The pathogenesis of
multiple organ dysfunction syndrome (
MODS) in
septic shock is complicated and not fully understood. Some studies show that an overproduction of
nitric oxide (NO) leads to the refractory
hypotension and
multiple organ failure, while other studies suggest that
free radicals, e.g.
superoxide (O(2)(-)), contribute to the detrimental effect on vascular responsiveness and tissue/organ damage. Thus, this study was performed on the Wistar rat by using cecal
ligation and
puncture (CLP) to induce
septic shock-associated
MODS. We evaluated the effect of an
antioxidant melatonin in CLP-induced septic rats and demonstrated that
melatonin (3 mg/kg, i.v. at 3, 6, 12 hr after CLP) significantly (a) attenuated hyporeactivity to
norepinephrine and delayed
hypotension, (b) reduced plasma index of hepatic and renal dysfunction, (c) diminished plasma NO and
interleukin-1beta (IL-1beta) concentrations as well as aortic O(2)(-) levels, (d) reduced marked infiltration of polymorphonuclear neutrophils (PMNs) in the lung and liver tissues, and (e) promoted the survival rate at 18 hr to twofold compared with the CLP alone group. The current study underlined the inhibition of plasma NO and IL-1beta as well as aortic O(2)(-) production and the reduction of PMN infiltration may lead to the amelioration of
MODS, which may contribute to the beneficial effect of
antioxidants (e.g.
melatonin in this study) in conscious rats with
peritonitis-induced lethality. Thus, the
antioxidant could be a novel agent for the treatment of septic animals or patients in the early stage.