Treatment with {alpha}-phenyl-N-tert-butylnitrone, a free radical-trapping agent, abrogates inflammatory cytokine gene expression during alloimmune activation in rat cardiac allografts

The Journal of Pharmacology and Experimental Therapeutics
Galen M PieperChristopher C Felix

Abstract

Spin-trapping nitrones such as alpha-phenyl-N-tert-butylnitrone (PBN) have traditionally been used to trap and stabilize free radicals for detection by electron paramagnetic resonance (EPR) spectroscopy. Unlike classical antioxidants, these agents have never been evaluated therapeutically in allograft transplantation. In the present study, we examined potential mechanisms of action of treatment with PBN in a rat model of acute cardiac allograft transplantation. Graft rejection was determined by histological examination and graft function determined by in situ sonomicrometry. DNA binding for nuclear factor (NF)-kappaB and activator protein (AP-1) were determined by gel shift assays. Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed for inducible nitric-oxide synthase (iNOS) and inflammatory cytokines. Histological rejection scores were elevated in untreated allografts and decreased by treatment with PBN. In situ sonomicrometry revealed decreased heart rate and distended end diastolic and end systolic segment lengths with rejection. Although PBN did not alter heart rate, it did normalize the distention of both diastolic and systolic cardiac dimension. EPR spectroscopy revealed nitros...Continue Reading

References

Jun 26, 1995·Biochemical and Biophysical Research Communications·R EdamatsuL Packer
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·H SchenkK Schulze-Osthoff
Jun 1, 1994·Chemico-biological Interactions·M MeyerP A Baeuerle
May 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C K Sen, L Packer
Nov 27, 2002·Bioscience, Biotechnology, and Biochemistry·Kieko Saito, Hisashi Yoshioka
Apr 8, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Galen M PieperMark B Adams
Jun 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ning ZhangDavid B West
Jan 13, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Galen M PieperMark B Adams

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Citations

Dec 25, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rüdiger Hardeland
Mar 24, 2005·The Journal of Pharmacology and Experimental Therapeutics·Galen M PieperCsaba Szabó

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