Attenuation of carbon tetrachloride-induced hepatic injury with curcumin-loaded solid lipid nanoparticles

BioDrugs. 2014 Jun;28(3):297-312. doi: 10.1007/s40259-014-0086-1.

Abstract

Background and objectives: Curcumin, an established pleiotropic agent, has potential for hepatoprotection owing to its powerful antioxidant, anti-inflammatory, and antifibrogenic properties. However, its poor bioavailability limits its use in therapeutics. In this study, we aimed to package curcumin into solid lipid nanoparticles (C-SLNs) to improve its bioavailability and compare the efficacy of C-SLNs with that of free curcumin and silymarin, a well-established hepatoprotectant in clinical use, against carbon tetrachloride (CCl4)-induced hepatic injury in rats, post-induction. A self-recovery group to which no treatment was given was also employed for quantifying self-healing of hepatic tissue, if any.

Material and methods: C-SLNs (particle size 147.6 nm), prepared using a microemulsification technique, were administered to rats post-treatment with CCl4 (1 ml/kg body weight [BW] twice weekly for 2 weeks, followed by 1.5 ml/kg BW twice weekly for the subsequent 2 weeks). The extent of liver damage and repair in terms of histopathology and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), oxidative stress markers (malondialdehyde, superoxide dismutase, and reduced glutathione) and a pro-inflammatory response marker, tumor necrosis factor (TNF)-α, were determined in both the CCl4 group and the treatment groups.

Results: C-SLNs (12.5 mg/kg) significantly (p < 0.001-0.005) attenuated histopathological changes and oxidative stress, and also decreased induction of ALT, AST, and TNF-α in comparison with free curcumin (100 mg/kg), silymarin (25 mg/kg), and self-recovery groups.

Conclusion: Curcumin could be used as a therapeutic agent for hepatic disorders, provided it is loaded into a suitable delivery system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Antioxidants / pharmacology*
  • Aspartate Aminotransferases / metabolism
  • Carbon Tetrachloride / adverse effects*
  • Curcumin / pharmacology*
  • Glutathione / metabolism
  • Lipids / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • Liver Diseases / drug therapy*
  • Male
  • Malondialdehyde / metabolism
  • Nanoparticles / administration & dosage*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Lipids
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Carbon Tetrachloride
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione
  • Curcumin