title: A single dose of pirfenidone attenuates neuronal loss and reduces lipid peroxidation after kainic acid-induced excitotoxicity in the pubescent rat hippocampus.
abstract: Systemic administration of kainic acid (KA) in rodents triggers limbic seizures following selective neuronal loss in the hippocampus attributed to the excitotoxic process. Lipid peroxidation products, such as 4-hydroxynonenal, are produced by oxidative stress and are present on the hippocampus, which contribute to neuronal death in the KA excitotoxicity model. Several antioxidants are neuroprotective agents. The aim of the present study was to analyse whether pirfenidone (PFD, 5-methyl-1-phenyl-2-(1H)-pyridone), an antioxidant drug, protects the neurons in the hippocampus of pubescent rats administered with KA. We evaluated the neuroprotective effect of PFD by quantifying the surviving neurons under hematoxilin-eosin staining after using three different doses of 100, 250, and 325 mg/kg administered via an orogastric tube 90 min after KA intraperitoneal injection (12 mg/kg). Only 325 mg/kg of PFD-attenuated neuronal loss in the hippocampal areas cornu ammonis field 1 (CA1) and cornu ammonis field 3 (CA3c) was observed; therefore, this dose was used in our subsequent studies. Later, we established that PFD reduces neuronal degeneration using Fluoro-Jade B stain in the CA3c but not in the CA1, and PFD reduces the presence of 4-hydroxynonenal, a lipid peroxidation product, in the CA3 by tissue immunohistochemistry. We concluded that only a single 325 mg/kg PFD dose had a neuroprotective effect after KA brain injury. This treatment may be advantageous because adequate pharmacological therapy with PFD can be developed to protect the neuron even after an acute neuronal disorder such as seizures or hypoxic/ischemic damage.
authors.affiliation: Laboratorio de Neurobiología Celular y Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Guadalajara, Jalisco, 44421, Mexico.
authors.forename: Rubén Darío
authors.initials: RD
authors.lastname: Castro-Torres
authors.forename: Verónica
authors.initials: V
authors.lastname: Chaparro-Huerta
authors.forename: Mario Eduardo
authors.initials: ME
authors.lastname: Flores-Soto
authors.forename: Jacinto
authors.initials: J
authors.lastname: Bañuelos-Pineda
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Orozco-Suárez
authors.forename: Juan
authors.initials: J
authors.lastname: Armendáriz-Borunda
authors.forename: Carlos
authors.initials: C
authors.lastname: Beas-Zárate
mesh_terms: D000200:Action Potentials; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development; D007608:Kainic Acid / Q000633:toxicity; D015227:Lipid Peroxidation; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D011728:Pyridones; C093844:pirfenidone; D007608:Kainic Acid