Studies on Calcium Oxalate Binding Proteins: Effect of Lipid Peroxidation

Selvam, Ramasamy; Kalaiselvi, Periandavan

doi:10.1159/000045978

Cited by 15 publications

(10 citation statements)

References 18 publications

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“…In our laboratory, we documented an in vitro oxidative modification of a 45 kDa protein that we had isolated [24]. This finding suggests that loss of -SH groups has a profound effect on inhibitory properties in a crystallizing medium [25]. This indicates that vitamin E mediates its action on protein kinetic behaviour primarily by curbing oxidative damage to the protein of the human subjects in vivo.…”

Section: Beneficial Effect Of Vitamin E Supplementation 1413mentioning

confidence: 99%

Beneficial effect of vitamin E supplementation on the biochemical and kinetic properties of Tamm–Horsfall glycoprotein in hypertensive and hyperoxaluric patients

Sumitra

Viswanathan

Sakthivel

et al. 2005

Nephrology Dialysis Transplantation

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Background. This study aimed to assess the therapeutic efficacy of oral vitamin E supplementation on the biochemical and kinetic properties of Tamm-Horsfall glycoprotein (THP) in hypertensive and hyperoxaluric patients. Methods. Newly detected hypertensives (n ¼ 200) and stone formers (n ¼ 200) were each subdivided into two groups. One group (n ¼ 100) was administered the antioxidant vitamin E at 400 mg/day given as an oral supplement along with standard therapeutic drugs for hypertension and hyperoxaluria and the patients were followed for a period of 9 months. The other group (n ¼ 100) did not receive vitamin E (placebo controls). Age and sex-matched controls (n ¼ 100) were monitored simultaneously. THP was isolated from 24 h urine samples before and at the end of every third month during a period of 9 months from the vitamin Etreated hypertensive and hyperoxaluric groups. THP samples were also collected from control subjects, and at the end of the ninth month from placebo controls. The isolated protein was assessed for purity by SDS-PAGE. The purity-checked proteins were subjected to spectrophotometric crystallization assay, calcium oxalate (CaOx) crystal interaction studies, and biochemical analysis of sialic acid, thiol and carbonyl content. Plasma superoxide, hydroxyl radical, hydrogen peroxide and vitamin E levels as well as superoxide dismutase and catalase activities were also monitored. Results. The THP from the hypertensive and hyperoxaluric subjects exhibited a significant promoting effect on the nucleation and aggregation phases and caused a concomitant increase in CaOx crystal interaction. The altered kinetic properties of THP in these subjects were strongly associated with increased carbonyl content and with decreased thiol and sialic acid contents. Oral administration of vitamin E to these patients caused near normalization of these biochemical alterations and satisfactorily restored the kinetic properties of THP to near normal activity. At the end of 9 months, THP isolated from placebo controls (hypertensive and hyperoxaluric) showed highly aggregated calcium oxalate monohydrate crystals as observed by light microscopy. In contrast, vitamin E-supplemented patients showed CaOx dihydrate crystals that were similar to control THP. There was an imbalance in the oxidant and antioxidant levels. For the oxidants, superoxide, hydrogen peroxide and hydroxyl radical levels were increased, and for the antioxidants, there was loss of antioxidant enzyme activities and a decline in plasma vitamin E level in both hypertensive and hyperoxaluric patients. Supplementary antioxidant (vitamin E) corrected this imbalance to near normal conditions. Conclusion. We hypothesize that the loss of THP inhibitory activity in the hypertensive and hyperoxaluric patients in a crystallizing medium is mediated primarily by oxidative damage to this protein. The possible occurrence of renal stones in essential hypertensive subjects, and the risk of recurrence in hyperoxaluric subjects, may be explained by oxidative damage ...

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Section: Beneficial Effect Of Vitamin E Supplementation 1413mentioning

confidence: 99%

Beneficial effect of vitamin E supplementation on the biochemical and kinetic properties of Tamm–Horsfall glycoprotein in hypertensive and hyperoxaluric patients

Sumitra

Viswanathan

Sakthivel

et al. 2005

Nephrology Dialysis Transplantation

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“…Azelaic acid would have two important anti-atherogenic properties: one, as other dicarboxylic acids, it would have great affinity for calcium and precipitate calcium in lipid-rich domains [219][220][221][222]. This might account for the unusually high calcification associated with lipid core domains.…”

Section: Azelaic Acid a Lipid Peroxidation-derived Lipophilic Dicarbmentioning

confidence: 99%

Lipid peroxidation and decomposition — Conflicting roles in plaque vulnerability and stability

Parthasarathy

Litvinov

Selvarajan

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The low density lipoprotein (LDL) oxidation hypothesis has generated considerable interest in oxidative stress and how it might affect atherosclerosis. However, the failure of antioxidants, particularly vitamin E, to affect the progression of the disease in humans has convinced even staunch supporters of the hypothesis to take a step backwards and reconsider alternatives.Preponderant evidence for the hypothesis came from animal antioxidant intervention studies. In this review we point out basic differences between animal and human atherosclerosis development and suggest that human disease starts where animal studies end. While initial oxidative steps in the generation of early fatty streak lesions might be common, the differences might be in the steps involved in the decomposition of peroxidized lipids into aldehydes and their further oxidation into carboxylic acids. We suggest that these steps may not be amenable to attenuation by antioxidants and antioxidants might actually counter the stabilization of plaque by preventing the formation of carboxylic acids which are anti-inflammatory in nature. The formation of such dicarboxylic acids may also be conducive to plaque stabilization by trapping calcium.We suggest that agents that would prevent the decomposition of lipid peroxides and promote the formation and removal of lipid hydroxides, such as paraoxonase (PON 1) or apo A1/high density lipoprotein (HDL) might be more conducive to plaque regression. KeywordsAtherosclerosis; aldehydes; dicarboxylation; inflammation; calcification Oxidation hypothesis of atherosclerosisAtherosclerosis is the major manifestation of cardiovascular diseases. The role of lipoproteins in atherosclerosis development has been a topic of interest for over five decades. It is now established beyond doubt that high levels of low density lipoprotein (LDL) and low levels of high density lipoprotein (HDL) contribute significantly to the development and progression of cardiovascular diseases [1][2][3][4][5].The biochemical processes that contributed to the formation of early atherosclerotic lesions, the fatty streak lesions, are still under debate. The LDL oxidation hypothesis was put forward in the eighties to explain the formation of fatty streak lesions and over 4000 publications and countless reviews have appeared on the topic to date [6][7][8][9][10][11] providing evidence for the presence *Address correspondence to: Sampath Parthasarathy, Ph.D., M.B.A*. N-850 Doan Hall, 410 W. 10 th Avenue, Ohio State University, Columbus, OH 43210, Tel: (614) Fax: (614) 292-9259, E-mail: spartha@osumc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all ...

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“…For most human diseases, increased formation of reactive oxygen species is secondary to primary disease process (2). Similarly association of urolithiasis and free radicals has been reported (3). Experiments performed on animals (3,4), cultures (5) and human sera (6) have revealed that there is presence of enhanced oxidative stress in stone forming conditions.…”

Section: Introductionmentioning

confidence: 83%

“…Experiments performed on animals (3,4), cultures (5) and human sera (6) have revealed that there is presence of enhanced oxidative stress in stone forming conditions. Oxalate is known to induce lipid peroxidation by unknown mechanism which causes disruption of the structural integrity of the membranes (3,7). Superoxide dismutase (SOD) is an inbuilt defense mechanism to fight back peroxidative stress.…”

Section: Introductionmentioning

confidence: 99%