S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver.
BACKGROUND
Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers.


METHODS
Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70%) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase.


RESULTS
All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02).


CONCLUSIONS
This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.
Andraus
Wellington
W
Department of Gastroenterology, Universidade de São Paulo, SP, Brazil. wellington@usp.br
Souza
Gabriela Freitas Pereira de
GF
Oliveira
Marcelo Ganzarolli de
MG
Haddad
Luciana B P
LB
Coelho
Ana Maria M
AM
Galvão
Flavio Henrique
FH
Leitão
Regina Maria Cubero
RM
D'Albuquerque
Luiz Augusto Carneiro
LA
Machado
Marcel Cerqueira Cesar
MC
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D013997:Time Factors
D016166:Free Radical Scavengers; C024940:S-nitroso-N-acetylcysteine; D000111:Acetylcysteine