Effects of L-arginine and L-NAME on ischemia-reperfusion in rat liver

Abstract

PURPOSE:To evaluated the effects of L-arginine (a NO donor) and L-NAME (N w -nitro-L-arginine methyl ester -a NOS inhibitor)on ischemia-reperfusion in rat livers. METHODS:One hundred fifty two male Wistar rats were divided into four groups: control (simulated surgery); hepatic IR; pretreatment with L-arginine plus hepatic IR; and L-NAME plus hepatic IR. The hepatocellular damage was evaluated at the first, third and seventh days after the procedures through the alanine-aminotransferase (ALT) and aspartate-aminotransaminase (AST) levels, as well as histopathological features: vascular congestion (VC); steatosis (STE); necrosis (NEC); and inflammatory infiltration (INF). The mortality rate was also evaluated. RESULTS:The pretreatment with L-NAME significantly worsened the AST levels after hepatic IR (p<0.05) at first day and L-arginine demonstrated an attenuating effect on ALT levels at seventh day (p<0.05). Furthermore, the administration of L-arginine was able to reduce the VC and STE in the seventh day after hepatic IR (p<0.05). The analysis of the mortality rates did not demonstrate any difference between the groups. Nevertheless, there was not effect of L-arginine and L-NAME on the mortality of the animals.CONCLUSION: L-arginine/NO pathway has a role in the hepatic IR because the pretreatment with L-arginine partially had attenuated the hepatocellular damage induced by hepatic IR in rats.

The role of the exogenous supply of adenosine triphosphate in the expression of Bax and Bcl2L1 genes in intestinal ischemia and reperfusion in rats

“…ATP acts by increasing nitrous oxide (NO) bioavailability, promoting vasodilation of the microvasculature and inhibition of platelet aggregation and adhesion. Operating in the interaction between endothelial surface and leukocytes, NO can mitigate inflammatory activity [18][19][20] .…”

“…NO can be cytotoxic as well as beneficial during IR. It may act both, as a protector of the lesion due to its vasodilator effect, antiplatelet and scavenger of ROS, and as a deleterious agent by interaction with superoxide radicals, forming the radical peroxynitrite 18,19 . The NO produced by endothelial cells would act to modulate IR through its vasodilator activity and counterbalance endothelin activity 18 .…”

Intravenous Arginine Administration Promotes Proangiogenic Cells Mobilization and Attenuates Lung Injury in Mice with Polymicrobial Sepsis

“…In this study, we administered intravenously 300 mg Arg/kg BW shortly after onset of CLP-induced peritonitis. A previous study showed that intraperitoneal Arg pretreatment at a dose of 200 mg/kg BW attenuated liver damage in an ischemia/reperfusion rat model [24]. In general, mice have a higher metabolic rate than that of rats.…”

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model

“…There are a variety of potential modifications of the technique detailed here and some have previously been described in the literature. Depending on the model used molecules have been delivered using inhalation 11 , epidural infusion 12 , intraperitoneal injection 17 18 21 22 , intravenous administration 10 14 15 19 23 24 or injection into the peripheral superior mesenteric vein 8 .…”

“…Points of variation include which vessels are clamped, which segment are made ischemic, whether or not the bile duct is included and the length of the period of reperfusion 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 . Additionally, when this model is used to study the impact of administration of a molecule the route of administration is also heterogeneous 8 10 11 12 14 15 17 18 19 21 22 23 24 . There are several advantages to the described approach.…”