Aminoguanidine, an inducible nitric oxide synthase inhibitor, plus                 N-acetylcysteine treatment reduce the lipopolysaccharideaugmented hepatotoxicity in                 rats with cirrhosis

Hepatic cirrhosis is produced in rats by administration of thioacetamide (TAA) (0.3 g/L tap water for a period of three months). This treatment caused an increase in oxidative stress in the liver. Lipopolysaccharide (LPS) administration (5 mg/kg) to rats with cirrhosis was observed to increase hepatotoxicity as well as oxidative stress according to biochemical and histopathological findings. However, aminoguanidine (AG), an inducible nitric oxide synthase (iNOS) inhibitor, plus N-acetylcysteine (NAC) treatment reduced the LPS-augmented hepatotoxicity in rats with cirrhosis without making any changes in oxidative stress in the liver.

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Effects of Early Neuronal and Delayed Inducible Nitric Oxide Synthase Blockade on Cardiovascular, Renal, and Hepatic Function in Ovine Sepsis

Anesthesiology ◽

10.1097/aln.0b013e3181fc5588 ◽

2010 ◽

Vol 113 (6) ◽

pp. 1376-1384 ◽

Cited By ~ 14

Author(s):

Matthias Lange ◽

Atsumori Hamahata ◽

Daniel L. Traber ◽

Yoshimitsu Nakano ◽

Aimalohi Esechie ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Nitric Oxide Synthase Inhibitor ◽

Nitrite Nitrate ◽

Synthase Inhibitor ◽

Plasma Nitrite ◽

Oxide Synthase ◽

Organ Dysfunctions ◽

Inducible Nitric Oxide

Background Recent evidence suggests that nitric oxide produced via the neuronal nitric oxide synthase is involved mainly in the early response to sepsis, whereas nitric oxide derived from the inducible nitric oxide synthase is responsible during the later phase. We hypothesized that early neuronal and delayed inducible nitric oxide synthase blockade attenuates multiple organ dysfunctions during sepsis. Methods Sheep were randomly allocated to sham-injured, nontreated animals (n = 6); injured (48 breaths of cotton smoke and instillation of Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n = 6). Results The injury induced arterial hypotension, vascular leakage, myocardial depression, and signs of renal and hepatic dysfunctions. The treatment significantly attenuated, but did not fully prevent, the decreases in mean arterial pressure and left ventricular stroke work index. Although the elevation of creatinine levels was partially prevented, the decreases in urine output and creatinine clearance were not affected. The injury-related increases in bilirubin levels, international normalized ratio, and lipid peroxidation in liver tissue were significantly attenuated. Although plasma nitrite/nitrate levels were significantly increased versus baseline from 12-24 h in controls, plasma nitrite/nitrate levels were not increased in treated animals. Conclusions The combination treatment shows potential benefit on sepsis-related arterial hypotension and surrogate parameters of organ dysfunctions in sheep. It may be crucial to identify the time course of expression and activation of different nitric oxide synthase isoforms in future investigations.

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