TY - JOUR T1 - Oxidant Stress in Rat Liver after Lipopolysaccharide Administration: Effect of Inducible Nitric-Oxide Synthase Inhibition JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 968 LP - 972 VL - 293 IS - 3 AU - Chaojie Zhang AU - Lisa M. Walker AU - Jack A. Hinson AU - Philip R. Mayeux Y1 - 2000/06/01 UR - http://jpet.aspetjournals.org/content/293/3/968.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -