IMPROVED HEPATIC DAMAGE AND ENERGY METABOLISM AFTER ISCHEMIA/REPERFUSION WITH TENDER COCONUT WATER
*William B. Risinger, *Jaganathan Lakshmanan, *Baochun Zhang, *David J. Schultz, *Carolyn M. Klinge, Brian G. Harbrecht
University of Louisville, Louisville, KY
OBJECTIVE(S): Therapies for mitigating the sequelae of hepatic ischemia from transplantation, surgical resection, or shock are limited and many natural substances have medicinal value. Tender Coconut Water (TCW) from the tropical plant contains vitamins, minerals, and amino acids and is consumed for a variety of purposes. TCW also contains several biologically active substances such as phytohormones, nanoparticles, and microRNAs with diverse biologic effects. We have shown that TCW improves hepatocyte viability and decreases hepatocyte inflammation in vitro. We hypothesized that TCW would decrease hepatic damage in a rat model of hepatic ischemia/reperfusion (IR).
METHODS: Commercially available TCW was freeze-dried for storage then reconstituted in saline (1 g/ml). Rats were given 3.8 g TCW bid or saline (S) control bid for 3 days by gavage prior to being subjected to hepatic IR (60 minutes of partial hepatic ischemia followed by 6 hours of reperfusion). Rats with time-matched sham IR were controls. Samples were collected after the 6 hour reperfusion period. For proteomics, separate rats drank TCW (22 ml/day X 7 days) or water prior to sacrifice. Liver samples were lysed in SDS, reduced, digested with trypsin, and analyzed by LC-MS after labeling. Differences in proteins were assessed by Proteome Discoverer version 2.4.
RESULTS: Saline(S)- and TCW-sham IR rats had low serum ALT values at 6 hours (S-Sham, 89+28 U/L; TCW-Sham, 105+35 U/L, p=ns). Treatment with TCW bid for 3 days decreased hepatic IR-induced liver injury compared to saline controls (S-IR, 813+318 U/L; TCW-IR, 389+161 U/L, p=0.015). When analyzed for proteomic differences, consuming TCW was associated with increases in proteins involved in energy metabolism (Fatty Acid Synthase, Pyruvate Kinase, ATP-citrate Synthase), phosphorylation (Triokinase/FMN Cyclase, Serine-Threonine Protein Kinase TAO3), and cytoskeleton remodeling (FYN-binding protein 1) (all p<0.05 compared to control).
Oral TCW decreased hepatic injury in rats subjected to hepatic IR compared to untreated animals. Proteomic analysis of rats consuming TCW suggests a favorable effect for TCW on energy metabolism and cellular signaling that may contribute to the ability of the host to withstand the adverse effects of hepatic ischemia and reperfusion.
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