Cytotoxicity of Senecio in macrophages is mediated via its induction of oxidative stress

Samiran Bandyopadhyay, Sudipto Ganguly, Goutam Mandal, Rupashree Sen, Piu Saha, Monoj Kumar Ghosh, Mihir Sarkar, Mitali Chatterjee

Research output: Contribution to journalArticlepeer-review

Abstract

In Arunachal Pradesh and other sub-Himalayan areas of India, accidental consumption of Senecio plants by yaks is often fatal as the plant contains toxic alkaloids like Seneciophylline. The present investigation was undertaken to demonstrate the pro-oxidant effects of an ethanolic extract of Senecio chrysanthemoides (S-EtOH). S-EtOH impaired viability in macrophages, the IC50 being 13.8 ± 1.11 μg/mL. The effect of S-EtOH (1 μg/mL) on generation of reactive oxygen species (ROS) in macrophages was measured by flow cytometry using 2′,7′-dichlorofluorescein diacetate (H2DCFDA) where it caused a significant increase in the mean fluorescence channel (MFC) from 8.55 ± 0.03 to 47.32 ± 2.25 (p < 0.001). S-EtOH also effected a 3.8-fold increase in extracellular nitric oxide (NO) generation from 4.90 ± 0.72 μM to 18.79 ± 0.32 μM (p < 0.001), a 2.2-fold increase in intracellular NO production, the MFC increasing from 14.95 ± 0.48 to 33.34 ± 1.66 (p < 0.001), and concomitantly depleted non protein thiols as analyzed by flow cytometry using mercury orange, with a reduction in MFC from 632.5 ± 49.44 to 407.4 ± 12.61 (p < 0.01). Additionally, S-EtOH (14 μg/mL, 24 h) caused apoptosis as evident by increased Annexin V binding and terminal deoxynucleotidyl transferase mediated dUTP DNA nick end labeling. Taken together, the cytotoxicity of S-EtOH can be partly attributed to its capacity to inflict oxidative damage via generation of both reactive oxygen and nitrogen species culminating in apoptosis.

Original languageEnglish (US)
Pages (from-to)85-90
Number of pages6
JournalResearch in Veterinary Science
Volume87
Issue number1
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

Keywords

  • Apoptosis
  • Macrophages
  • Oxidative stress
  • Reactive nitrogen species
  • Reactive oxygen species
  • Senecio

ASJC Scopus subject areas

  • veterinary(all)

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