2,3-Dihydroxybenzoic acid. Effect on mortality rate in a septic rat model
R. A. Pearce, R. J. Finley, R. A. Mustard Jr and J. H. Duff
Neutrophil-derived oxygen-free radicals may play a role in organ
dysfunction associated with generalized sepsis. A rat model was used to
test the effects of two free radical scavengers, dimethyl sulfoxide (DMSO)
and 2,3-dihydroxybenzoic acid (2,3-DHB), on mortality from intra-abdominal
sepsis produced by cecal ligation and perforation. Being an iron-chelating
agent, 2,3-DHB may have an additional bacteriostatic effect. Therapeutic
regimens included no treatment; gentamicin sulfate (2 mg given
intraperitoneally [IP] every eight hours); DMSO (2 g/24 hr given IP every
eight hours in divided doses); 2,3-DHB (35 mg/kg given IP every eight
hours); and combinations of gentamicin with each free radical scavenger. No
statistically significant improvement in survival was obtained by
therapeutic intervention with gentamicin alone, DMSO alone, 2,3-DHB alone,
or gentamicin in combination with DMSO. When used in combination with
gentamicin, 2,3-DHB yielded a statistically significant improvement in
survival when compared with gentamicin alone or with no treatment. These
results show that 2,3-DHB when used in combination with gentamicin has a
beneficial effect on mortality following intra-abdominal sepsis in this
model.
