Delayed DMSO administration protects the kidney from mercuric chloride-induced injury.
Reactive oxygen species are implicated as mediators of tissue damage in ischemic and toxic acute renal failure. Whereas many agents can inhibit renal ischemic injury, only hepatocyte growth factor, melatonin, N-acetylcysteine, and DMSO inhibit injury after mercuric chloride administration. Although it has been suggested that DMSO may chelate the mercuric ion, more recent studies suggest that it has anti-inflammatory and antioxidant effects. Acute renal failure was induced by 5 mg/kg subcutaneous injection of mercuric chloride in BALB/c mice. DMSO (3.8 ml/kg, 40% in PBS) or vehicle (PBS) was injected intraperitoneally at 0 and 24 h after mercuric chloride injection, or DMSO treatment was delayed 3 or 5 h. DMSO prevented increases in serum creatinine and tubular damage at 24 and 48 h. When DMSO treatment was delayed by 3 h, it was still beneficial; however, with a 5-h delay, the histology score and serum creatinine were not significantly decreased. DMSO partially prevented a mercuric chloride-induced decrease in glutathione peroxidase activity and completely prevented the transient decrease in superoxide dismutase activity. Neither mercuric chloride nor DMSO affected catalase activity significantly. For investigating possible effects of DMSO on cellular mercuric ion uptake, MDCK cells that were transfected with human organic anion transporter-1 were used. 203Hg uptake was inhibited 90% by N-acetylcysteine but only 5% by DMSO, indicating that the effect of DMSO is not related to chelating mercuric ion or inhibiting its uptake. It is concluded that DMSO acts in part as an antioxidant to inhibit mercuric chloride-induced acute renal injury.
Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA.
Sang-Kyung
SK
Jo
Xuzhen
X
Hu
Peter S T
PS
Yuen
Amy G
AG
Aslamkhan
John B
JB
Pritchard
James W
JW
Dear
Robert A
RA
Star
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D000818:Animals; D001707:Biopsy, Needle; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007677:Kidney Function Tests; D008297:Male; D008627:Mercuric Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D013997:Time Factors
D008627:Mercuric Chloride; D004121:Dimethyl Sulfoxide