphenols play a key role in the modulation of circadian rhythms, while the cafeteria diet (CAF) is able to perturb the hepatic biological rhythm and induce important ROS production. Consequently, we aimed to elucidate whether grape seed proanthocyanidin extract (GSPE) administration recovers the CAF-induced hepatic antioxidant (AOX) misalignment and characterize the chronotherapeutic properties of GSPE. For this purpose, Fischer 344 rats were fed a standard diet (STD) or a CAF and concomitantly treated with GSPE at two time-points (ZT0 vs. ZT12). Animals were euthanized every 6 h and the diurnal rhythms of hepatic ROS-related biomarkers, hepatic metabolites, and AOX gene expression were examined. Interestingly, GSPE treatment was able to recover the diurnal rhythm lost due to the CAF. Moreover, GSPE treatment also increased the acrophase of Sod1, as well as bringing the peak closer to that of the STD group. GSPE also corrected some hepatic metabolites altered by the CAF. Importantly, the differences observed at ZT0 vs. ZT12 due to the time of GSPE administration highlight a chronotherapeutic profile on the proanthocyanin effect. Finally, GSPE could also reduce diet-induced hepatic oxidative stress not only by its ROS-scavenging properties but also by retraining the circadian rhythm of AOX enzymes.

The impact of high-fat diet-induced oxidative stress on micro RNA’s in various tissues

Stress is the body’s reaction to any kind of injury or danger. It is linked to the production of oxidative free radicals, which are responsible for a variety of acute, chronic, and potentially fatal illnesses and diseases. Free radicals, due to their extreme reactivity, can harm or even kill cells. A High-Fat Diet (HFD) causes “oxidative stress”, which is characterized by an increase in the body’s generation of Reactive Oxygen Species (ROS) as a result of higher levels of triglycerides and Free Fatty Acids (FFA). HFD-induced oxidative stress alters cellular function by affecting transcriptional factors and mitochondrial enzymes (synthesis/inhibition). ROS and FFA damage the receptors of the epithelium, resulting in epithelial damage that impairs cellular function. ROS levels can harm cells by altering the expression of microRNA (miRNA), a sign of RNA damage. MiRNAs are non-coding RNAs found in animals, plants, and some viruses that play a role in the post-transcriptional regulation of gene expression. These three pathways—RNA cleavage, RNA destabilization, and RNA translation into proteins— all play a role in mRNA expression. The miRNA regulates the up- and downregulation of mRNA expression for cellular function, enzyme synthesis, and receptor modulation. MiRNA regulates cell function by maintaining the balance between cellular ROS levels and cellular damage.

Beneficial Effects of Viable and Heat-Inactivated Lactobacillus rhamnosus GG Administration on Oxidative Stress and Inflammation in Diet-Induced NAFLD in Rats

Oxidative stress and inflammation are well-known triggers of NAFLD onset and progression. The aim of this study is to compare the potential benefits of a viable probiotic (Lactobacillus rhamnosus GG) and its parabiotic (heat-inactivated) on oxidative stress, inflammation, DNA damage and cell death pathways in the liver of rats featuring diet-induced NAFLD. The consumption of the steatotic diet led to increased final body and liver weights, higher hepatic triacylglycerol content, altered serum transaminase levels and enhanced oxidative and inflammatory status. Administration of the probiotic and the parabiotic partially prevented the body weight increase induced by the steatotic diet, whereas the probiotic caused more effective decreasing hepatic triglyceride content. Sharp but nonstatistically significant decreases in serum transaminase levels were also observed for both treatments. The reduction in antioxidant enzyme activities found in the nontreated animals fed the steatotic diet was partially prevented by both treatments (GPx activity). Similarly, the reductions in nonenzymatic antioxidant protection (GSH content) and total antioxidant capacity (ORAC) found in the nontreated rats were restored by the administration of both treatments. These results show that both viable and heat-inactivated Lactobacillus rhamnosus GG administration partially prevent steatotic diet-induced liver oxidative stress and inflammation induced in rats.