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Fluvastatin and atorvastatin induce programmed cell death in the brain eating amoeba Naegleria fowleri

Aitor Rizo-Liendo1, Ines Sifaoui2, Iñigo Arberas-Jiménez1

  • 1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, 38203 Islas Canarias, Spain; Departamento de Obstetricia, Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad De La Laguna, La Laguna, Tenerife, 38203 Islas Canarias, Spain.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|August 4, 2020
PubMed

Insights

Flাইভastatin and atorvastatin show promise for treating Primary Amoebic Encephalitis (PAM). These statins effectively kill Naegleria fowleri by inducing programmed cell death with low toxicity, offering a potential new therapy.

Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Pharmacology

Background:

  • Naegleria fowleri causes Primary Amoebic Encephalitis (PAM), a nearly always fatal infection.
  • Current PAM treatments have severe side effects and limited efficacy.
  • Statins have demonstrated in vitro activity against Naegleria fowleri with low toxicity.

Purpose of the Study:

  • To investigate the cell death pathways induced by fluvastatin and atorvastatin in Naegleria fowleri.
  • To compare the efficacy and cell death mechanisms of fluvastatin and atorvastatin against miltefosine and amphotericin B.
  • To determine if statins induce programmed cell death (PCD) to avoid inflammation.

Main Methods:

  • Treatment of Naegleria fowleri trophozoites with fluvastatin and atorvastatin.
  • Assessment of cell death markers including chromatin condensation, membrane integrity, mitochondrial potential, ATP levels, and ROS generation.
  • Comparison of statin-induced cell death with that induced by miltefosine and amphotericin B.

Main Results:

  • Both fluvastatin and atorvastatin induced programmed cell death (PCD) in Naegleria fowleri.
  • Observed PCD indicators included chromatin condensation, cell membrane damage, mitochondrial dysfunction, and ATP depletion.
  • Statins also triggered reactive oxygen species (ROS) generation in the treated amoebae.

Conclusions:

  • Fluvastatin and atorvastatin are potential candidates for PAM therapy due to their efficacy at low concentrations and low toxicity.
  • Statins induce PCD in Naegleria fowleri, which may prevent inflammatory responses associated with necrosis.
  • Developing statin-based therapies could offer a safer and more effective treatment for PAM.
Keywords:
AtorvastatinFluvastatinNaegleriaPCDStatinsTherapy

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