Lipopolysaccharide (LPS)-induced renal oxidant injury and the role of nitri
c oxide (NO) were evaluated using the inducible nitric oxide synthase (iNOS
) inhibitor L-iminoethyl-lysine (I-NIL). One group of male rats received LP
S (Salmonella minnesota; 2 mg/kg, i.v.). A second group received LPS plus L
-NIL (3 mg/kg, i.p.) A third group received saline i.v. At 6 hr, iNOS prote
in was induced in the kidney cortex, and plasma nitrate/nitrite levels were
increased from 4 +/- 2 nmol/ml in the Saline group to 431 +/- 23 nmol/mL i
n the LPS group. The value for the LPS + L-NIL group was reduced significan
tly to 42 +/- 9 nmol/ml. LPS increased blood urea nitrogen levels from 13 /- 1 to 47 +/- 3 mg/dL. LPS + L-NIL reduced these levels significantly to 2
9 +/- 2 mg/dL. Plasma creatinine levels were unchanged in all groups. Tissu
e lipid peroxidation products in the kidney were increased from 0.16 +/- 0.
01 nmol/mg in the Saline group to 0.30 +/- 0.03 nmol/mg in the LPS group. L
PS + L-NIL reduced the values significantly to 0.22 +/- 0.02 nmol/mg. Intra
cellular glutathione levels were decreased in the kidneys from 1.32 +/- 0.1
nmol/mg in the Saline group to 0.66 +/- 0.08 nmol/mg in the LPS group. LPS
+ L-NIL increased the levels significantly to 0.99 +/- 0.13 nmol/mg. LPS i
ncreased the 3-nitrotyrosine-protein adducts in renal tubules as detected b
y immunohistochemistry, indicating the generation of peroxynitrite. L-NIL d
ecreased adduct formation. These data indicated that LPS-induced NO generat
ion resulted in peroxynitrite formation and oxidant stress in the kidney an
d that inhibitors of iNOS may offer protection against LPS-induced renal to
xicity. BIOCHEM PHARMACOL 59;2:203-209, 2000. (C) 1999 Elsevier Science Inc
.