Reactive
oxygen metabolites, in particular
hydroxyl radical, have been shown to be important mediators of tissue injury in several models of
acute renal failure. The aim of the present study was to examine the role of
hydroxyl radical in
glycerol-induced
acute renal failure, a model for myoglobinuric renal injury. Rats injected with
glycerol alone (8 mg/kg im following
dehydration for 24 h) developed significant
renal failure compared with dehydrated controls. Rats treated with
glycerol and a
hydroxyl radical scavenger,
dimethylthiourea (
DMTU), had significantly lower blood
urea nitrogen (BUN) and
creatinine. In contrast,
urea, which is chemically similar to
DMTU but is not a
hydroxyl radical scavenger, provided no protection. In addition,
DMTU prevented the
glycerol-induced rise in renal cortical
malondialdehyde content (a measure of lipid peroxidation that serves as a marker of
free radical-mediated tissue injury). A second
hydroxyl radical scavenger,
sodium benzoate, had a similar protective effect on renal function (as measured by both BUN and
creatinine). Because the generation of
hydroxyl radical in
biological systems requires the presence of a trace
metal such as
iron, we also examined the effect of the
iron chelator,
deferoxamine on glycerol-induced
renal failure.
Deferoxamine was also protective. The interventional agents were also associated with a marked reduction in histological evidence of renal damage. The protective effects of two
hydroxyl radical scavengers as well as an
iron chelator implicate a role for
hydroxyl radical in
glycerol-induced
acute renal failure.