Role of hepatic nitric oxide synthases in rats with thioacetamide-induced acute liver failure and encephalopathy.
BACKGROUND
Hepatic encephalopathy is neuropsychiatric derangement secondary to hepatic decompensation or portal-systemic shunting. Nitric oxide (NO) synthase inhibition aggravates encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure, suggesting a protective role of NO. This study investigated the roles of endothelium-derived constitutive NO synthase (eNOS) and inducible NOS (iNOS) in the liver of rats with fulminant hepatic failure and encephalopathy.


METHODS
Male Sprague-Dawley rats (300-350 g) were randomized to receive TAA 350 mg/kg/day, by intraperitoneal injection or normal saline for 3 days. Severity of encephalopathy was assessed with the Opto-Varimex animal activity meter. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin were measured. Hepatic iNOS and eNOS RNA and protein expressions were assessed by reverse transcription-polymerase chain reaction and Western blot analyses, respectively.


RESULTS
The TAA group showed lower motor activity counts than the normal saline group. Hepatic eNOS, but not iNOS, mRNA and protein expressions were enhanced in the TAA group. In addition, hepatic eNOS mRNA expression was negatively correlated with total movement but positively correlated with ALT and AST. Protein expression of hepatic eNOS was positively correlated with ALT, AST and bilirubin.


CONCLUSIONS
Upregulation of hepatic eNOS was observed in rats with TAA-induced fulminant hepatic failure and encephalopathy, which might play a regulatory role.
Huang
Hui-Chun
HC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
Wang
Sun-Sang
SS
Chan
Cho-Yu
CY
Chen
Yi-Chou
YC
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Chu
Chi-Jen
CJ
Lin
Han-Chieh
HC
Lu
Rei-Hwa
RH
Lee
Shou-Dong
SD
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015153:Blotting, Western; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity*
D013853:Thioacetamide; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin