TY - JOUR
T1 - Cytotoxicity of Senecio in macrophages is mediated via its induction of oxidative stress
AU - Bandyopadhyay, Samiran
AU - Ganguly, Sudipto
AU - Mandal, Goutam
AU - Sen, Rupashree
AU - Saha, Piu
AU - Ghosh, Monoj Kumar
AU - Sarkar, Mihir
AU - Chatterjee, Mitali
N1 - Funding Information:
The work received financial assistance from University Grants Commission, Govt. of India and Life Sciences Research Board, DRDO, Govt. of India. Dr. Samiran Bandyopadhyay was supported by an institutional project from Indian Council of Agriculture Research. Mr. Sudipto Ganguly and Mr. Goutam Mandal are recipients of Senior Research Fellowships from University Grants Commission and Council of Scientific and Industrial Research, Govt. of India, respectively. Ms. Piu Saha and Ms. Rupashree Sen are recipients of Senior Research Fellowships from Indian Council of Medical Research, Govt. of India.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Macrophages
KW - Oxidative stress
KW - Reactive nitrogen species
KW - Reactive oxygen species
KW - Senecio
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U2 - 10.1016/j.rvsc.2008.12.007
DO - 10.1016/j.rvsc.2008.12.007
M3 - Article
C2 - 19195669
AN - SCOPUS:67349106711
VL - 87
SP - 85
EP - 90
JO - Research in Veterinary Science
JF - Research in Veterinary Science
SN - 0034-5288
IS - 1
ER -