Inhibition of nitric oxide modulates the effect of oral arginine supplementation in acute liver injury.
BACKGROUND
Arginine possesses numerous unique and advantageous biochemical and pharmacologic properties. We have previously shown that arginine supplementation in an acute liver injury model reduces both the extent of the liver injury and bacterial translocation. We therefore studied the role of nitric oxide on the effects of oral arginine supplementation in acute liver injury, bacterial translocation, ileal and cecal mucosal nucleotides, and RNA and DNA, to investigate pathogenetic mechanisms.


METHODS
Sprague-Dawley rats were divided into normal, liver injury control, N-nitro-L-arginine methyl ester (L-NAME), arginine, and L-NAME + arginine supplementation groups. Oral supplementation was performed daily through a nasogastric tube for 8 days. Acute liver injury was induced on the 8th day by intraperitoneal injection of D-galactosamine (1.1 g/kg body weight). Twenty-four hours after the liver injury, liver function tests, bacterial translocation, and ileal and cecal mucosal nucleotides, RNA, and DNA were evaluated.


RESULTS
Bilirubin and liver enzymes increased significantly in the L-NAME group compared with the arginine group, whereas the liver enzymes increased significantly compared with the liver injury control group. In the L-NAME group the number of bacteria translocated to the portal and arterial blood increased significantly compared with all groups. In the arginine group the bacteria translocated to the liver and mesenteric lymph nodes decreased significantly compared with the liver injury control and L-NAME groups. The ileal and cecal mucosal nucleotides, RNA, and DNA in the arginine group increased significantly compared with the normal, liver injury, and L-NAME groups.


CONCLUSIONS
Nitric oxide plays a role in the beneficial effect of the arginine supplementation in acute liver injury. It significantly improves the liver damage indicated by the increase of liver enzymes when its production was inhibited by L-NAME. Nitric oxide has a role in bacterial translocation since the number of bacteria significantly increased in arterial and portal blood when L-NAME was used to inhibit its production. Furthermore, arginine supplementation improved mucosal nucleotides, RNA, and DNA in ileum and colon.
Adawi
D
D
Dept. of Surgery, Lund University, Malmö University Hospital, Sweden.
Molin
G
G
Jeppsson
B
B
D000208:Acute Disease; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D001219:Aspartate Aminotransferases / Q000187:drug effects; D018988:Bacterial Translocation / Q000187:drug effects; D001663:Bilirubin / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D015169:Colony Count, Microbial; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005527:Food, Fortified; D005688:Galactosamine; D007413:Intestinal Mucosa / Q000187:drug effects*; D008107:Liver Diseases / Q000201:enzymology / Q000382:microbiology / Q000628:therapy*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D012313:RNA; D005688:Galactosamine; D004247:DNA; D001120:Arginine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin; D019331:NG-Nitroarginine Methyl Ester