The protective effect of a nutraceuticals combination in an experimental model of liver ischemia-reperfusion

Abstract

Presenter: Carlos A Pantanali MD | Hospital das Clinicas of University of Sao Paulo Background: Ischemia-reperfusion (IR) injury is an unresolved problem in liver resection and transplantation. It has a complex pathophysiology and its injury key factors are inflammatory response, oxidative stress and apoptosis. In this context, the preoperatve nutritional state considerably affects postoperative metabolism and liver function. We aimed to evaluate the effect of a nutraceuticals combination on liver injury induced by IR in a rat model. Methods: Thirty-two male Wistar rats were used and the liver IR was performed by clamping the hepatic pedicle of the middle lobe for 60 minutes, followed by reperfusion for 4 hours. The rats were equally divided into 4 groups: group 1 – received the nutraceuticals combination by gavage for 7 days, before being subjected to liver IR; group 2 – submitted only to liver IR; group 3 – received only the nutraceuticals combination for 7 days; group 4 – normal rats (control). Blood was collected, all rats were euthanized and then samples from the injured liver were collected. Hepatocellular injury was evaluated by the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), apoptosis was analyzed using TUNEL method, TNF-alpha and caspase 3 in the liver tissue were analyzed by immunohistochemistry, lipid peroxidation was examined by the quantification of malondialdehyde (MDA) through the HPLC method and the inflammatory response was evaluated by serum interleukins 6, 10 and TNF-alpha. Results: The serum levels of AST, cytokine TNF-alpha and apoptosis were significant decreased in group 1 compared to group 2. The ALT also was reduced in group 1, but it didn’t have statistical difference with group 2. The interleukins 6 and 10, and the MDA were similar in both groups. Looking at apoptosis, the TNF-α and Caspase 3 in the liver tissue were statistically lower in group 1 compared to 2. Comparing group 2 with group 3, the nutraceuticals combination demonstrated lower levels of all studied variables. Group 2 had all variables higher than the control. Group 3 had similar levels of both transaminases, apoptosis, Caspase 3, MDA and inflammatory variables compared to normal rats, but TNF-alpha in the liver was higher this group. Conclusion: The combination of nutraceuticals given before liver IR injury is able to prevent apoptosis and inflammatory response by TNF-α, as well as limit the hepatocelullar injury. Thus, a specific nutrition can protect the hepatocytes and its mechanisms of action can be promising therapeutic targets.