Sodium thiosulfate ameliorates oxidative stress and preserves renal function in hyperoxaluric rats.
BACKGROUND
Hyperoxaluria causes crystal deposition in the kidney, which leads to oxidative stress and to injury and damage of the renal epithelium. Sodium thiosulfate (STS, Na2S2O3) is an anti-oxidant, which has been used in human medicine for decades. The effect of STS on hyperoxaluria-induced renal damage is not known.


METHODS
Hyperoxaluria and renal injury were induced in healthy male Wistar rats by chronic exposure to ethylene glycol (EG, 0.75%) in the drinking water for 4 weeks. The treatment effects of STS, NaCl or Na2SO4 were compared. Furthermore, the effects of STS on oxalate-induced oxidative stress were investigated in vitro in renal LLC-PK1 cells.


RESULTS
Chronic EG exposure led to hyperoxaluria, oxidative stress, calcium oxalate crystalluria and crystal deposition in the kidneys. Whereas all tested compounds significantly reduced crystal load, only STS-treatment maintained tissue superoxide dismutase activity and urine 8-isoprostaglandin levels in vivo and preserved renal function. In in vitro studies, STS showed the ability to scavenge oxalate-induced ROS accumulation dose dependently, reduced cell-released hydrogen peroxide and preserved superoxide dismutase activity. As a mechanism explaining this finding, STS was able to directly inactivate hydrogen peroxide in cell-free experiments.


CONCLUSIONS
STS is an antioxidant, which preserves renal function in a chronic EG rat model. Its therapeutic use in oxidative-stress induced renal-failure should be considered.
Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital and University of Bern, Inselspital, Bern, Switzerland; Department of Clinical Research, University Hospital and University of Bern, Inselspital, Bern, Switzerland.
Rakesh K
RK
Bijarnia
Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital and University of Bern, Inselspital, Bern, Switzerland; Department of Clinical Research, University Hospital and University of Bern, Inselspital, Bern, Switzerland.
Matthias
M
Bachtler
Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital and University of Bern, Inselspital, Bern, Switzerland; Department of Clinical Research, University Hospital and University of Bern, Inselspital, Bern, Switzerland.
Prakash G
PG
Chandak
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Harry
H
van Goor
Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital and University of Bern, Inselspital, Bern, Switzerland; Department of Clinical Research, University Hospital and University of Bern, Inselspital, Bern, Switzerland.
Andreas
A
Pasch
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004195:Disease Models, Animal; D006959:Hyperoxaluria / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013885:Thiosulfates / Q000494:pharmacology*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013885:Thiosulfates; C017717:sodium thiosulfate