We investigated the protective effects of Glycyrrhizae Radix extract against
peroxynitrite (ONOO-)-induced oxidative stress under in vivo as well as in vitro conditions. The extract showed strong ONOO- and
nitric oxide (NO) scavenging effects under in vitro system, in particular higher activity against ONOO-. Furthermore, elevations of plasma
3-nitrotyrosine levels, indicative of in vivo ONOO- generation and NO production, were shown using a rat in vivo ONOO(-)-generation model of
lipopolysaccharide injection plus
ischemia-reperfusion. The administration of Glycyrrhizae Radix extract at doses of 30 and 60 mg/kg
body weight/day for 30 days significantly reduced the concentrations of
3-nitrotyrosine and NO and decreased inducible
NO synthase activity. In addition, the nitrated
tyrosine protein level and
myeloperoxidase activity in the kidney were significantly lower in rats given Glycyrrhizae Radix extract than in control rats. However, the administration of Glycyrrhizae Radix extract did not result in either significant elevation of
glutathione levels or reduction of lipid peroxidation in renal mitochondria. Moreover, the in vivo ONOO- generation system resulted in renal functional impairment, reflected by increased plasma levels of
urea nitrogen and
creatinine, whereas the administration of Glycyrrhizae Radix extract reduced these levels significantly, implying that the renal dysfunction induced by ONOO- was ameliorated. The present study suggests that Glycyrrhizae Radix extract could protect the kidneys against ONOO- through scavenging ONOO- and/or its precursor NO, inhibiting
protein nitration and improving renal dysfunction caused by ONOO-.