Renal tubulointerstitial injury in weanling rats with hyperhomocysteinemia

Kumagai, Hiromichi; Katoh, Shigeko; Hirosawa, Keiko; Kimura, Masato; Hishida, Akira; Ikegaya, Naoki

doi:10.1111/j.1523-1755.2002.kid558.x

Cited by 68 publications

(48 citation statements)

References 31 publications

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“…However, excess intake of methionine is highly toxic to both young and adult mammals, and this toxicity far exceeds that produced by the excessive intake of any other amino acid (Harper et al 1970). Merely doubling the normal methionine intake has been shown to result in a variety of adverse outcomes including growth retardation (Benevenga et al 1976), anemia (Yokota et al 1978, vascular damage (Troen et al 2003), kidney damage and specific hypertrophy of the tubules (Kumagai et al 2002), changes in acinar pancreatic cells and iron accumulation in liver and spleen (Ekperigin and Vohra 1981). Similar changes in liver, kidney and spleen have also been observed in human patients with methioninemia (Goldfischer et al 1981).…”

Section: Introductionmentioning

confidence: 99%

Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet

Troen

French

Roberts

et al. 2006

AGE

108

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Experimentally restricting dietary calories, while maintaining adequate dietary nutrient content, extends lifespan in phylogenetically diverse species; thus suggesting the existence of conserved pathways which can modify lifespan in response to energy intake. However, in some cases the impact on longevity may depend on the quality of the energy source. In Drosophila, restriction of dietary yeast yields considerable lifespan extension whereas isocaloric restriction of dietary sugar yields only modest extension, indicating that other diet-responsive pathways can modify lifespan in this species. In rodents, restricting intake of a single amino acid -methionine -extends lifespan. Here we show that dietary methionine can modify lifespan in adult female, non-virgin Oregon-R strain Drosophila fed a chemically defined media. Compared to a diet containing 0.135% methionine and 15% glucose, high dietary methionine (0.405%) shortened maximum lifespan by 2.33% from 86 to 84 days and mean lifespan by 9.55% from 71.7 to 64.9 days. Further restriction of methionine to 0.045% did not extend maximum lifespan and shortened mean lifespan by 1.95% from 71.1 to 70.3 days. Restricting glucose from 15% to 5% while holding methionine at a concentration of 0.135%, modestly extended maximum lifespan by 5.8% from 86 to 91 days, without extending mean lifespan. All these diet-induced changes were highly significant (log-rank p<0.0001). Notably, all four diets resulted in considerably longer life spans than those typically reported for flies fed conventional yeast and sugar based diets. Such defined diets can be used to identify lifespan-modifying pathways and specific gene-nutrient interactions in Drosophila.

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Section: Introductionmentioning

confidence: 99%

Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet

Troen

French

Roberts

et al. 2006

AGE

108

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“…Kumagai et al [10]demonstrated renal interstitial injury in hyperhomocysteinemic rats; however, an effect of Cys on renal cells could not be excluded, as hyperhomocysteinemia is inevitably associated with a rise in Cys secondary to metabolism in the body. Thus, the effects of Cys and Hcy cannot be discriminated when examining cytotoxicity for renal cells in vivo.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Cytotoxicity of Cysteine and Homocysteine for Renal Epithelial Cells

Nakanishi

Akabane

Nanami

et al. 2005

Nephron Exp Nephrol

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Background: Although the cytotoxic effects of cysteine (Cys) on renal cells have been established, the effects of homocysteine (Hcy), which causes endothelial cell dysfunction, have not been well tested. We compared the direct toxicity of Hcy on renal tubular cells to that of Cys and examined the mechanism of cell toxicity. Methods: LLC-PK1 cells were incubated with test media containing 500 µM Cys or Hcy in the presence or absence of 100 µM copper. Lactate dehydrogenase release and thiobarbituric acid reactive substance were measured for estimating cytolysis and lipid peroxidation, respectively. The generation of hydrogen peroxide and hydroxyl radical, and the cell redox state were analyzed using the scopoletin method, salicylate-trap method, and glutathione (GSH) content, respectively. Superoxide dismutase, catalase, and vitamin E also were used for clarifying the mechanism of toxicity. Results: In the presence of copper (+ Cu), cytolysis at 16 h was more prominent in cells exposed to Cys than Hcy. In accordance with cytotoxicity, lipid peroxidation at 4 h of incubation, as well as hydrogen peroxide and hydroxyl radical formation in a shorter incubation, were remarkably greater in Cys + Cu than Hcy + Cu. The addition of Hcy, but not Cys, decreased GSH content significantly. Conclusion: In the presence of copper, Cys was extraordinarily more cytotoxic to renal cells than Hcy. Cytotoxicity from Hcy may be dependent upon depletion of cellular GSH, while Cys cytotoxicity is primarily dependent upon the generation of reactive oxygen species and lipid peroxidation.

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“…have shown that impaired vital organs. Diet induced chronic Hhcy also leads to alterations in cardiac and renal function [10,11] .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Homocysteine, hsCRP and Microalbuminuria in Hypertensives without and with end Organ Damage-A Case Control Study

R.S¹,

Silambanan²,

Bhaskar³

et al. 2017

jmscr

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Renal tubulointerstitial injury in weanling rats with hyperhomocysteinemia

Abstract: These results indicate that diet-induced chronic hyperhomocysteinemia could induce vascular remodeling and tubulointerstitial injury in the kidney, and that these changes were ameliorated by folate supplementation.

Cited by 68 publications

References 31 publications

Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet

Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet

Comparison of Cytotoxicity of Cysteine and Homocysteine for Renal Epithelial Cells

Evaluation of Homocysteine, hsCRP and Microalbuminuria in Hypertensives without and with end Organ Damage-A Case Control Study

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