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Pharmaceutical Research, Vol. 26, No. 4, April 2009 (# 2008) DOI: 10.1007/s11095-008-9791-0
Research Paper
Naringenin-Loaded Nanoparticles Improve the Physicochemical Properties and the Hepatoprotective Effects of Naringenin in Orally-Administered Rats with CCl4-Induced Acute Liver Failure
Feng-Lin Yen,1 Tzu-Hui Wu,1 Liang-Tzung Lin,2 Thau-Ming Cham,1,3 and Chun-Ching Lin1,3
Received September 17, 2008; accepted November 7, 2008; published online November 25, 2008
Purpose. A novel naringenin-loaded nanoparticles system (NARN) was developed to resolve the restricted bioavailability of naringenin (NAR) and to enhance its hepatoprotective effects in vivo on oral administration.
Materials and methods. Physicochemical characterizations of NARN included assessment of particle size and morphology, powder X-ray diffraction, fourier transform infrared spectroscopy, and dissolution study. In addition, to evaluate its bioactivities and its oral treatment potential against liver injuries, we compared the hepatoprotective, antioxidant, and antiapoptotic effects of NARN and NAR on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats.
Results. NARN had a significantly higher release rate than NAR and improved its solubility. NARN also exhibited more liver-protective effects compared to NAR with considerable reduction in liver function index and lipid peroxidation, in conjunction to a substantial increase in the levels of the antioxidant enzymes (P<0.05). Moreover, NARN was able to significantly inhibit the activation of caspase-3, -8, and -9 signaling, whereas NAR only markedly inhibited caspase-3 and -9 (P<0.05).
Conclusion. NARN effectively improved the release of NAR which resulted in more hepatoprotective effects mediated by its antioxidant and antiapoptotic properties. These observations also suggest that nanoformulation can improve the free drugs bioactivity on oral administration.
KEY WORDS: antiapoptotic; antioxidant; naringenin-loaded nanoparticles; oral administration; physicochemical characterization.
INTRODUCTION
Oxidative stress contributes a decisive generating factor in the pathogenesis of acute and chronic liver diseases (13). Acute liver failure (ALF) is one of the acute liver diseases that can be caused by viruses, drugs, and toxins, and can lead to the development of hepatic encephalopathy and severe impairment of liver function (4). Carbon tetrachloride (CCl4)
has been extensively used in animal models to explore chemical toxin-induced hepatic injury (57). The metabolism of CCl4 catalyzed by liver microsomal cytochrome P450 rapidly overproduces free radicals that deplete hepatic glutathione and initiate a chain lipid peroxidation of the hepatocyte membrane. This ultimately results in the overproduction of reactive oxygen species (ROS) and hepatocyte injuries (810).
The...