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A blueberry-enriched diet improves renal function and reduces oxidative stress in metabolic syndrome animals: potential mechanism of TLR4-MAPK signaling pathway.

Nair AR, Elks CM, Vila J, Del Piero F, Paulsen DB, Francis J - PLoS ONE (2014)

Bottom Line: Kidney redox status and urinary albumin levels were quantified.In addition, OZR had increased phosphorylation of ERK and p38MAPK.Blueberry-fed OZR exhibited significant improvements in all these parameters compared to OZR.

View Article: PubMed Central - PubMed

Affiliation: Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.

ABSTRACT

Background: Metabolic syndrome (MetS) is characterized by a cluster of health factors that indicate a higher risk for cardio-renal diseases. Recent evidence indicates that antioxidants from berries are alternative to attenuate oxidative stress and inflammation. We tested the hypothesis that inflammation-induced renal damage is triggered by the activation of TLR4, and subsequent modulation of redox-sensitive molecules and mitogen-activated protein kinase (MAPK) pathway.

Methods: Five-week old lean and obese Zucker rats (LZR and OZR) were fed a blueberry-enriched diet or an isocaloric control diet for 15 weeks. A glucose tolerance test and acute renal clearance experiments were performed. Gene and protein expression levels for TLR4, cytokines and phosphorylation of ERK and p38MAPK were measured. Kidney redox status and urinary albumin levels were quantified. Renal pathology was evaluated histologically.

Results: Control OZR exhibited lower glucose tolerance; exacerbated renal function parameters; increased oxidative stress. Gene and protein expression levels of TLR4 were higher and this was accompanied by increased renal pathology with extensive albuminuria and deterioration in antioxidant levels in OZR. In addition, OZR had increased phosphorylation of ERK and p38MAPK. Blueberry-fed OZR exhibited significant improvements in all these parameters compared to OZR.

Conclusion: TLR4-MAPK signaling pathway is a key to the renal structural injury and dysfunction in MetS and blueberry (BB) protect against this damage by inhibiting TLR4.

Significance: This is the first study to put forth a potential mechanism of TLR4-induced kidney damage in a model of MetS and to elucidate a downstream mechanism by which blueberry exert their reno-protective effects.

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Related in: MedlinePlus

Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.Renal cortical catalase (A) and SOD (B) levels as determined by commercially available kits (n = 6). (C) A representative western blot showing Nrf2 and Keap 1 protein expression. Western bands for Nrf2 (D) and Keap1 (E) were analyzed and quantified by densitometry. All values are presented as mean ± SEM (*p<0.05, **p<0.01, ***p<0.001).
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pone-0111976-g009: Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.Renal cortical catalase (A) and SOD (B) levels as determined by commercially available kits (n = 6). (C) A representative western blot showing Nrf2 and Keap 1 protein expression. Western bands for Nrf2 (D) and Keap1 (E) were analyzed and quantified by densitometry. All values are presented as mean ± SEM (*p<0.05, **p<0.01, ***p<0.001).

Mentions: We measured the cortical levels of the antioxidant enzymes SOD and catalase in all experimental groups (Figure 9A–9B). SOD catalyzes the conversion of superoxide into oxygen and hydrogen peroxide. Catalase breaks down hydrogen peroxide. The SOD and catalase levels were depleted in rats belonging to the OZRCC group compared to the LZR groups. A blueberry-enriched diet significantly increased the SOD and catalase levels in the OZRBB group, indicating a beneficial antioxidant effect of BB in MetS animals.


A blueberry-enriched diet improves renal function and reduces oxidative stress in metabolic syndrome animals: potential mechanism of TLR4-MAPK signaling pathway.

Nair AR, Elks CM, Vila J, Del Piero F, Paulsen DB, Francis J - PLoS ONE (2014)

Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.Renal cortical catalase (A) and SOD (B) levels as determined by commercially available kits (n = 6). (C) A representative western blot showing Nrf2 and Keap 1 protein expression. Western bands for Nrf2 (D) and Keap1 (E) were analyzed and quantified by densitometry. All values are presented as mean ± SEM (*p<0.05, **p<0.01, ***p<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221362&req=5

pone-0111976-g009: Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.Renal cortical catalase (A) and SOD (B) levels as determined by commercially available kits (n = 6). (C) A representative western blot showing Nrf2 and Keap 1 protein expression. Western bands for Nrf2 (D) and Keap1 (E) were analyzed and quantified by densitometry. All values are presented as mean ± SEM (*p<0.05, **p<0.01, ***p<0.001).
Mentions: We measured the cortical levels of the antioxidant enzymes SOD and catalase in all experimental groups (Figure 9A–9B). SOD catalyzes the conversion of superoxide into oxygen and hydrogen peroxide. Catalase breaks down hydrogen peroxide. The SOD and catalase levels were depleted in rats belonging to the OZRCC group compared to the LZR groups. A blueberry-enriched diet significantly increased the SOD and catalase levels in the OZRBB group, indicating a beneficial antioxidant effect of BB in MetS animals.

Bottom Line: Kidney redox status and urinary albumin levels were quantified.In addition, OZR had increased phosphorylation of ERK and p38MAPK.Blueberry-fed OZR exhibited significant improvements in all these parameters compared to OZR.

View Article: PubMed Central - PubMed

Affiliation: Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.

ABSTRACT

Background: Metabolic syndrome (MetS) is characterized by a cluster of health factors that indicate a higher risk for cardio-renal diseases. Recent evidence indicates that antioxidants from berries are alternative to attenuate oxidative stress and inflammation. We tested the hypothesis that inflammation-induced renal damage is triggered by the activation of TLR4, and subsequent modulation of redox-sensitive molecules and mitogen-activated protein kinase (MAPK) pathway.

Methods: Five-week old lean and obese Zucker rats (LZR and OZR) were fed a blueberry-enriched diet or an isocaloric control diet for 15 weeks. A glucose tolerance test and acute renal clearance experiments were performed. Gene and protein expression levels for TLR4, cytokines and phosphorylation of ERK and p38MAPK were measured. Kidney redox status and urinary albumin levels were quantified. Renal pathology was evaluated histologically.

Results: Control OZR exhibited lower glucose tolerance; exacerbated renal function parameters; increased oxidative stress. Gene and protein expression levels of TLR4 were higher and this was accompanied by increased renal pathology with extensive albuminuria and deterioration in antioxidant levels in OZR. In addition, OZR had increased phosphorylation of ERK and p38MAPK. Blueberry-fed OZR exhibited significant improvements in all these parameters compared to OZR.

Conclusion: TLR4-MAPK signaling pathway is a key to the renal structural injury and dysfunction in MetS and blueberry (BB) protect against this damage by inhibiting TLR4.

Significance: This is the first study to put forth a potential mechanism of TLR4-induced kidney damage in a model of MetS and to elucidate a downstream mechanism by which blueberry exert their reno-protective effects.

Show MeSH
Related in: MedlinePlus