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Ironjustic
Sat, Apr-30-05, 17:18
Nephrol Dial Transplant. 2005 Apr 26; [Epub ahead of print]
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Beneficial effect of vitamin E supplementation on the
biochemical and kinetic properties of Tamm-Horsfall
glycoprotein in hypertensive and hyperoxaluric patients.

Sumitra K, Pragasam V, Sakthivel R, Kalaiselvi P,
Varalakshmi P.

Department of Medical Biochemistry, Dr ALM Post Graduate
Institute of Basic Medical Sciences, University of Madras,
Taramani Campus, Taramani, Chennai, Tamilnadu, India.

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 = 200) and stone formers (n = 200)
were each subdivided into two groups. One group (n =
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 = 100) did not receive vitamin E (placebo
controls). Age and sex-matched controls (n = 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 E-treated
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 to renal tissues that remained
unchecked by standard drug therapies. The normalization
of the kinetic properties of THP following vitamin E
supplementation is in support of our hypothesis.

PMID: 15855216 [PubMed - as supplied by publisher]

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