Fructose induces tubulointerstitial injury in the kidney of mice

Aoyama, Masahiro; Isshiki, Keiji; Kume, Shinji; Chin‐Kanasaki, Masami; Araki, Hisazumi; Araki, Shin‐ichi; Koya, Daisuke; Haneda, Masakazu; Kashiwagi, Atsunori; Maegawa, Hiroshi; Uzu, Takashi

doi:10.1016/j.bbrc.2012.02.001

Cited by 33 publications

(28 citation statements)

References 28 publications

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“…These data are consistent with recent studies that suggest that high dietary intake of fructose may also cause tubulointerstitial disease in the mouse and rat. 14, 15 …”

Section: Discussionmentioning

confidence: 99%

Fructokinase activity mediates dehydration-induced renal injury

Jimenez

Ishimoto

Lanaspa

et al. 2014

Kidney International

215

147

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The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

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“…These data are consistent with recent studies that suggest that high dietary intake of fructose may also cause tubulointerstitial disease in the mouse and rat. 14, 15 …”

Section: Discussionmentioning

confidence: 99%

Fructokinase activity mediates dehydration-induced renal injury

Jimenez

Ishimoto

Lanaspa

et al. 2014

Kidney International

215

147

View full text Add to dashboard Cite

show abstract

“…An increase in type III collagen deposition was also detected around the impaired tubular cells [69]. A similar study on mice also reported that dietary fructose could initiate the development of tubulointerstitial injury [74]. …”

Section: Fructose Causes Tubular Injury In Animal Modelsmentioning

confidence: 98%

Fructose and uric acid in diabetic nephropathy

et al. 2015

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Clinical studies have reported associations between serum uric acid levels and the development of diabetic nephropathy, but the underlying mechanisms remain elusive. There is evidence from animal studies that blocking uric acid production protects the kidney from tubulointerstitial injury, which may suggest a causal role for uric acid in the development of diabetic tubular injury. In turn, when fructose, which is endogenously produced in diabetes via the polyol pathway, is metabolised, uric acid is generated from a side-chain reaction driven by ATP depletion and purine nucleotide turnover. For this reason, uric acid derived from endogenous fructose could cause tubulointerstitial injury in diabetes. Accordingly, our research group recently demonstrated that blocking fructose metabolism in a diabetic mouse model mitigated the development of tubulointerstitial injury by lowering tubular uric acid production. In this review we discuss the relationship between uric acid and fructose as a novel mechanism for the development of diabetic tubular injury.

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“…It has been hypothesized that fructose consumption in our diet may be among the factors that contribute to the epidemic of the metabolic syndrome and, consequently, to the epidemic of chronic renal disease [1,7-11]. This hypothesis is supported by the preliminary evidence demonstrating that high fructose consumption induces kidney damages in both rats [12-14] and mice [15]. …”

Section: Introductionmentioning

confidence: 96%

Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats

Yang

Liu

Jiang³

et al. 2014

BMC Complement Altern Med

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BackgroundThe metabolic syndrome is associated with an increased risk of development and progression of chronic kidney disease. Renal inflammation is well known to play an important role in the initiation and progression of tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used spices and medicinal plants, has been demonstrated to improve diet-induced metabolic abnormalities. However, the efficacy of ginger on the metabolic syndrome-associated kidney injury remains unknown. This study aimed to investigate the impact of ginger on fructose consumption-induced adverse effects in the kidneys.MethodsThe fructose control rats were treated with 10% fructose in drinking water over 5 weeks. The fructose consumption in ginger-treated rats was adjusted to match that of fructose control group. The ethanolic extract of ginger was co-administered (once daily by oral gavage). The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-Time PCR.ResultsIn addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as characterized by focal cast formation, slough and dilation of tubular epithelial cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene expression profiles revealed that ginger suppressed fructose-stimulated monocyte chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In accord, overexpression of two important macrophage accumulation markers CD68 and F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta1 and plasminogen activator inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the downregulated ratio of urokinase-type plasminogen activator to PAI-1.ConclusionsThe present results suggest that ginger supplement diminishes fructose-induced kidney injury through suppression of renal overexpression of macrophage-associated proinflammatory cytokines in rats. Our findings provide evidence supporting the protective effect of ginger on the metabolic syndrome-associated kidney injury.

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Fructose induces tubulointerstitial injury in the kidney of mice

Cited by 33 publications

References 28 publications

Fructokinase activity mediates dehydration-induced renal injury

Fructokinase activity mediates dehydration-induced renal injury

Fructose and uric acid in diabetic nephropathy

Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats

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