OKN-007 decreases free radical levels in a preclinical F98 rat glioma model

Patricia Coutinho De Souza, Nataliya Smith, Oluwatomisin Atolagbe, Jadith Ziegler, Charity Njoku, Megan Lerner, Marilyn Ehrenshaft, Ronald P. Mason, Bill Meek, Scott M. Plafker, Debra Saunders, Nadezda Mamedova, Rheal A. Towner

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Free radicals are associated with glioma tumors. Here, we report on the ability of an anticancer nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease free radical levels in F98 rat gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies. Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a biotin-Gd-DTPA-albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo free radicals in OKN-007-treated rat F98 gliomas. OKN-007 was found to significantly decrease (P < 0.05) free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98 tumor cells from rats administered anti-DMPO in vivo. OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2, inducible nitric oxide synthase, 3-nitrotyrosine, and malondialdehyde in ex vivo F98 glioma tissues via immunohistochemistry, as well as decrease 3-nitrotyrosine and malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that OKN-007 effectively decreases free radicals associated with glioma tumor growth. Furthermore, this method can potentially be applied toward other types of cancers for the in vivo detection of macromolecular free radicals and the assessment of antioxidants.

Original languageEnglish
Article numberFRBMD1500130
Pages (from-to)157-168
Number of pages12
JournalFree Radical Biology and Medicine
Volume87
DOIs
StatePublished - 17 Jun 2015

Fingerprint

Glioma
Oxides
Free Radicals
Rats
Tumors
Magnetic resonance
Malondialdehyde
Neoplasms
Magnetic Resonance Imaging
Spin Trapping
Imaging techniques
Antibody Specificity
Immunoelectron Microscopy
Antibodies
Signal detection
Nitric Oxide Synthase Type II
Cell membranes
Biotin
OKN 007
pyrroline

Keywords

  • (Nrf2)
  • 3-nitrotyrosine(3-NT)
  • F98 glioma
  • Freeradical
  • Glioma
  • Immuno-spin-trapping
  • In vivo
  • Inducible nitric oxide synthase (iNOS)
  • Malondialdehyde (MDA)
  • Molecular magneticresonanceimaging
  • Nuclear factor erythroid2-related factor 2
  • OKN-007

Cite this

Coutinho De Souza, P., Smith, N., Atolagbe, O., Ziegler, J., Njoku, C., Lerner, M., ... Towner, R. A. (2015). OKN-007 decreases free radical levels in a preclinical F98 rat glioma model. Free Radical Biology and Medicine, 87, 157-168. [FRBMD1500130]. https://doi.org/10.1016/j.freeradbiomed.2015.06.026
Coutinho De Souza, Patricia ; Smith, Nataliya ; Atolagbe, Oluwatomisin ; Ziegler, Jadith ; Njoku, Charity ; Lerner, Megan ; Ehrenshaft, Marilyn ; Mason, Ronald P. ; Meek, Bill ; Plafker, Scott M. ; Saunders, Debra ; Mamedova, Nadezda ; Towner, Rheal A. / OKN-007 decreases free radical levels in a preclinical F98 rat glioma model. In: Free Radical Biology and Medicine. 2015 ; Vol. 87. pp. 157-168.
@article{4c87a89393a841888912c64235104e21,
title = "OKN-007 decreases free radical levels in a preclinical F98 rat glioma model",
abstract = "Free radicals are associated with glioma tumors. Here, we report on the ability of an anticancer nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease free radical levels in F98 rat gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies. Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a biotin-Gd-DTPA-albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo free radicals in OKN-007-treated rat F98 gliomas. OKN-007 was found to significantly decrease (P < 0.05) free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98 tumor cells from rats administered anti-DMPO in vivo. OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2, inducible nitric oxide synthase, 3-nitrotyrosine, and malondialdehyde in ex vivo F98 glioma tissues via immunohistochemistry, as well as decrease 3-nitrotyrosine and malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that OKN-007 effectively decreases free radicals associated with glioma tumor growth. Furthermore, this method can potentially be applied toward other types of cancers for the in vivo detection of macromolecular free radicals and the assessment of antioxidants.",
keywords = "(Nrf2), 3-nitrotyrosine(3-NT), F98 glioma, Freeradical, Glioma, Immuno-spin-trapping, In vivo, Inducible nitric oxide synthase (iNOS), Malondialdehyde (MDA), Molecular magneticresonanceimaging, Nuclear factor erythroid2-related factor 2, OKN-007",
author = "{Coutinho De Souza}, Patricia and Nataliya Smith and Oluwatomisin Atolagbe and Jadith Ziegler and Charity Njoku and Megan Lerner and Marilyn Ehrenshaft and Mason, {Ronald P.} and Bill Meek and Plafker, {Scott M.} and Debra Saunders and Nadezda Mamedova and Towner, {Rheal A.}",
year = "2015",
month = "6",
day = "17",
doi = "10.1016/j.freeradbiomed.2015.06.026",
language = "English",
volume = "87",
pages = "157--168",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

Coutinho De Souza, P, Smith, N, Atolagbe, O, Ziegler, J, Njoku, C, Lerner, M, Ehrenshaft, M, Mason, RP, Meek, B, Plafker, SM, Saunders, D, Mamedova, N & Towner, RA 2015, 'OKN-007 decreases free radical levels in a preclinical F98 rat glioma model', Free Radical Biology and Medicine, vol. 87, FRBMD1500130, pp. 157-168. https://doi.org/10.1016/j.freeradbiomed.2015.06.026

OKN-007 decreases free radical levels in a preclinical F98 rat glioma model. / Coutinho De Souza, Patricia; Smith, Nataliya; Atolagbe, Oluwatomisin; Ziegler, Jadith; Njoku, Charity; Lerner, Megan; Ehrenshaft, Marilyn; Mason, Ronald P.; Meek, Bill; Plafker, Scott M.; Saunders, Debra; Mamedova, Nadezda; Towner, Rheal A.

In: Free Radical Biology and Medicine, Vol. 87, FRBMD1500130, 17.06.2015, p. 157-168.

Research output: Contribution to journalArticle

TY - JOUR

T1 - OKN-007 decreases free radical levels in a preclinical F98 rat glioma model

AU - Coutinho De Souza, Patricia

AU - Smith, Nataliya

AU - Atolagbe, Oluwatomisin

AU - Ziegler, Jadith

AU - Njoku, Charity

AU - Lerner, Megan

AU - Ehrenshaft, Marilyn

AU - Mason, Ronald P.

AU - Meek, Bill

AU - Plafker, Scott M.

AU - Saunders, Debra

AU - Mamedova, Nadezda

AU - Towner, Rheal A.

PY - 2015/6/17

Y1 - 2015/6/17

N2 - Free radicals are associated with glioma tumors. Here, we report on the ability of an anticancer nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease free radical levels in F98 rat gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies. Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a biotin-Gd-DTPA-albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo free radicals in OKN-007-treated rat F98 gliomas. OKN-007 was found to significantly decrease (P < 0.05) free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98 tumor cells from rats administered anti-DMPO in vivo. OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2, inducible nitric oxide synthase, 3-nitrotyrosine, and malondialdehyde in ex vivo F98 glioma tissues via immunohistochemistry, as well as decrease 3-nitrotyrosine and malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that OKN-007 effectively decreases free radicals associated with glioma tumor growth. Furthermore, this method can potentially be applied toward other types of cancers for the in vivo detection of macromolecular free radicals and the assessment of antioxidants.

AB - Free radicals are associated with glioma tumors. Here, we report on the ability of an anticancer nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease free radical levels in F98 rat gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies. Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a biotin-Gd-DTPA-albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo free radicals in OKN-007-treated rat F98 gliomas. OKN-007 was found to significantly decrease (P < 0.05) free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98 tumor cells from rats administered anti-DMPO in vivo. OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2, inducible nitric oxide synthase, 3-nitrotyrosine, and malondialdehyde in ex vivo F98 glioma tissues via immunohistochemistry, as well as decrease 3-nitrotyrosine and malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that OKN-007 effectively decreases free radicals associated with glioma tumor growth. Furthermore, this method can potentially be applied toward other types of cancers for the in vivo detection of macromolecular free radicals and the assessment of antioxidants.

KW - (Nrf2)

KW - 3-nitrotyrosine(3-NT)

KW - F98 glioma

KW - Freeradical

KW - Glioma

KW - Immuno-spin-trapping

KW - In vivo

KW - Inducible nitric oxide synthase (iNOS)

KW - Malondialdehyde (MDA)

KW - Molecular magneticresonanceimaging

KW - Nuclear factor erythroid2-related factor 2

KW - OKN-007

UR - http://www.scopus.com/inward/record.url?scp=84940049564&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2015.06.026

DO - 10.1016/j.freeradbiomed.2015.06.026

M3 - Article

C2 - 26119786

AN - SCOPUS:84940049564

VL - 87

SP - 157

EP - 168

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

M1 - FRBMD1500130

ER -

Coutinho De Souza P, Smith N, Atolagbe O, Ziegler J, Njoku C, Lerner M et al. OKN-007 decreases free radical levels in a preclinical F98 rat glioma model. Free Radical Biology and Medicine. 2015 Jun 17;87:157-168. FRBMD1500130. https://doi.org/10.1016/j.freeradbiomed.2015.06.026