Reduction of oxidative stress and liver injury following silymarin and praziquantel treatment in mice with Mesocestoides vogae (Cestoda) infection.
Oxidative stress is a common mechanism contributing to hepatic damage and fibrogenesis in a variety of liver disorders. The liver is the target organ for many parasitic infections, hence there is a great demand for the development of novel treatment strategies. In the present study conducted on mice infected with larval stage of Mesocestoides vogae, we investigated effects of therapy with praziquantel (PZQ) alone and in combination with silymarin on liver GSH content, lipid peroxidation and larval reduction. Proliferation of liver cells by means of BrdU incorporation into DNA and production of superoxide anions by peritoneal adherent cells was measured to assess the antioxidant activity of silymarin. Drug administration was carried on from day 15 post infection (p.i.) for ten consecutive days and examination was performed during 20 days of follow-up the therapy. Larval M. vogae infection caused liver damage and triggered extensive oxidative stress, resulting in the abolishment of GSH redox balance and ROS-induced lipid peroxidation. PZQ administration caused short-term decline of GSH levels in healthy mice. Low GSH levels in infected mice were elevated gradually in response to the drug, but respiratory burst in cells was not reduced. Silymarin in combination with PZQ showed strong direct antioxidant capacity and stimulated the larvicidal effect of praziquantel. Treatment with PZQ and silymarin downregulated the generation of superoxide anions, prevented lipid peroxidation, stimulated GSH synthesis and proliferation of hepatocytes in infected livers. These findings demonstrated that silymarin can markedly decrease the liver injury and its co-administration with PZQ potentiate effect of therapy, probably due to the down-regulation of fibrogenesis.
Velebný
Samuel
S
Parasitological Institute, Slovak Academy of Sciences, Hlinkova 3, 040 01 Košice, Slovak Republic.
Hrčkova
Gabriela
G
Königová
Alžbeta
A
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002590:Cestode Infections / Q000188:drug therapy / Q000469:parasitology; D004359:Drug Therapy, Combination; D015227:Lipid Peroxidation; D008099:Liver / Q000166:cytology / Q000293:injuries / Q000469:parasitology / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008645:Mesocestoides / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D011223:Praziquantel / Q000494:pharmacology / Q000627:therapeutic use*; D012838:Silymarin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000871:Anthelmintics; D000975:Antioxidants; D012838:Silymarin; D011223:Praziquantel