scholarly journals Dietary Purple Potato Supplementation Ameliorates Gut Inflammation and Associated Colitis

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 535-535
Author(s):  
Shima Bibi ◽  
Yansong Xue ◽  
Yang He ◽  
Min Du ◽  
Boon Chew ◽  
...  
Keyword(s):  
Control Diet ◽  
Goblet Cells ◽  
Protective Effects ◽  
Mice Model ◽  
Differentiation Markers ◽  
Beneficial Effects ◽  
Funding Sources ◽  
Epithelial Structure ◽  
Biochemical Analyses ◽  
Deficient Mice

Abstract Objectives The incidence of inflammatory bowel disease (IBD) is rapidly increasing worldwide. Patients with IBD experience increased susceptibility to colorectal cancer and are associated with morbidity and mortality. Diets are known factors associated with IBD. This study examined the beneficial effects of dietary purple potato against spontaneous colitis and improving gut microbiota in interleukin (IL)-10-deficient mice, a commonly used IBD mice model. Methods IL-10-deficient mice at 7-week-old were assigned to a standard rodent diet (CON) or a control diet supplemented with 10% purple potato (dry feed weight) for 11 weeks, when colonic tissues were collected for histological and biochemical analyses. Results Purple potato supplementation had no effect on feed intake and body weight in IL-10-deficient mice during the 11-week feeding trial. Purple potato supplementation improved the colitis symptom and the integrity of the colonic epithelial structure with reduced inflammation and pathological scores. Furthermore, the density of goblet cells and differentiation markers for goblet cells was enhanced due to PP supplementation. Conclusions Data collectively showed that dietary purple potato supplementation had protective effects against colitis onset in IL-10-deficient mice and improved gut epithelial structure, providing a promising dietary approach for the management and prevention of colitis. Funding Sources USDA-NIFA and Northwest Potato Research Consortium.

scholarly journals The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice

2019 ◽  
Author(s):  
Agnes Wilhelmina Boots ◽  
Carmen Veith ◽  
Catrin Albrecht ◽  
Roger Bartholome ◽  
Marie Jose Drittij ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Levels ◽  
Control Diet ◽  
Redox Balance ◽  
Current Therapy ◽  
Inflammatory Lesions ◽  
Beneficial Effects ◽  
Dietary Antioxidant ◽  
Pulmonary Damage ◽  
Deficient Mice

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of unknown etiology. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Quercetin is a dietary antioxidant with strong redox modulating capacities suggested to exert part of its antioxidative effects via activation of the redox-sensitive transcription factor Nrf2. Therefore, the aim of the present study was to investigate if quercetin can exert anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrogenesis through Nrf2-dependent restoration of redox imbalance. Methods Homozygous Nrf2 deficient mice and their wildtype littermates were fed a control diet without or with 800 mg/kg quercetin from 7 days prior to a single 1 µg/2µl per g BW bleomycin challenge until they were sacrificed 14 days afterwards. Lung tissue and plasma were collected to determine markers of fibrosis (expression of extracellular matrix genes and histopathology), inflammation (pulmonary gene expression and plasma levels of Tumor Necrosis Factor-α (TNFα) and Keratinocyte Chemoattrachtant (KC)), and redox balance (pulmonary gene expression of antioxidants and malondialdehyde-dG (MDA)- DNA adducts). Results Mice fed the enriched diet had significantly enhanced plasma and pulmonary quercetin levels (11.08 ± 0.73 µM versus 7.05 ± 0.2 µM) combined with increased pulmonary expression of Nrf2 and Nrf2-responsive genes compared to mice fed the control diet. Upon bleomycin treatment, quercetin-fed mice displayed reduced expression of collagen (COL1A2) and fibronectin (FN1) and a tendency of reduced inflammatory lesions (2.8 ± 0.7 versus 1.9 ± 0.8). These beneficial effects were accompanied by reduced pulmonary gene expression of TNFα and KC, but not their plasma levels, and enhanced Nrf2-induced pulmonary antioxidant defences. In Nrf2 deficient mice, no effect of the dietary antioxidant on either histology or inflammatory lesions was observed. Conclusion Quercetin exerts anti-fibrogenic and anti-inflammatory effects on bleomycin-induced pulmonary damage in mice possibly through modulation of the redox balance by inducing Nrf2. However, quercetin could not rescue the bleomycin-induced pulmonary damage indicating that quercetin alone cannot ameliorate the progression of IPF.

scholarly journals Adherence to Mediterranean Style Dietary Pattern and Total Cancer Risk in the Framingham Offspring Cohort Study (P05-040-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ioanna Yiannakou ◽  
Martha Singer ◽  
Paul Jacques ◽  
Lynn Moore
Keyword(s):  
Cohort Study ◽  
Cancer Risk ◽  
Dietary Pattern ◽  
Protective Effects ◽  
Men And Women ◽  
Beneficial Effects ◽  
Funding Sources ◽  
Total Cancer Risk ◽  
Total Cancer ◽  
Former Smokers

Abstract Objectives This study examines the prospective association between adherence to a Mediterranean style dietary pattern and cancer risk among men and women in the Framingham Offspring (FOS) cohort. Methods The Mediterranean style dietary pattern (MSDP) score was derived from a semi-quantitative food frequency questionnaire taken at examination visit 5 in the prospective FOS cohort. Subjects included 3199 participants (1703 women and 1496 men), aged 30 years old and older, who were free of prevalent cancer. The MSDP score was classified into tertiles and also dichotomized (MSDP score <22 vs. ≥22) used to evaluate the association between the MSDP and cancer risk through the ninth examination cycle. Cox proportional-hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for confounding by age, physical activity, body mass Index, and pack-years of cigarette smoking. Factors found not to confound the effects of the MSDP were excluded from final models. Results During a mean follow-up of approximately 11.5 years, 377 and 273 cancer cases were documented among men and women, respectively. Women in the upper two tertiles of the MSDP score had a 25–30% lower cancer risks than women in the lowest tertile [(HR: 0.70, 95% CI:0.52–0.96 (tertile 2); HR, 0.75; 95% CI:0.56–1.00 (tertile 3)]. Effects in men were weaker [HR: 0.94, 95% CI:0.74–1.21 (tertile 2); HR, 0.90; 95% CI:0.68–1.17(tertile 3)]. The protective effects of higher MSDP adherence were stronger among non-smokers and former smokers than among current smokers. Compared with current smokers with a MSDP score < 22, non-smokers and former smokers with higher MSDP scores had approximately 43% and 39% reductions in total cancer risk, respectively (HR: 0.57; 95% CI: 0.43–0.75 for non-smokers with high MSDP; HR: 0.61; 95% CI: 0.47–0.79 for former smokers with high MSDP scores).SDP scores). Conclusions In this large cohort study, higher adherence to MSDP was associated with reduced risk of total cancer, especially among women. Beneficial effects of the MSDP were also stronger among non-smokers and former smokers. Funding Sources N/A.

scholarly journals Citrus Flavanone Naringenin Induces Browning and Brown Adipogenesis: Role of PPARgamma

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 382-382
Author(s):  
Yang Yang ◽  
Xinyun Xu ◽  
Haley Overby ◽  
Kelsey Hildreth ◽  
Ling Zhao
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Cell Lines ◽  
Differentiation Markers ◽  
Beneficial Effects ◽  
Funding Sources ◽  
White Adipocytes ◽  
Oil Red O ◽  
Brown Adipogenesis

Abstract Objectives Browning of white adipose tissue and brown adipogenesis induced by PPARg agonists have shown beneficial effects on obesity and associated metabolic disorders. Naringenin, a citrus flavanone, is a promising nutrient for obesity prevention partially through PPARg activation. We previously reported that naringenin significantly enhanced the isoproterenol (ISO)-stimulated thermogenesis by upregulating Ucp1 and Pgc1α in 3T3-L1 cell lines (murine white adipocytes). However, the effects of naringenin on browning and brown adipogenesis and its mechanisms have not been fully explored. We aim to investigate the effects of naringenin on browning and brown adipogenesis and its potential mechanisms in vitro. Methods Murine primary stromal white preadipocytes and murine brown preadipocytes were treated with 10 microM naringenin. PPARg knockdown (PPARg-KD) and scrambled nontargeting control (SCR) in 3T3-L1 cell lines and murine brown preadipocytes were generated and treated with naringenin (10 microM). Oil red o staining was performed to quantify lipid accumulation corresponding to the level of differentiation and the brown adipogenesis. mRNA and protein expression of candidate genes involved in thermogenesis and differentiation were analyzed by qRT-PCR and western blot, respectively. Results In murine primary stromal white adipocytes, naringenin significantly increased Ucp1 mRNA expression at the basal state and significantly enhanced the ISO-stimulated upregulation of Ucp1 and Pgc1α mRNA expression. PPARg-KD significantly blocked the naringenin-induced upregulation of Ucp1 and Pgc1α mRNA. In addition, naringenin significantly promoted the differentiation of brown preadipocytes as determined by oil red o lipid staining. Consistently, protein expression of general differentiation markers including FABP4, HSL, PLIN, and ATGL and thermogenic markers UCP1 and PGC1 α were significantly increased by naringenin, which was significantly attenuated by PPARg knockdown. Conclusions Combined with our previous study showing that naringenin transactivated PPARg using reporter assays, we demonstrated that naringenin induced browning of primary stromal white adipocytes and promoted brown adipogenesis through PPARg activation. Funding Sources The work was supported by funding from NIH.

Application of mycotoxin adsorbent to cattle feed contaminated with zearalenone: urinary zearalenone excretion and association with anti-Müllerian hormone

2014 ◽  
Vol 7 (3) ◽  
pp. 367-378 ◽  
Author(s):  
Y. Fushimi ◽  
M. Takagi ◽  
H. Hasunuma ◽  
S. Uno ◽  
E. Kokushi ◽  
...  
Keyword(s):  
Sampling Period ◽  
Antral Follicle ◽  
Positive Control ◽  
Control Group ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Biochemical Analyses ◽  
Mycotoxin Adsorbent ◽  
Female Cattle

This study investigated (1) protective effects of a commercially available mycotoxin adsorbent (MA) and (2) endocrine effects of in vivo exposure to zearalenone (ZEA) in cattle. The sample included a Japanese Black female cattle herd (MYT herd) that displayed persistently high urinary ZEA concentrations. A second herd (NM herd) was used as a control. Three groups from each herd were assessed: MX (n=6; MA mixed with concentrate), TD (n=6; MA applied as topdressing with the concentrate), and a positive control (n=6; no MA application). Urine and blood samples were collected at the start of MA supplementation (day 0), on the final day of supplementation (day 16), and on the final day of the sampling period (day 58 for MYT herd and day 50 for NM herd). Urinary ZEA concentrations (pg/mg of creatinine) were measured by ELISA and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Haematological and serum biochemical analyses were performed to monitor hepatic, renal, nutritional, and mineral intake statuses. Ovulation status was assessed by progesterone (P4) and antral follicle population by anti-Müllerian hormone (AMH) levels. The urinary concentrations of ZEA and its metabolites in the MX and TD groups were significantly lower (P<0.05) at day 16 compared with the control group, as measured by LC-MS/MS. The valid ratio of AMH-positive (≯0.08 ng/ml) cattle was significantly higher in the NM herd than in the MYT herd without affecting the P4-positive (≯3 ng/ml) ratio, suggesting different populations of antral follicles. Significant differences were also observed between the MX and the control in aspartate aminotransferase and γ-glutamyltransferase at day 58, suggesting preventive effects of MA supplementation. Our field trial indicated that MA supplementation of a ZEA-contaminated diet has beneficial effects in reducing ZEA absorption from the intestine of cattle, maintaining endocrine homeostasis and reversing hepatic effects.

scholarly journals Sulforaphane Protects Against DSS-Induced Acute Colitis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 481-481
Author(s):  
Qiyu Tian ◽  
Min Du ◽  
Xhixin Xu ◽  
Mei-Jun Zhu
Keyword(s):  
Activity Index ◽  
Inflammatory Marker ◽  
Control Diet ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Ampk Signaling ◽  
Epithelial Regeneration ◽  
Epithelial Structure

Abstract Objectives This study tested the hypothesis that sulforaphane (SFN) enhances intestinal integrity and epithelial regeneration via AMPK/Nrf2 activation. Methods Male mice at 8-wk-old were subjected to control diet (CON) or CON with 600 ppm SFN for 4 weeks, and then half of mice within each dietary group were subjected to colitis induction (9-day-2.5% DSS treatment in drinking plus 9-day-recovery), while remaining their respective diet. Results SFN administration alleviated acute DSS-induced body weight loss and reduced disease activity index (DAI) score, as well as colon shortening in DSS-treated mice. Additionally, SFN supplementation decreased the mRNA expression of inflammatory markers, interleukin (IL)-1β, while increased anti-inflammatory marker IL-10 in DSS-challenged mice. Furthermore, SFN protected colonic epithelial structure, which was associated with activated AMPK signaling, increased Nrf2 and heme oxygenase-1 content in DSS-induced colitis mice. The roles of AMPK/Nrf2 signaling in mediating the improvement of gut epithelial regeneration following DSS-induced injury will be further studied. Conclusions SFN supplementation had protective effects against DSSinduced colitis and improved gut epithelial structure, which was associated with activation of AMPK/NrF2 signaling. Dietary SFN is a promising approach for the management and prevention of colitis. Funding Sources USDA-NIFA 2018-67,017-27,517.

scholarly journals Contribution of Carbohydrates and Polyphenols to Dried Plum's Prebiotic Activity (P20-029-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kendall Anderson ◽  
Bryant Keirns ◽  
Babajide Ojo ◽  
Karley Washburn ◽  
Jennifer Graef ◽  
...  
Keyword(s):  
Body Composition ◽  
Weight Gain ◽  
Control Diet ◽  
Short Chain Fatty Acids ◽  
Hormone Deficiency ◽  
Protective Effects ◽  
Mineral Density ◽  
Time Points ◽  
Funding Sources ◽  
Β Diversity

Abstract Objectives In addition to bone protective effects, dried plums (DP) also prevent weight gain in animal models of ovarian hormone deficiency. The aim of this project was to investigate the contribution of the polyphenol (PP) and carbohydrate (CHO) components of DP on weight gain and body composition, as well as their effects on the gut environment. Methods Two studies were performed using 8-wk-old C57BL/6 female mice that were sham-operated (Sham) or ovariectomized (Ovx), and allowed to lose bone prior to treatment for 5 or 10 wks. In Study 1, Sham and Ovx mice were assigned to control (AIN-93 M), control diet with added DP (25% w/w) or a crude PP extract (CPE; equivalent PP to DP). In Study 2, Ovx mice were randomized to diets with the CPE fractions, PP or CHO, in a 2x2 factorial design. At the end of each study, bone mineral density (BMD) and body composition were assessed. Cecal bacterial taxa and short chain fatty acids (SCFA) were characterized at 5 and 10 wks, respectively. Non-microbiome data were analyzed using 1-way or 2-way ANOVA (SAS, Version 9.4). Results In Study 1, Ovx increased (P < 0.01) weight gain, %fat and abdominal white adipose tissue (WAT), and DP and CPE mitigated (P < 0.05) this response at 5 and 10 wks. Likewise, DP and CPE reversed the Ovx-induced decrease in BMD at both time points. DP and CPE enriched the SCFA-producing family, Lachnospiraceae, as well as Coriobacteriaceae and Verrucomicrobiaceae, which are associated with weight regulation. Cecal acetic, propionic, n-butyric and n-valeric acids were increased by DP and CPE compared to Ovx-control, but the response was greater with DP. In Study 2, CHO with or without PP, reduced Ovx-induced weight gain (P < 0.01), %fat (P < 0.001), WAT (P < 0.01) and reversed the loss of BMD at both time points. Compared to CPE, Verrucomicrobiaceae was more abundant with the PP group, but there was no change in β diversity with the CHO group. All of the assessed SCFA were increased with CHO, regardless of PP content, while n-butyric acid and the two isomers of valeric acid were independently enhanced by PP. Among the assessed outcomes, there were no additive effects of CHO and PP. Conclusions Although their prebiotic effects differ, both the CHO and PP components contribute to DP's effects on weight gain and body composition. Funding Sources OCAST; California Dried Plum Board.

scholarly journals The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice

2020 ◽  
Author(s):  
Agnes Wilhelmina Boots ◽  
Carmen Veith ◽  
Catrin Albrecht ◽  
Roger Bartholome ◽  
Marie Jose Drittij ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Levels ◽  
Control Diet ◽  
Redox Balance ◽  
Current Therapy ◽  
Inflammatory Lesions ◽  
Beneficial Effects ◽  
Dietary Antioxidant ◽  
Pulmonary Damage ◽  
Deficient Mice

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of unknown etiology. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Quercetin is a dietary antioxidant with strong redox modulating capacities suggested to exert part of its antioxidative effects via activation of the redox-sensitive transcription factor Nrf2. Therefore, the aim of the present study was to investigate if quercetin can exert anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrogenesis through Nrf2-dependent restoration of redox imbalance. Methods Homozygous Nrf2 deficient mice and their wildtype littermates were fed a control diet without or with 800 mg/kg quercetin from 7 days prior to a single 1 µg/2µl per g BW bleomycin challenge until they were sacrificed 14 days afterwards. Lung tissue and plasma were collected to determine markers of fibrosis (expression of extracellular matrix genes and histopathology), inflammation (pulmonary gene expression and plasma levels of Tumor Necrosis Factor-α (TNFα) and Keratinocyte Chemoattrachtant (KC)), and redox balance (pulmonary gene expression of antioxidants and malondialdehyde-dG (MDA)- DNA adducts). Results Mice fed the enriched diet had significantly enhanced plasma and pulmonary quercetin levels (11.08 ± 0.73 µM versus 7.05 ± 0.2 µM) combined with increased pulmonary expression of Nrf2 and Nrf2-responsive genes compared to mice fed the control diet. Upon bleomycin treatment, quercetin-fed mice displayed reduced expression of collagen (COL1A2) and fibronectin (FN1) and a tendency of reduced inflammatory lesions (2.8 ± 0.7 versus 1.9 ± 0.8). These beneficial effects were accompanied by reduced pulmonary gene expression of TNFα and KC, but not their plasma levels, and enhanced Nrf2-induced pulmonary antioxidant defences. In Nrf2 deficient mice, no effect of the dietary antioxidant on either histology or inflammatory lesions was observed. Conclusion Quercetin exerts anti-fibrogenic and anti-inflammatory effects on bleomycin-induced pulmonary damage in mice possibly through modulation of the redox balance by inducing Nrf2. However, quercetin could not rescue the bleomycin-induced pulmonary damage indicating that quercetin alone cannot ameliorate the progression of IPF.

Gut-liver axis modulation in fructose-fed mice: a role for PPAR-alpha and linagliptin

2020 ◽  
Vol 247 (1) ◽  
pp. 11-24
Author(s):  
Flávia Maria Silva-Veiga ◽  
Carolline Santos Miranda ◽  
Fabiane Ferreira Martins ◽  
Julio Beltrame Daleprane ◽  
Carlos Alberto Mandarim-de-Lacerda ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Glucose Intolerance ◽  
Control Diet ◽  
Intestinal Barrier ◽  
Mice Model ◽  
Ppar Alpha ◽  
Beneficial Effects ◽  
Hepatic Energy Metabolism ◽  
High Fructose ◽  
Alpha Agonist

Fructose dietary intake affects the composition of the intestinal microbiota and influences the development of hepatic steatosis. Endotoxins produced by gram-negative bacteria alter intestinal permeability and cause bacterial translocation. This study evaluated the effects of gut microbiota modulation by a purified PPAR-alpha agonist (WY14643), a DPP-4 inhibitor (linagliptin), or their association on intestinal barrier integrity, endotoxemia, and hepatic energy metabolism in high-fructose-fed C57BL/6 mice. Fifty mice were divided to receive the control diet (C group) or the high-fructose diet (HFRU) for 12 weeks. Subsequently, the HFRU group was divided to initiate the treatment with PPAR-alpha agonist (3.5 mg/kg/BM) and DPP-4 inhibitor (15 mg/kg/BM). The HFRU group had glucose intolerance, endotoxemia, and dysbiosis (with increased Proteobacteria) without changes in body mass in comparison with the C group. HFRU group showed damaged intestinal ultrastructure, which led to liver inflammation and marked hepatic steatosis in the HFRU group when compared to the C group. PPAR-alpha activation and DPP-4 inhibition countered glucose intolerance, endotoxemia, and dysbiosis, ameliorating the ultrastructure of the intestinal barrier and reducing Tlr4 expression in the liver of treated animals. These beneficial effects suppressed lipogenesis and mitigated hepatic steatosis. In conclusion, the results herein propose a role for PPAR-alpha activation, DPP-4 inhibition, and their association in attenuating hepatic steatosis by gut-liver axis modulation in high-fructose mice model. These observations suggest these treatments as potential targets to treat hepatic steatosis and avoid its progression.

scholarly journals Dietary DHA: time course of tissue uptake and effects on cytokine secretion in mice

2010 ◽  
Vol 104 (9) ◽  
pp. 1304-1312 ◽  
Author(s):  
Jennifer Lefils ◽  
Alain Géloën ◽  
Hubert Vidal ◽  
Michel Lagarde ◽  
Nathalie Bernoud-Hubac
Keyword(s):  
Washout Period ◽  
Time Course ◽  
Control Diet ◽  
Protective Effects ◽  
Tissue Uptake ◽  
Adiponectin Concentration ◽  
Adipose Tissues ◽  
Beneficial Effects ◽  
Mouse Tissues ◽  
Plasma Leptin

Consumption of DHA has numerous beneficial effects, but little is known about these effects during the first few days of the DHA dietary intake. The main objectives of the present study were to determine the time course of DHA incorporation into phospholipids in different mouse tissues and the effects of DHA supplementation on adiponectin and leptin secretion. Mice were fed either a control diet or a DHA-rich diet, and some were killed on days 0, 4, 8, 16 and 32. Some mice were fed the DHA-rich diet for 16 d, and were then maintained on the control diet for sixteen more days (washout period). DHA supplementation increased plasma adiponectin secretion by 2·4-fold as early as 4 d after the initiation of the DHA-rich diet feeding. The adiponectin concentration remained 1·6-fold higher after the 16 d washout period. Plasma leptin levels were significantly lower after 4 d of feeding with DHA. These effects were associated with a significant increase in DHA incorporation in phosphatidylethanolamine and phosphatidylcholine of all analysed tissues (liver, heart and white adipose tissues). DHA mainly got incorporated at the expense of n-6 arachidonic acid. The present data show that DHA rapidly improved the profile of secreted adipokines, and that these protective effects were long lasting.

scholarly journals The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice

2020 ◽  
Author(s):  
Agnes Wilhelmina Boots ◽  
Carmen Veith ◽  
Catrin Albrecht ◽  
Roger Bartholome ◽  
Marie Jose Drittij ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Tissue ◽  
Plasma Levels ◽  
Control Diet ◽  
Redox Balance ◽  
Inflammatory Lesions ◽  
Beneficial Effects ◽  
Dietary Antioxidant ◽  
Pulmonary Damage ◽  
Deficient Mice

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of which the etiology is still not fully understood. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Quercetin is a dietary antioxidant with strong redox modulating capacities that is suggested to exert part of its antioxidative effects via activation of the redox-sensitive transcription factor Nrf2 that regulates endogenous antioxidant levels. Therefore, the aim of the present study was to investigate if the dietary antioxidant quercetin can exert anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrogenesis through Nrf2-dependent restoration of redox imbalance. Methods Homozygous Nrf2 deficient mice and their wildtype littermates were fed a control diet without or with 800 mg quercetin per kg diet from 7 days prior to a single 1 µg/2µl per g BW bleomycin challenge until they were sacrificed 14 days afterwards. Lung tissue and plasma were collected to determine markers of fibrosis (expression of extracellular matrix genes and histopathology), inflammation (pulmonary gene expression and plasma levels of Tumor Necrosis Factor-α (TNFα) and Keratinocyte Chemoattrachtant (KC)), and redox balance (pulmonary gene expression of antioxidants and malondialdehyde-dG (MDA)- DNA adducts). Results Mice fed the enriched diet for 7 days prior to the bleomycin challenge had significantly enhanced plasma and pulmonary quercetin levels (11.08 ± 0.73 µM versus 7.05 ± 0.2 µM) combined with increased expression of Nrf2 and Nrf2-responsive genes compared to mice fed the control diet in lung tissue. Upon bleomycin treatment, quercetin-fed mice displayed reduced expression of collagen (COL1A2) and fibronectin (FN1) and a tendency of reduced inflammatory lesions (2.8 ± 0.7 versus 1.9 ± 0.8). These beneficial effects were accompanied by reduced pulmonary gene expression of TNFα and KC, but not their plasma levels, and enhanced Nrf2-induced pulmonary antioxidant defences. In Nrf2 deficient mice, no effect of the dietary antioxidant on either histology or inflammatory lesions was observed. Conclusion Quercetin exerts anti-fibrogenic and anti-inflammatory effects on bleomycin-induced pulmonary damage in mice possibly through modulation of the redox balance by inducing Nrf2. However, quercetin could not rescue the bleomycin-induced pulmonary damage indicating that quercetin alone cannot ameliorate the progression of IPF.

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