Effectiveness of vinpocetine and isosorbide-5-mononitrate on experimental schistosomiasis mansoni: Biochemical and immunohistochemical study

Acta Trop. 2018 Oct:186:16-23. doi: 10.1016/j.actatropica.2018.06.010. Epub 2018 Jun 28.

Abstract

Schistosomiasis is one of the most important tropical and subtropical devastating diseases, where praziquantel is the sole drug of choice. Praziquantel effectively kills the adult worms, however, drug resistance has been repeatedly reported. Moreover, there is currently no efficient anti-fibrotic therapy available for chronic schistosomiasis. So, novel drugs which exert anti-fibrotic efficacy are urgently needed. This research is complementary to our previous work that evaluated the anti-schistosomal effects of the anti-inflammatory vinpocetine, as well as the vasodilator and the anti-oxidant isosorbide-5-mononitrate. In the present study, we assessed the therapeutic efficacies of drugs in Swiss albino female mice experimentally infected with an Egyptian strain of Schistosoma mansoni, using some biochemical and immunohistochemical parameters. Our results revealed that both vinpocetine and isosorbide-5-mononitrate monotherapy significantly decreased hepatic nuclear factor-kappaB, 10 weeks post infection. The best effects were seen in mice administered praziquantel combined with isosorbide-5-mononitrate, as detected by reduction in hydroxyproline and collagen contents of the liver, and significant increase in the hepatic nitric oxide content. The data provides insight into the potential effects of the assessed drugs with isosorbide-5-mononitrate being more superior to vinpocetine, hence it can be used as novel adjuvant to praziquantel to alleviate schistosomal hepatic fibrosis. However, molecular mechanism/s and clinical trials are worthy to be scrutinized.

Keywords: Hydroxyproline; Nitric oxide; Nuclear factor-kappaB; Schistosoma mansoni; Vinpocetine; isosorbide-5-mononitrate.

MeSH terms

  • Animals
  • Anthelmintics / pharmacology*
  • Chemical and Drug Induced Liver Injury / pathology*
  • Disease Models, Animal
  • Drug Resistance
  • Female
  • Immunohistochemistry
  • Isosorbide Dinitrate / analogs & derivatives*
  • Isosorbide Dinitrate / pharmacology
  • Mice
  • Schistosoma mansoni / drug effects*
  • Schistosomiasis mansoni / drug therapy*
  • Vinca Alkaloids / pharmacology*

Substances

  • Anthelmintics
  • Vinca Alkaloids
  • vinpocetine
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate