The flip side of reactive oxygen species in the tropical disease-Amoebiasis

Chem Biol Drug Des. 2021 Nov;98(5):930-942. doi: 10.1111/cbdd.13950. Epub 2021 Sep 18.

Abstract

Entamoeba histolytica is the conductive agent of amoebiasis. Upon the parasite's infection, macrophages and neutrophils are activated by interferon γ, IL-13 and tumour necrosis factor. These immune cells then carry out the amoebicidal activity by releasing nitric oxide synthase and reactive oxygen species (ROS). This review talks about the protective and destructive role of ROS in Eh. E. histolytica has defence strategies against oxidative stress which is a result of excess ROS production. They possess antioxidants for their defence such as L-Cysteine, flavodiiron proteins, peroxiredoxin and trichostatin A, which contribute to the parasite's virulence. The ROS are harmful to the host cells as excess ROS production stimulates cell death by mechanisms like apoptosis and necroptosis. NADPH oxidase (NOX) is a key source of ROS in mammalian cells and causes apoptosis of host cells via the protein kinase transduction pathway. This review provides insights into why NOX inhibitors that could be a potent antiparasitic drug, is not effective for in vivo purposes. This paper also gives an insight into a solution that could be a potent source in generating new treatment and vaccines for amoebiasis by targeting parasite development.

Keywords: E. histolytica; L-cysteine; NOX; ROS; apoptosis; biosynthetic pathways; cysteine proteases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amebiasis / drug therapy*
  • Apoptosis
  • Entamoeba histolytica / drug effects*
  • Enzyme Inhibitors / chemistry
  • Humans
  • Interferons / metabolism
  • Interleukin-13 / metabolism
  • Macrophages
  • NADPH Oxidases / antagonists & inhibitors
  • Neutrophils / metabolism
  • Oxidative Stress
  • Reactive Oxygen Species / chemistry*
  • Reactive Oxygen Species / pharmacology
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Enzyme Inhibitors
  • Interleukin-13
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Interferons
  • NADPH Oxidases

Associated data

  • RefSeq/Q01957
  • RefSeq/Q01958
  • RefSeq/P36184
  • RefSeq/Q27643
  • RefSeq/Q95030
  • RefSeq/Q27645
  • RefSeq/Q9BI10
  • RefSeq/Q8I8E0
  • RefSeq/Q8I8D9
  • RefSeq/Q8I8D8
  • RefSeq/B1N5A5
  • RefSeq/Q8I8D6
  • RefSeq/Q8I8D5
  • RefSeq/Q8I8D4
  • RefSeq/Q8I8D3
  • RefSeq/Q8I8D2
  • RefSeq/Q8I8D1
  • RefSeq/Q8I8D0
  • RefSeq/Q8I8C9
  • RefSeq/Q9U7F7