Quercetin inhibits the cytotoxicity and oxidative stress in liver of rats fed aflatoxin-contaminated diet.
ABSTRACT: This study was conducted to evaluate the protective role of quercetin (Q) against the cytotoxicity, DNA damage and oxidative stress in rats fed aflatoxin (AFs)-contaminated diet. Female Sprague-Dawley rats were divided into six groups and treated for 21 days as follows: the control group; the group fed AFs-contaminated diet (1.4 mg/kg diet); the groups treated orally with Q at low or high dose (50 and 100 mg/kg b.w.) and the groups AFs-contaminated diet plus low or high dose of Q. At the end of experiment, blood and liver samples were collected for biochemical, histological, histochemical and genetic analyses. The results indicated that animal fed AFs-contaminated diet showed significant increase in serum biochemical parameters, oxidative stress markers and DNA fragmentation accompanied with significant decrease in total proteins, GPX, SOD, DNA and RNA content and fatty acid synthase (Fas) and TNF? gene expression in the liver tissue. Q at the two tested doses succeeded to normalize the biochemical parameters, improved the content of nucleic acids in hepatic tissues, the gene expression, the histopathological and histochemical picture of the liver. It could be concluded that Q has a potential antioxidant activity, a protective action and regulated the alteration of genes expression induced by AFs.
Project description:Mushrooms have been used in folk medicine for thousands of years. In this study, the effect of ? -glucan-rich extract of P. sajor-caju (GE) on lipid lowering and antioxidant potential was assessed in C57BL/6J mice fed on a high-fat diet. Obesity was induced in C57BL/6J mice by feeding a high-fat diet. The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240?mg/kg b.w) and HFD60, HFD120, and HFD240 (for high-fat diet), where the mice were administrated with three dosages of GE (60, 120, and 240?mg GE/kg b.w). Metformin (2?mg/kg b.w) served as positive control. GE-treated groups showed significantly reduced body weight, serum lipid, and liver enzymes levels. GE also attenuated protein carbonyl and lipid hydroperoxide levels by increasing the enzymic antioxidants (SOD, CAT, and GPx) activities in the mice. GE-treated groups induced the expression of hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) while downregulated the expression of peroxisome proliferator-activated receptor gamma (PPAR- ? ), sterol regulatory binding protein-1c (SREBP-1c), and lipoprotein lipase (LPL). Hence, GE prevented weight gain in the mice by inducing lipolysis and may be valuable in the formulation of adjuvant therapy for obesity.
Project description:Nonalcoholic fatty liver disease (NAFLD), a premorbid condition, lacks proper management owing to multitude of abnormalities. In this study, we compared the effects of a potent antioxidant, grape seed proanthocyanidins (GSP), and an insulin sensitizer, metformin (MET), in high-fat-fructose-diet- (HFFD-) induced albino Wistar rat model of NAFLD. Either GSP (100?mg/Kg b.w) or MET (50?mg/Kg b.w) or both were administered as therapeutic options. HFFD-fed rats showed abnormal plasma lipid profile, inflammation, and steatosis of the liver when examined by biochemical and histology techniques. Increased lipid storage, lipogenesis, and reduced lipolysis were evident from mRNA expression studies of hepatic lipid droplets (LD) proteins, sterol regulatory element binding 1c (SREBP 1c), and peroxisome proliferator activated receptor- ? (PPAR- ? ). GSP administration to HFFD-fed rats caused 69% reduction in hepatic TG levels, whereas MET caused only 23%. The combination treatment reduced TG levels by 63%. GSP reduced the mRNA expression of SREBP1c and LD proteins and increased that of PPAR- ? more effectively compared to MET in HFFD-induced hyperlipidemic rats. Combination of MET and GSP improved the metabolism of lipids effectively, but the effect was not additive in restoring lipid levels.
Project description:The aim of the present study was to examine the role of chronic deoxynivalenol (DON) exposition on the liver morphology and function in combination with pre- and post-hepatic lipopolysaccharide (LPS) stress in young pigs fed for 4 weeks with a DON-contaminated diet (4.59 mg/kg feed). At the end of the experiment, LPS (7.5 ?g/kg BW) was administered for 1 h pre-hepatically (Vena portae hepatis) or post-hepatically (Vena jugularis). Liver morphology was macroscopically checked and showed haemorrhage in all LPS groups, significantly higher relative liver weights, accompanied by marked oedema in the gallbladder wall. Histological changes were judged by a modified histology activity index (HAI). Liver HAI score was significantly increased in all LPS groups compared to placebo, primarily due to neutrophil infiltration and haemorrhage. DON feed alone was without effect on the liver HAI. Liver function was characterized by (i) hepatic biochemical markers, (ii) mitochondrial respiration and (iii) Ca2+ accumulation capacity of isolated mitochondria. Clinical chemical parameters characterizing liver function were initially (<3 h) slightly influenced by LPS. After 3 h, bilirubin and alkaline phosphatase were increased significantly, in DON-fed, jugular-infused LPS group. Respiration and Ca2+ accumulation capacity of isolated liver mitochondria was not impaired by chronic DON exposure, acute LPS challenge or combined treatments. DON-contaminated feed did not change macroscopy and histology of the liver, but modified the function under LPS stress. The different function was not linked to modifications of liver mitochondria.
Project description:<h4>Background and aim</h4><i>Saccharomyces cerevisiae</i>, bentonite and kaolin were used to reduce the adverse effects of mold-contaminated diet on broilers. The aim of the study was to evaluate the impact of <i>S. cerevisiae</i>, bentonite, and kaolin in reducing the adverse effects of mold (fungal) contaminated diet on broilers. Specifically, we investigated the histopathological, hematological, and serum biochemical changes associated with broilers fed mold-contaminated diets supplemented with these three adsorbents. We also isolated and identified the common fungal contaminants in the poultry feeds as well as the mycotoxins they produced.<h4>Materials and methods</h4>Hundred broilers (3-weeks-old) were randomly grouped into five dietary treatments, basal feed (negative control), feed contaminated with mold, mold-contaminated feed+<i>S. cerevisiae</i>, mold-contaminated feed+bentonite, and mold-contaminated feed+kaolin. The fungal contaminants in the feeds were isolated and molecularly identified while the mycotoxins in the feed where analyzed using high-performance liquid chromatography. Blood samples of birds from each group were analyzed for hematology and serum biochemistry. The liver, spleen, kidney, and bursa of Fabricius of the birds were excised and analyzed for histopathological changes.<h4>Results</h4>The most common fungal contaminants in the feeds were <i>Penicillium</i> (33.3%) species, followed by <i>Aspergillus</i> species (22.2%). The mold-contaminated feed had the highest number of fungal contaminants, 55.6%, while the negative control (basal feed group) had none. Total aflatoxin and deoxynivalenol were high in the mold-contaminated feed (53.272 ?g/kg and 634.5 ?g kg, respectively), but these were reduced by the addition of adsorbents to the feed. The birds fed mold-contaminated feed had significantly (p<0.05) reduced red blood cell count counts, packed cell volume, and hemoglobin but increased white blood cell count compared to the negative control. Liver enzyme activity (alanine transaminase, aspartate aminotransferase, and alkaline phosphatase) and cholesterol concentration increased significantly (p<0.05) in the group fed mold-contaminated feed while the serum albumin and total protein decreased significantly (p<i><</i>0.05) in comparison with the negative control. Adverse histopathological changes were observed in the liver, kidney, spleen, and bursa of Fabricius in the group fed mold-contaminated feed. Addition of <i>S. cerevisiae</i>, bentonite or kaolin in the mold-contaminated feed ameliorated these toxic effects.<h4>Conclusion</h4>The observed histopathological lesions were consistent with mycotoxicosis in birds and were mild in the adsorbent treated groups. Kaolin had a higher protective effect against mycotoxicosis than the two other adsorbents.
Project description:The purpose of this study was to investigate the potential of a byproduct mixture derived from grapeseed and sea buckthorn oil industry to mitigate the harmful damage produced by ochratoxin A and aflatoxin B1 at hepatic and renal level in piglets after weaning. Forty cross-bred TOPIGS-40 hybrid piglets after weaning were assigned to three experimental groups (E1, E2, E3) and one control group (C), and fed with experimental diets for 30 days. The basal diet was served as a control and contained normal compound feed for starter piglets without mycotoxins. The experimental groups were fed as follows: E1—basal diet plus a mixture (1:1) of two byproducts (grapeseed and sea buckthorn meal); E2—the basal diet experimentally contaminated with mycotoxins (479 ppb OTA and 62ppb AFB1); and E3—basal diet containing 5% of the mixture (1:1) of grapeseed and sea buckthorn meal and contaminated with the mix of OTA and AFB1. After 4 weeks, the animals were slaughtered, and tissue samples were taken from liver and kidney in order to perform gene expression and histological analysis. The gene expression analysis showed that when weaned piglets were fed with contaminated diet, the expression of most analyzed genes was downregulated. Among the CYP450 family, CYP1A2 was the gene with the highest downregulation. According to these results, in liver, we found that mycotoxins induced histomorphological alterations in liver and kidney and had an effect on the expression level of CYP1A2, CYP2A19, CYP2E1, and CYP3A29, but we did not detect important changes in the expression level of CY4A24, MRP2 and GSTA1 genes.
Project description:Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-? dependent. C57BL6 wild-type (WT) and PPAR-?-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300?mg/kg of b.w.) or PMA 300?mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-?; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF ????B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-?.
Project description:BACKGROUND:Even though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food. OBJECTIVE:The present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis. DESIGN:Rats were divided into four groups (n=6 per group) after 1 week of acclimatization: a normal diet group comprised rats fed the AIN76A rodent diet; a high-fat diet-induced obese group with rats fed a 60% high-fat diet; a Garcinia cambogia treated group (positive control) with rats fed a 60% high-fat diet with G. cambogia 500 g/kg body weight (b.w.)/day; and an fermented C. longa L. 50% ethanolic extract treated group (FCE50) with rats fed a 60% high-fat diet with FCE50 500 g/kg b.w./day. Each group received the appropriate vehicle or sample daily by gastric intubation for 12 weeks. RESULTS:We found that FCE50 administration suppressed b.w. gain and reduced white adipose tissue weight, serum triglyceride (TG), and cholesterol in high-fat diet-induced obese rats. These results can be associated with the suppression of adipocyte differentiation and lipogenesis with a decrease in the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, adipocyte protein 2, and lipoprotein lipase induced by FCE50 administration. In addition, FCE50 increased lipolysis and ?-oxidation by up-regulating the expression of lipases such as adipose triglyceride lipase, hormone-sensitive lipase, adiponectin, and AMP-activated protein kinase. CONCLUSIONS:These results suggest that FCE50 can be a candidate for the prevention of obesity via suppressing adipogenesis and promoting lipolysis.
Project description:PURPOSE:Aim of the study was to find out if gallic acid (GA), a common phenolic in plant foods, prevents obesity induced DNA damage which plays a key role in the induction of overweight associated cancer. METHODS:Male and female C57BL6/J mice were fed with a low fat or a high fat diet (HFD). The HFD group received different doses GA (0, 2.6-20 mg/kg b.w./day) in the drinking water for 1 week. Subsequently, alterations of the genetic stability in blood and inner organs were monitored in single cell gel electrophoresis assays. To elucidate the underlying molecular mechanisms: oxidized DNA bases, alterations of the redox status, lipid and glucose metabolism, cytokine levels and hepatic NF-κB activity were monitored. RESULTS:HFD fed animals had higher body weights; increased DNA damage and oxidation of DNA bases damage were detected in colon, liver and brain but not in blood and white adipose tissue. Furthermore, elevated concentrations of insulin, glucose, triglycerides, MCP-1, TNF-α and NF-κB activity were observed in this group. Small amounts of GA, in the range of human consumption, caused DNA protection and reduced oxidation of DNA bases, as well as biochemical and inflammatory parameters. CONCLUSIONS:Obese animals have increased DNA damage due to oxidation of DNA bases. This effect is probably caused by increased levels of glucose and insulin. The effects of GA can be explained by its hypoglycaemic properties and indicate that the consumption of GA-rich foods prevents adverse health effects in obese individuals.
Project description:Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD) or a control diet (CD) with and without vitamin E supplementation (4.5 mg/kg body weight (b.w.)) for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene (MLH1) were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1. Vitamin E reduced DNA damage and showed organ-specific effects on MLH1 and Dnmt1 gene expression and methylation. These results suggest that interventions with antioxidants and epigenetic active food ingredients should be developed as an effective prevention for obesity-and oxidative stress-induced health risks.
Project description:The present study was performed to evaluate the antioxidant and intestinal protective effects of baicalin-copper on deoxynivalenol-challenged piglets. Forty weaned piglets were randomly divided into four groups and assigned to different diets: (1) basal diet (Con), (2) 4?mg/kg deoxynivalenol of basal diet (DON), (3) 5?g/kg baicalin-copper of basal diet (BCU); and (4) 4?mg/kg?deoxynivalenol + 5?g/kg?baicalin-copper of basal diet (DBCU). The results showed that the ADFI and ADG of piglets in the DON group were markedly lower than those in the Con group, but the ADFI and ADG of the DBCU group were not significantly different from those of the Con group. In piglets fed a DON-contaminated diet, dietary supplementation with BCU significantly decreased the mRNA levels of P70S6K, 4E-BP1, and HSP70 in the liver, the protein expression of HO-1 in the jejunum, and the expression of p-Nrf2 and p-NF-?B in the ileum but increased Mn-SOD activity in serum. Dietary supplementation with BCU increased jejunal maltase, ZIP4 and MT mRNA levels, and serum concentrations of Arg, Val, Ile, Leu, Lys, and Tyr in DON-contaminated piglets. In summary, BCU can alleviate the growth impairment induced by DON and enhance antioxidant capacity and nutrition absorption in piglets fed DON-contaminated diets.