Effect of Rosiglitazone, the Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, on Apoptosis, Inflammatory Cytokines and Oxidative Stress in pentylenetetrazole-Induced Seizures in Kindled Mice

• Published in: Neurochemical research 2023-09, Vol.48 (9), p.2870-2880
• Main Authors: Li, Jinliang, Chen, Suping, Wang, Feilong, Zhang, Jingyu, Zeyghami, Mohammad Ali, Koohsar, Faramarz, Ayatollahi, Ali Asghar, Amini, Abolfazl
• Format: Article
• Language: English
• Subjects: Agonists; Apoptosis; Bax protein; Bcl-2 protein; Biochemistry; Biomedical and Life Sciences; Biomedicine; Caspase-3; Catalase; Cell Biology; Cytokines; Gene expression; Hippocampus; Immunomodulation; Inflammation; Interleukin 10; Interleukin 6; Kindling; Neurochemistry; Neurology; Neuroprotection; Neurosciences; Nitric-oxide synthase; Original Paper; Oxidative stress; Pentylenetetrazole; Peroxisome proliferator-activated receptors; Polymerase chain reaction; Receptors; Rosiglitazone; Seizures; Superoxide dismutase; Western blotting; γ-Interferon
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-023-03951-7

A growing body of evidence has shown that seizure can trigger inflammatory cascades through increasing the expression of several inflammatory cytokines. It has been proved that peroxisome proliferator-activated receptor-γ agonists have immunomodulatory, anti-inflammatory, and neuroprotective effects beyond the putative hypoglycemic effects. Thus, we investigated the inhibitory effect of rosiglitazone on the development of pentylenetetrazol (PTZ)-induced kindling via affecting the inflammatory pathway. Male C57BL/6 mice were randomly divided into vehicle group (0.1% DMSO), PTZ-group and rosiglitazone-PTZ-group. Kindling was induced by the administration of PTZ (40 mg/kg, i.p) every other day and mice were observed for 20 min after each PTZ injection. Twenty-four hours after the last dose, animals were euthanized and hippocampus was isolated. The level of Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase (CAT) activity were quantified in hippocampus by biochemical methods. The protein levels of IL-1β, IL‐6, IL‐10, IFN-γ, TNF‐α, caspase-3, iNOS, PPAR-γ, Bcl-2, or Bax factors were measured with western blotting. Also, the quantitative real‐time PCR were used to evaluate the mRNA expression of those factors. Pretreatment with rosiglitazone significantly prevented the progression of kindling in comparison with control group. The rosiglitazone significantly decreased the MDA level and increased the CAT, and SOD levels in the rosiglitazone treated mice compared to those in the PTZ group (P