Effect of Liposomal Curcumin on Acetaminophen Hepatotoxicity by Down-regulation of Oxidative Stress and Matrix Metalloproteinases

In Vivo. 2020 Mar-Apr;34(2):569-582. doi: 10.21873/invivo.11809.

Abstract

Background/aim: The hepatoprotective role of various molecules in drug-induced hepatotoxicity arouses great interest. We investigated the effect of liposomal curcumin (LCC) on experimental acetaminophen (APAP)-induced hepatotoxicity.

Materials and methods: Rats were randomly allocated into 5 groups, and the effect of two LCC concentrations was studied: group 1 - 1 ml intraperitoneal (i.p.) saline, group 2 - APAP pretreatment, group 3 - APAP+silymarin (extract of the silybum marianum with anti-inflammatory, anti-oxidant, and anti-fibrotic properties), group 4 - APAP+LCC1, group 5 - APAP+LCC2. The biomarkers of oxidative stress (nitric oxide and malondialdehyde) and antioxidant status of plasma (thiols and catalase), TNF-α, MMP-2 and MMP-9 serum levels were evaluated.

Results: An improvement in oxidative stress, antioxidant status, and TNF-α, MMP-2 and MMP-9 levels was obtained in groups pretreated with LCC compared to silymarin treatment, in a dose-dependent manner. Histopathological examination reinforced the results.

Conclusion: Liposomal curcumin improves the oxidative stress/antioxidant balance and alleviates inflammation in experimental APAP-induced hepatotoxicity.

Keywords: Curcumin; acetaminophen-induced hepatotoxicity; matrix metalloproteinases; oxidative stress; tumor necrosis factor alpha.

MeSH terms

  • Acetaminophen / adverse effects*
  • Analgesics, Non-Narcotic / adverse effects*
  • Animals
  • Antioxidants / metabolism
  • Biomarkers
  • Biopsy
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Drug Interactions
  • Immunohistochemistry
  • Liposomes*
  • Liver Function Tests
  • Male
  • Matrix Metalloproteinases / metabolism*
  • Oxidative Stress*
  • Rats
  • Tumor Necrosis Factor-alpha

Substances

  • Analgesics, Non-Narcotic
  • Antioxidants
  • Biomarkers
  • Liposomes
  • Tumor Necrosis Factor-alpha
  • Acetaminophen
  • Matrix Metalloproteinases
  • Curcumin