Assessment of nebivolol efficacy in experimental models of toxoplasmosis: insights into parasite burden reduction and neuronal protection

Parasitol Res. 2024 Aug 20;123(8):303. doi: 10.1007/s00436-024-08318-7.

Abstract

This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2 mg/kg/day and 4 mg/kg/day for 8 days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups. In the chronic model of experimental toxoplasmosis, C57/BL6 mice infected with the ME49 strain received NBV chlorhydrate 41 days post-infection and were evaluated after 10 days of treatment. NBV chlorhydrate effectively reduced cyst number and area, as well as bradyzoite burden compared to controls. Histological analysis demonstrated that NBV chlorhydrate preserved neuronal count, with the 4 mg/kg/day dose yielding counts similar to non-infected mice. Statistical analysis confirmed significant differences compared to control groups. Furthermore, immunohistochemical analysis revealed a significant reduction in iNOS labeling in the brains of mice treated with NBV chlorhydrate, indicating a decrease in nitric oxide production compared to control groups. These findings suggest NBV's potential as a promising candidate for toxoplasmosis treatment, highlighting its ability to reduce parasite burden and protect neuronal integrity. Further research is warranted to elucidate NBV's mechanisms of action and its clinical application in managing toxoplasmosis.

Keywords: Chronic Toxoplasmosis; Experimental models; In vivo; Nebivolol; Neuronal protection; Toxoplasmosis.

MeSH terms

  • Animals
  • Antiprotozoal Agents / administration & dosage
  • Antiprotozoal Agents / pharmacology
  • Antiprotozoal Agents / therapeutic use
  • Benzopyrans / pharmacology
  • Benzopyrans / therapeutic use
  • Brain* / drug effects
  • Brain* / parasitology
  • Brain* / pathology
  • Disease Models, Animal*
  • Ethanolamines / pharmacology
  • Ethanolamines / therapeutic use
  • Female
  • Mice
  • Mice, Inbred C57BL*
  • Nebivolol* / pharmacology
  • Nebivolol* / therapeutic use
  • Neurons / drug effects
  • Neurons / parasitology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Parasite Load*
  • Toxoplasma / drug effects
  • Toxoplasmosis, Animal* / drug therapy
  • Toxoplasmosis, Animal* / parasitology
  • Treatment Outcome

Substances

  • Nebivolol
  • Ethanolamines
  • Antiprotozoal Agents
  • Benzopyrans
  • Nitric Oxide
  • Nitric Oxide Synthase Type II