Antioxidants resveratrol and SkQ1 attenuate praziquantel adverse effects on the liver in Opisthorchis felineus infected hamsters

Acta Trop. 2021 Aug;220:105954. doi: 10.1016/j.actatropica.2021.105954. Epub 2021 May 9.

Abstract

Anthelmintic praziquantel (PZQ) is the drug of the choice for opisthorchiasis, schistosomiasis and other trematodiases therapy for several decades. Despite its good therapeutic performance and effective control of trematode infections, PZQ has some shortcomings; its inability to counteract disease sequelae necessitates novel therapeutic strategies. Testing of antioxidants that have proven themselves in clinical practice, in combination with this anthelmintic drug, offers new opportunities for developing alternatives to PZQ monotherapy. The effects of two antioxidants combined with PZQ on histological parameters of liver tissue were evaluated in a hamster model of opisthorchiasis felinea. Liver pathology including the parenchyma state, accumulation of neutral lipids and 4-Hydroxy-2-nonenal as a lipid peroxidation product, biochemical characteristics of hamster blood serum, and mRNA expression of inflammation- and fibrogenesis-associated genes were determined. PZQ and opisthorchiasis caused liver accumulation of lipids and glycogen. The combination of PZQ with resveratrol (RSV) or 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) significantly reduced hepatocyte changes (P = 0.009 and P = 0.009, respectively, Mann-Whitney U test) as compared with infected hamsters treated only with PZQ. RSV and SkQ1 significantly reduced cholangiocyte hyperplasia, bile duct proliferation, fibrosis, and lipid droplet and glycogen granule accumulation. The downregulation of 4-hydroxynonenal was also observed. The combinations of the anthelmintic drug with antioxidants RSV and SkQ1 ameliorate host oxidative stress and mitigate adverse effects of PZQ on hepatic parenchyma. The use of drug combinations may improve the action of standard anthelmintic agents, such as PZQ, which still remains the most effective agent against adult trematodes.

Keywords: Antioxidants; Experimental opisthorchiasis; Hepatocyte changes; Opisthorchis felineus; Praziquantel; Resveratrol; SkQ1.

MeSH terms

  • Animals
  • Anthelmintics / adverse effects*
  • Antioxidants / pharmacology*
  • Cricetinae
  • Drug Combinations
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Opisthorchis / drug effects*
  • Oxidative Stress / drug effects
  • Praziquantel / adverse effects*
  • Resveratrol / pharmacology*

Substances

  • Anthelmintics
  • Antioxidants
  • Drug Combinations
  • Praziquantel
  • Resveratrol