Inhibitory effects of palm tocotrienol-rich fraction supplementation on bilirubin-metabolizing enzymes in hyperbilirubinemic adult rats

PLoS One. 2014 Feb 20;9(2):e89248. doi: 10.1371/journal.pone.0089248. eCollection 2014.


Background: Phenylhydrazine, a hemolytic agent, is widely used as a model of experimental hyperbilirubinemia. Palm tocotrienol-rich fraction (TRF) was shown to exert beneficial effects in hyperbilirubinemic rat neonates.

Aim: To investigate the effects of palm TRF supplementation on hepatic bilirubin-metabolizing enzymes and oxidative stress status in rats administered phenylhydrazine.

Methods: Twenty-four male Wistar rats were divided into two groups; one group was intraperitoneally injected with palm TRF at the dose of 30 mg/kg/day, while another group was only given vehicle (control) (vitamin E-free palm oil) for 14 days. Twenty-four hours after the last dose, each group was further subdivided into another two groups. One group was administered phenylhydrazine (100 mg/kg, intraperitoneally) and another group was administered normal saline. Twenty-four hours later, blood and liver were collected for biochemical parameter measurements.

Results: Phenylhydrazine increased plasma total bilirubin level and oxidative stress in the erythrocytes as well as in the liver, which were reduced by the pretreatment of palm TRF. Palm TRF also prevented the increases in hepatic heme oxygenase, biliverdin reductase and UDP-glucuronyltransferase activities induced by phenylhydrazine.

Conclusion: Palm tocotrienol-rich fraction was able to afford protection against phenylhydrazine-induced hyperbilirubinemia, possibly by reducing oxidative stress and inhibiting bilirubin-metabolizing enzymes in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Bilirubin / metabolism*
  • Cycas / chemistry*
  • Dietary Supplements*
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Glucuronosyltransferase / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Hyperbilirubinemia / drug therapy*
  • Hyperbilirubinemia / metabolism
  • Hyperbilirubinemia / pathology
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Phenylhydrazines / toxicity
  • Plant Oils / pharmacology*
  • Rats
  • Rats, Wistar
  • Tocotrienols / pharmacology*


  • Antioxidants
  • Phenylhydrazines
  • Plant Oils
  • Tocotrienols
  • phenylhydrazine
  • Heme Oxygenase (Decyclizing)
  • Oxidoreductases Acting on CH-CH Group Donors
  • biliverdin reductase
  • Glucuronosyltransferase
  • Bilirubin

Grant support

The study was supported by a fund from Faculty of Medicine, Universiti Kebangsaan Malaysia (FF-240-2009 grant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.