Role of nitric oxide in lipopolysaccharide-induced oxidant stress in the rat kidney

Citation
Cj. Zhang et al., Role of nitric oxide in lipopolysaccharide-induced oxidant stress in the rat kidney, BIOCH PHARM, 59(2), 2000, pp. 203-209
Citations number
40
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
00062952 → ACNP
Volume
59
Issue
2
Year of publication
2000
Pages
203 - 209
Database
ISI
SICI code
0006-2952(20000115)59:2<203:RONOIL>2.0.ZU;2-L
Abstract
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 .