Effect of fenofibrate on plasma level of BDNF and brain oxidative stress markers in pentylenetetrazole-induced kindling seizure in mice

authors:

avatar Nahid Sarahian , avatar Mohammad Taghi Mohammadi , * , avatar Shima Shahyad ORCID , avatar Mohsen Rezaei

Koomesh: Vol.23, issue 5; 636-645
published online: December 02, 2021
article type: Research Article
received: January 01, 2021
accepted: April 02, 2021

how to cite: Sarahian N, Mohammadi M T, Shahyad S, Rezaei M. Effect of fenofibrate on plasma level of BDNF and brain oxidative stress markers in pentylenetetrazole-induced kindling seizure in mice. koomesh. 2021;23(5):e153296. 

Abstract

Introduction: The neuroprotective effect and pleiotropic functions of PPARα agonists (peroxisome proliferator activated receptor-alpha) such as fenofibrate and bezafibrate have been demonstrated by the previous studies. The current study evaluated the antiepileptic effects and neuroprotective functions of fenofibrate in pentylenetetrazole (PTZ)-induced kindling seizure in mice. Materials and Methods: Adult male NMRI mice were randomly assigned into three groups (n=8): Control, untreated kindled mice and fenofibrate-treated kindled animals. Repeated intraperitoneal injections of PTZ (45 mg/kg) once every 48 hours were used to develop the kindling seizure for 21 days. Treated mice were administered orally fenofibrate at doses of 30 mg/kg/day. Plasma level of brain-derived neurotrophic factor (BDNF), brain level of malondialdehyde (MDA) and histopathological changes were evaluated at termination of the study. Results: Fenofibrate administration considerably improved the seizure latency in treated kindled mice. Fenofibrate significantly (P

References

  • 1.

    Sazhina T, Sitovskaya D, Zabrodskaya YM, Bazhanova E. Functional imbalance of glutamate-and GABAergic neuronal systems in the pathogenesis of focal drug-resistant epilepsy in humans. Bull Exp Biol Med 2020; 168: 529-532.

  • 2.

    Schousboe A, Wellendorph P, Frlund B, Clausen RP, Krogsgaard-Larsen P. Astrocytic GABA transporters: pharmacological properties and targets for antiepileptic drugs. Glial Amino Acid Transporters 2017; 16: 283-296.

  • 3.

    Puttachary S, Sharma S. Seizure-induced oxidative stress in temporal lobe epilepsy. Biomed Res Int 2015; 2015: 745613.

  • 4.

    El-Missiry MA, Othman AI, Amer MA, Sedki M, Ali SM, El-Sherbiny IM. Nanoformulated ellagic acid ameliorates pentylenetetrazol-induced experimental epileptic seizures by modulating oxidative stress, inflammatory cytokines and apoptosis in the brains of male mice. Metab Brain Dis 2020; 35: 385-399.

  • 5.

    Ravizza T, Vezzani A. Pharmacological targeting of brain inflammation in epilepsy: Therapeutic perspectives from experimental and clinical studies. Epilepsia Open 2018; 3: 133-142.

  • 6.

    Xu YL, Li XX, Zhuang SJ, Guo SF, Xiang JP, Wang L, et al. Significant association of BDNF rs6265 G> A polymorphism with susceptibility to epilepsy: a meta-analysis. Neuropsychiatr Dis Treat 2018; 14: 1035.

  • 7.

    Conner JM, Lauterborn JC, Yan Q, Gall CM, Varon S. Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport. J Neurosci 1997; 17: 2295-2313.

  • 8.

    Anderson KD, Alderson RF, Altar CA, DiStefano PS, Corcoran TL, Lindsay RM, et al. Differential distribution of exogenous BDNF, NGF, and NT3 in the brain corresponds to the relative abundance and distribution of highaffinity and lowaffinity neurotrophin receptors. J Comp Neurol 1995; 357: 296-317.

  • 9.

    Martnez-Levy G, Rocha L, Lubin F, Alonso-Vanegas M, Nani A, Buentello-Garca R, et al. Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy. Neuroscience 2016; 314: 12-21.

  • 10.

    Alvim M, Yasuda C, Morita M, Coan A, Barbosa R, Vieira E, et al. The relationship between blood serum BDNF and seizure frequency in temporal lobe epilepsy patients. J Neurol Sci 2017; 381: 334.

  • 11.

    Patel V, Katyal J, Rashid H, Gupta YK. Effect of pentylenetetrazole-induced seizures on serum brain-derived neurotrophic factor (BDNF) levels and cognition in rats. Int J Epilepsy 2018; 5: A0047.

  • 12.

    Luo Y, He Q, Kuang G, Jiang Q, Yang J. PPAR-alpha and PPAR-beta expression changes in the hippocampus of rats undergoing global cerebral ischemia/reperfusion due to PPAR-gamma status. Behav Brain Funct 2014; 10: 21.

  • 13.

    Gautier S, Ouk T, Ptrault M, Ptrault O, Brzowski V, Bordet R. PPAR-Alpha agonist used at the acute phase of experimental ischemic stroke reduces occurrence of thrombolysis-induced hemorrhage in rats. PPAR Res 2015; 2015: 1-6.

  • 14.

    Guo Q, Wang G, Namura S. Fenofibrate improves cerebral blood flow after middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 2010; 30: 70-78.##https://doi.org/10.1038/jcbfm.2009.201.

  • 15.

    Villapol S. Roles of peroxisome proliferator-activated receptor gamma on brain and peripheral inflammation. Cell Mol Neurobiol 2018; 38: 121-132.

  • 16.

    Gel P, Vingtdeux V, Potey C, Drobecq H, Ghestem A, Melnyk P, et al. Recovery of brain biomarkers following peroxisome proliferator-activated receptor agonist neuroprotective treatment before ischemic stroke. Proteome Sci 2014; 12: 24.

  • 17.

    Chistyakov DV, Aleshin SE, Astakhova AA, Sergeeva MG, Reiser G. Regulation of peroxisome proliferator-activated receptors (PPAR) alpha and -gamma of rat brain astrocytes in the course of activation by toll-like receptor agonists. J Neurochem 2015; 134: 113-124.

  • 18.

    Wang G, Liu X, Guo Q, Namura S. Chronic treatment with fibrates elevates superoxide dismutase in adult mouse brain microvessels. Brain Res 2010; 1359: 247-255.

  • 19.

    Bhateja DK, Dhull DK, Gill A, Sidhu A, Sharma S, Reddy BK, et al. Peroxisome proliferator-activated receptor- activation attenuates 3-nitropropionic acid induced behavioral and biochemical alterations in rats: possible neuroprotective mechanisms. Eur J Pharmacol 2012; 674: 33-43.

  • 20.

    Chang KL, Pee HN, Tan WP, Dawe GS, Holmes E, Nicholson JK, et al. Metabolic profiling of CHO-AbetaPP695 cells revealed mitochondrial dysfunction prior to amyloid-beta pathology and potential therapeutic effects of both PPARgamma and PPARalpha Agonisms for Alzheimer's disease. J Alzheimers Dis 2015; 44: 215-231.

  • 21.

    Deplanque D, Gel P, Ptrault O, Six I, Furman C, Bouly M, et al. Peroxisome proliferator-activated receptor- activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment. J Neurosci 2003; 23: 6264-6271.

  • 22.

    Barbiero JK, Santiago RM, Persike DS, da Silva Fernandes MJ, Tonin FS, da Cunha C, et al. Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine. Behav Brain Res 2014; 274: 390-399.

  • 23.

    Watanabe Y, Kaida Y, Fukuhara S, Takechi K, Uehara T, Kamei C. Participation of metabotropic glutamate receptors in pentetrazolinduced kindled seizure. Epilepsia 2011; 52: 140-150.

  • 24.

    Malhi SM, Jawed H, Hanif F, Ashraf N, Zubair F, Siddiqui BS, et al. Modulation of c-Fos and BDNF protein expression in pentylenetetrazole-kindled mice following the treatment with novel antiepileptic compound HHL-6. Biomed Res Int 2014; 2014: 876712.

  • 25.

    De Silva DS, Wilson RM, Hutchinson C, Ip PC, Garcia AG, Lancel S, et al. Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms. Am J Physiol Heart Circ Physiol 2009; 296: H1983-1993.

  • 26.

    Schilling M, Wetzel W, Grecksch G, Becker A. Pentylenetetrazole kindling affects sleep in rats. Epilepsia 2006; 47: 2075-2082.

  • 27.

    Arjmand Abbassi Y, Mohammadi MT, Sarami Foroshani M, Raouf Sarshoori J. Captopril and valsartan may improve cognitive function through potentiation of the brain antioxidant defense system and attenuation of oxidative/nitrosative damage in STZ-Induced dementia in rat. Adv pharm bull 2016; 6: 531-539.

  • 28.

    Wjtowicz S, Strosznajder AK, Jeyna M, Strosznajder JB. The novel role of PPAR alpha in the brain: promising target in therapy of Alzheimer's disease and other neurodegenerative disorders. Neurochem Res 2020; 45: 972-988.

  • 29.

    Ogawa K, Yagi T, Guo T, Takeda K, Ohguchi H, Koyama H, et al. Pemafibrate, a selective PPAR modulator, and fenofibrate suppress microglial activation through distinct PPAR and SIRT1-dependent pathways. Biochem Biophys Res Commun 2020; 524: 385-391.

  • 30.

    Mohd Lazaldin MA, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, Mohd Ismail N. Neuroprotective effects of brainderived neurotrophic factor against amyloid beta 140induced retinal and optic nerve damage. Eur J Neurosci 2020; 51: 2394-2411.

  • 31.

    Kazmi Z, Zeeshan S, Khan A, Malik S, Shehzad A, Seo EK, et al. Anti-epileptic activity of daidzin in PTZ-induced mice model by targeting oxidative stress and BDNF/VEGF signaling. Neurotoxicology 2020; 79: 150-163.

  • 32.

    Lin TW, Harward SC, Huang YZ, McNamara JO. Targeting BDNF/TrkB pathways for preventing or suppressing epilepsy. Neuropharmacology 2020; 167: 107734.

  • 33.

    Panigrahy SR, Pradhan S, Maharana CS. Amelioration of oxidative Stress and neuroinflammation by saroglitazar, a dual PPAR/ agonist in MES induced epileptic rats. Biomed Pharmacol J 2019; 12: 1985-1991.

  • 34.

    de Souza AG, Chaves Filho AJ, Oliveira JV, de Souza DA, Lopes IS, de Carvalho MA, et al. Prevention of pentylenetetrazole-induced kindling and behavioral comorbidities in mice by levetiracetam combined with the GLP-1 agonist liraglutide: involvement of brain antioxidant and BDNF upregulating properties. Biomed Pharmacother 2019; 109: 429-439.

  • 35.

    Sarahian N, Mohammadi MT, Darabi S, Salem F. The effects of the peroxisome-proliferator activated receptor-alpha agonist, fenofibrate, on the antioxidant capacity of the brain in pentylenetetrazol kindling seizures in mice. React Oxyg Species (Apex) 2019; 7: 47-54,47-54.

  • 36.

    Ersan S, Cigdem B, Bakir D, Dogan HO. Determination of levels of oxidative stress and nitrosative stress in patients with epilepsy. Epilepsy Res 2020; 106352.

  • 37.

    Borowicz-Reutt KK, Czuczwar SJ. Role of oxidative stress in epileptogenesis and potential implications for therapy. Pharmacol Rep 2020; 72: 1218-1226.##.