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Vol. 293, Issue 3, 968-972, June 2000
Department of Pharmacology and Toxicology, University of Arkansas
for Medical Sciences, Little Rock, Arkansas
The role of inducible nitric-oxide synthase (iNOS) in
lipopolysaccharide (LPS)-induced hepatic oxidant stress was evaluated using the iNOS inhibitor L-iminoethyl-lysine
(L-NIL). Male rats were divided into three groups. One
group received LPS (Salmonella minnesota) 2 mg/kg i.v. A
second group received LPS plus L-NIL (3 mg/kg i.p.) at the
time of LPS administration followed by a second dose 3 h later. A
third group received saline i.v. At 6 h, blood and liver tissue
were collected. Serum nitrate/nitrite (metabolic products of nitric
oxide) levels were increased from 5.4 ± 1.5 nmol/ml in the
saline group to 360 ± 48 nmol/ml in the LPS group
(n = 5). Values for the LPS + L-NIL
group were significantly reduced to 35 ± 7 nmol/ml. Tissue
malondialdehyde levels were increased from 0.20 ± 0.02 nmol/mg
(n = 4) in the saline group to 0.41 ± 0.03 nmol/mg (n = 4) in the LPS group.
L-NIL significantly reduced the values in the LPS group to
0.29 ± 0.02 nmol/mg (n = 4).
4-Hydroxynonenal-protein adducts levels were increased 3.6-fold by LPS
treatment as compared with saline. L-NIL significantly reversed the levels to 1.6-fold (n = 4).
Intracellular GSH levels were decreased from 8.49 ± 0.64 nmol/mg (n = 4) in the saline group to 5.63 ± 0.51 nmol/mg in the LPS group (n = 7).
L-NIL significantly increased the levels in the LPS group
to 7.04 ± 0.46 nmol/mg (n = 7). These data
indicate that LPS-induced nitric oxide generation can result in oxidant
stress in the liver, and that inhibitors of iNOS may offer some
protection in LPS-induced hepatic toxicity.
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