A single dose of Pirfenidone attenuates neuronal cell death after excitotoxic kainic acid-induced in rat hippocampus through inhibition of microglial activation, but not TNF-ɑ and IL-1β production
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1
Biomedical Research Center of Western, Neurosciences, Mexico
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2
University of Guadalajara, Department of Molecular and Cell Biology. CUCBA, Mexico
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3
Institute for Molecular Biology in Medicine and Gene Therapy, Mexico
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4
OPD Hospital civil " Dr. Juan I. Menchaca", Mexico
Excitotoxicity plays an important role in a variety of neurological diseases such as stroke or Alzheimer’s disease. It has been known that pivotal pathways of these neuronal disorders are strongly linked to neuroinflammation. In this sense excitotoxicity KA-induced is a robust model that provides an important tool for pharmacology strategies. The pharmacological inhibition of inflammation in animal models seem to be neuroprotective. In this context, the aim of the current study was to demonstrate whether Pirfenidone (PFD, 5-methyl-1-phenyl-2-(1H)-pyridone) which has a well-known anti-inflammatory properties, protect to the hippocampal neurons from excitotoxic neuronal damage KA-induced in a juvenile 5- to 6-week old rats. We determined the neuroprotective effect of 325 mg/Kg p.g. PFD 90 min after 12 mg/Kg of KA i.p. injection in the rats. Neuronal loss and degenerated cell in CA3c hippocampal areas under Hematoxylin-Eosin and with Fluoro-Jade B stain respectively was reduced at 72 h after treatment(p<0.05). We demonstrated that the neuroprotective effect was attributed to the inhibition of microglial activation quantifying two markers by tissue immunochemistry of MHCII and Isolectine-B4 (p<0.05). There is no inhibition of mRNA TNF-ɑ and IL-1β measured by real-time PCR in hippocampal brain homogenates 6h after treatment. Further investigations needs to perform in order to elucidate the mechanics of the neuronal damage amelioration, but we infer that neuroprotection observed in our study could be attributed a partial anti-inflammatory effects of PFD. The results support that the uses of PFD in excitotoxic and neuroinflammatory diseases could be explored
Acknowledgements
We are grateful to S. Orozco-Suarez for their scientific advice, technical assistance and donate generously to us fluoro-jade B
References
1.Epstein FH, Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. New England Journal of Medicine (1994) 330(9):613-22.
2.Zheng X-Y, Zhang H-L, Luo Q, Zhu J. Kainic acid-induced neurodegenerative model: potentials and limitations. BioMed Research International (2010) 2011.
3.Salazar-Montes A, Ruiz-Corro L, López-Reyes A, Castrejón-Gómez E, Armendáriz-Borunda J. Potent antioxidant role of Pirfenidone in experimental cirrhosis. European journal of pharmacology (2008) 595(1):69-77.
Keywords:
Pirfenidone,
KA excitotoxic model,
MHCII/Isolectine-B4,
TNF-α,
IL-1beta
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Castro-Torres
RD,
Beas-Zarate
C,
Chaparro-Huerta
V,
Flores-Soto
M and
Armendáriz-Borunda
J
(2013). A single dose of Pirfenidone attenuates neuronal cell death after excitotoxic kainic acid-induced in rat hippocampus through inhibition of microglial activation, but not TNF-ɑ and IL-1β production
.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00431
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Received:
18 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Carlos Beas-Zarate, Biomedical Research Center of Western, Neurosciences, Guadalajara, Mexico, carlosbeas55@gmail.com
Dr. Juan Armendáriz-Borunda, Institute for Molecular Biology in Medicine and Gene Therapy, Guadalajara, Mexico, armdbo@gmail.com