scholarly journals Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Chandrashekar Annamalai ◽  
Rohit Seth ◽  
Pragasam Viswanathan
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin D ◽  
Superoxide Dismutase ◽  
Iron Content ◽  
Vero Cells ◽  
Renal Cells ◽  
Dihydroxyvitamin D3 ◽  
Total Thiol ◽  
1,25 Dihydroxyvitamin D3

Globally, acute kidney injury (AKI) is associated with significant mortality and an enormous economic burden. Whereas iron is essential for metabolically active renal cells, it has the potential to cause renal cytotoxicity by promoting Fenton chemistry-based oxidative stress involving lipid peroxidation. In addition, 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, is reported to have an antioxidative role. In this study, we intended to demonstrate the impact of vitamin D on iron-mediated oxidant stress and cytotoxicity of Vero cells exposed to iohexol, a low osmolar iodine-containing contrast media in vitro. Cultured Vero cells were pretreated with 1,25-dihydroxyvitamin D3 dissolved in absolute ethanol (0.05%, 2.0 mM) at a dose of 1 mM for 6 hours. Subsequently, iohexol was added at a concentration of 100 mg iodine per mL and incubated for 3 hours. Total cellular iron content was analysed by a flame atomic absorption spectrophotometer at 372 nm. Lipid peroxidation was determined by TBARS (thiobarbituric acid reactive species) assay. Antioxidants including total thiol content were assessed by Ellman’s method, catalase by colorimetric method, and superoxide dismutase (SOD) by nitroblue tetrazolium assay. The cells were stained with DAPI (4 ′ ,6-diamidino-2-phenylindole), and the cytotoxicity was evaluated by viability assay (MTT assay). The results indicated that iohexol exposure caused a significant increase of the total iron content in Vero cells. A concomitant increase of lipid peroxidation and decrease of total thiol protein levels, catalase, and superoxide dismutase activity were observed along with decreased cell viability in comparison with the controls. Furthermore, these changes were significantly reversed when the cells were pretreated with vitamin D prior to incubation with iohexol. Our findings of this in vitro model of iohexol-induced renotoxicity lend further support to the nephrotoxic potential of iron and underpin the possible clinical utility of vitamin D for the treatment and prevention of AKI.

Rat renal 25-hydroxyvitamin D3 1- and 24-hydroxylases: their in vivo regulation

1984 ◽  
Vol 246 (2) ◽  
pp. E168-E173 ◽  
Author(s):  
Y. Tanaka ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Inorganic Phosphorus ◽  
Hydroxylase Activity ◽  
Deficient Diet ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Dietary Phosphorus ◽  
Low Calcium

The effects of thyroparathyroidectomy, parathyroid hormone, 1,25-dihydroxyvitamin D3, dietary calcium, dietary phosphorus, age, and sex on the renal 25-hydroxyvitamin D3 1- and 24-hydroxylases measured in vitro in rats have been studied. Thyroparathyroidectomy of vitamin D-deficient rats abolishes 25-hydroxyvitamin D3 1-hydroxylase activity, and administration of bovine parathyroid extract to the thyroparathyroidectomized rat restores diminished 1-hydroxylase activity. Both suppression and restoration of the enzyme activities require many hours (18-24 h) independent of rapid changes in serum calcium and inorganic phosphorus levels in response to these manipulations. Administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats suppresses 25-hydroxyvitamin D3 1-hydroxylase activity and stimulates 25-hydroxyvitamin D3 24-hydroxylase activity within 48 h. Rats maintained on a low-calcium or a low-phosphorus diet with a daily supplement of 20 IU vitamin D3 show high 25-hydroxyvitamin D3 1-hydroxylase activity and low 24-hydroxylase activity as compared with rats similarly treated but fed a diet containing adequate calcium or adequate phosphorus. When vitamin D-sufficient rats having suppressed renal 25-hydroxyvitamin D3 1-hydroxylase activity are placed on a low-calcium vitamin D-deficient diet for 7 days, the 1-hydroxylase activity is greatly stimulated in 6-wk-old rats but much less so in rats with advancing age.

Effects of 1,25-dihydroxyvitamin D3 on colonic calcium transport in vitamin D-deficient and normal rats

1984 ◽  
Vol 246 (3) ◽  
pp. G268-G273
Author(s):  
M. J. Favus ◽  
C. B. Langman
Keyword(s):  
Vitamin D ◽  
Calcium Transport ◽  
Calcium Absorption ◽  
Biological Response ◽  
Vehicle Control ◽  
Normal Diet ◽  
Dihydroxyvitamin D3 ◽  
Vitamin D Intake ◽  
1,25 Dihydroxyvitamin D3

To determine whether prior vitamin D intake influences the intestinal calcium absorptive action of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], we measured in vitro the two unidirectional transepithelial fluxes of calcium across descending colon segments from rats fed either a vitamin D-deficient or normal diet and injected with either 10, 25, or 75 ng of 1,25(OH)2D3 or vehicle alone. Vitamin D deficiency abolished net calcium absorption [J net, -2 +/- 2 vs. 12 +/- 2 (SE) nmol X cm-2 X h-1, P less than 0.001], and 10 ng of 1,25(OH)2D3 raised J net to levels found in normal rats. Larger doses (25 and 75 ng) increased J net above levels in normal rats given the same dose. In normal rats only 75 ng of 1,25(OH)2D3 increased calcium J net above vehicle control values (12 +/- 2 vs. 38 +/- 4 nmol X cm-2 X h-1, P less than 0.001). Circulating 1,25(OH)2D3 measured by radioreceptor assay was well correlated with calcium transport. For each dose of 1,25(OH)2D3 higher serum 1,25(OH)2D3 levels were reached in vitamin D-deficient rats. Only the 75-ng dose increased circulating 1,25(OH)2D3 and colonic calcium transport in normal rats. Intravenous [3H]-1,25(OH)2D3 disappeared more rapidly from the circulation of normal rats, suggesting that accelerated metabolic degradative processes for 1,25(OH)2D3 may be present in normal but not in vitamin D-deficient rats and may account for the lack of a biological response to 1,25(OH)2D3 in normal animals.

Sign in / Sign up

Export Citation Format

Share Document