The effect of silymarin on prevention of hippocampus neuronal damage in rats with temporal lob epilepsy

Document Type: Research Paper

Authors

1 Department of Anatomy and Pathology, School of Medicine, Shahed University, Tehran, Iran

2 School of Medicine, Shahed University, Tehran, Iran

3 Neurophysiology Research Center, Shahed University, Tehran, Iran

4 Department of Physiology, School of Medicine, Shahed University, Tehran, Iran

Abstract

Background and Objective: Temporal lobe epilepsy is hallmarked with neuronal degeneration in some areas of hippocampus and mossy fiber sprouting in dentate area. Considering some evidences on neuroprotective and antioxidant activity of silymarin (SM), this study was undertaken to evaluate the preventive effect of this agent on structural changes in hippocampus of kainate-epileptic rats.

Materials and Methods: In this study, 32 male rats were divided into sham, SM-treated sham, epileptic, and SM-treated epileptic group. Rat model of epilepsy was induced by unilateral intrahippocampal administration of 0.8 μg kainic acid per rat. Rats received SM (100 mg/kg, i.p.) daily for 3 days before the surgery. Finally, brain sections were stained with Nissl and Timm methods.

Results: Induction of epilepsy was followed by a significant seizure and SM pretreatment did not lower seizure intensity. In addition, density of Nissl-stained neurons in CA3 and CA4 areas of hippocampus was significantly lower in epileptic rats versus sham (p

Keywords


  1. Aminoff MJ, Simon RP. Status epilepticus. Causes, clinical features and consequences in 98 patients. American Journal of Medicine 1980;69(5):657-66.
  2. Chang BS, Lowenstein DH. Epilepsy. New England Journal of Medicine 2003;349(13):1257-66.
  3.  Engel J, Jr. Mesial temporal lobe epilepsy: what have we learned? Neuroscientist 2001;7(4):340-52.
  4. Kovac S, Domijan AM, Walker MC, Abramov AY. Seizure activity results in calcium- and mitochondria-independent ROS production via NADPH and xanthine oxidase activation. Cell Death & Disease 2014;5:e1442.
  5. Vezzani A, Ruegg S. The pivotal role of immunity and inflammatory processes in epilepsy is increasingly recognized: introduction. Epilepsia 2011;52 Suppl 3:1-4.
  6.  Ben-Ari Y, Cossart R. Kainate, a double agent that generates seizures: two decades of progress. Trends in Neurosciences 2000;23(11):580-7.
  7.  Kiasalari Z, Roghani M, Khalili M, Rahmati B, Baluchnejadmojarad T. Antiepileptogenic effect of curcumin on kainate-induced model of temporal lobe epilepsy. Pharmaceutical Biology 2013;51(12):1572-8.
  8.  Baluchnejadmojarad T, Roghani M. Coenzyme q10 ameliorates neurodegeneration, mossy fiber sprouting, and oxidative stress in intrahippocampal kainate model of temporal lobe epilepsy in rat. Journal of Molecular Neuroscience 2013;49(1):194-201.
  9.  Dariani S, Baluchnejadmojarad T, Roghani M. Thymoquinone attenuates astrogliosis, neurodegeneration, mossy fiber sprouting, and oxidative stress in a model of temporal lobe epilepsy. Journal of Molecular Neuroscience 2013;51(3):679-86.
  10.  Kiasalari Z, Khalili M, Shafiee S, Roghani M. The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats. Indian Journal of Pharmacology 2016;48(1):11-4.
  11.  Wieser HG. ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia 2004;45(6):695-714.
  12.  Si PP, Zhen JL, Cai YL, Wang WJ, Wang WP. Salidroside protects against kainic acid-induced status epilepticus via suppressing oxidative stress. Neuroscience Letters 2016;618:19-24.
  13.  Khamse S, Sadr SS, Roghani M, Hasanzadeh G, Mohammadian M. Rosmarinic acid exerts a neuroprotective effect in the kainate rat model of temporal lobe epilepsy: Underlying mechanisms. Pharmaceutical Biology 2015;53(12):1818-25.
  14.  Mandegary A, Saeedi A, Eftekhari A, Montazeri V, Sharif E. Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-alpha cytokine genetic polymorphism. Daru 2013;21(1):28.
  15.  Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB. Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. Journal of Immunology 1999;163(12):6800-9.
  16.  Gupta OP, Sing S, Bani S, Sharma N, Malhotra S, Gupta BD, et al. Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine 2000;7(1):21-4.
  17.  Baluchnejadmojarad T, Roghani M, Mafakheri M. Neuroprotective effect of silymarin in 6-hydroxydopamine hemi-parkinsonian rat: involvement of estrogen receptors and oxidative stress. Neuroscience Letters 2010;480(3):206-10.
  18.  Haddadi R, Mohajjel Nayebi A, Brooshghalan SE. Pre-treatment with silymarin reduces brain myeloperoxidase activity and inflammatory cytokines in 6-OHDA hemi-parkinsonian rats. Neuroscience Letters 2013;555:106-11.
  19.  Haddadi R, Nayebi AM, Farajniya S, Brooshghalan SE, Sharifi H. Silymarin improved 6-OHDA-induced motor impairment in hemi-parkisonian rats: behavioral and molecular study. Daru 2014;22:38.
  20.  Hirayama K, Oshima H, Yamashita A, Sakatani K, Yoshino A, Katayama Y. Neuroprotective effects of silymarin on ischemia-induced delayed neuronal cell death in rat hippocampus. Brain Research 2016;1646:297-303.
  21.  Perez HJ, Carrillo SC, Garcia E, Ruiz-Mar G, Perez-Tamayo R, Chavarria A. Neuroprotective effect of silymarin in a MPTP mouse model of Parkinson's disease. Toxicology 2014;319:38-43.
  22.  Lang I, Deak G, Muzes G, Pronai L, Feher J. Effect of the natural bioflavonoid antioxidant silymarin on superoxide dismutase (SOD) activity and expression in vitro. Biotechnology Therapeutics 1993;4(3-4):263-70.
  23.  Wang MJ, Lin WW, Chen HL, Chang YH, Ou HC, Kuo JS, et al. Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. European Journal of Neuroscience 2002;16(11):2103-12.
  24.  Raza SS, Khan MM, Ashafaq M, Ahmad A, Khuwaja G, Khan A, et al. Silymarin protects neurons from oxidative stress associated damages in focal cerebral ischemia: a behavioral, biochemical and immunohistological study in Wistar rats. Journal of the Neurological Sciences 2011;309(1-2):45-54.
  25.  Hou YC, Liou KT, Chern CM, Wang YH, Liao JF, Chang S, et al. Preventive effect of silymarin in cerebral ischemia-reperfusion-induced brain injury in rats possibly through impairing NF-kappaB and STAT-1 activation. Phytomedicine 2010;17(12):963-73.
  26. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 2nd ed., Academic Press 1986;San Diego.
  27.  Racine R, Okujava V, Chipashvili S. Modification of seizure activity by electrical stimulation. 3. Mechanisms. Electroencephalography and Clinical Neurophysiology 1972;32(3):295-9.
  28.  Karoly N, Mihaly A, Dobo E. Comparative immunohistochemistry of synaptic markers in the rodent hippocampus in pilocarpine epilepsy. Acta Histochemica 2011;113(6):656-62.
  29.  Wu Z, Xu Q, Zhang L, Kong D, Ma R, Wang L. Protective effect of resveratrol against kainate-induced temporal lobe epilepsy in rats. Neurochemical Research 2009;34(8):1393-400.
  30.  Sharma AK, Reams RY, Jordan WH, Miller MA, Thacker HL, Snyder PW. Mesial temporal lobe epilepsy: pathogenesis, induced rodent models and lesions. Toxicologic Pathology 2007;35(7):984-99.
  31.  Sperk G. Kainic acid seizures in the rat. Progress in Neurobiology 1994;42(1):1-32.
  32.  Liu K, Peterson KL, Raboy V. Comparison of the phosphorus and mineral concentrations in bran and abraded kernel fractions of a normal barley (Hordeum vulgare) cultivar versus four low phytic acid isolines. Journal of Agricultural and Food Chemistry 2007;55(11):4453-60.
  33.  Weber LP, Chow WL, Abebe W, MacLeod KM. Enhanced contractile responses of arteries from streptozotocin diabetic rats to sodium fluoride. British Journal of Pharmacology 1996;118(1):115-22.
  34.  Shetty AK, Hattiangady B. Restoration of calbindin after fetal hippocampal CA3 cell grafting into the injured hippocampus in a rat model of temporal lobe epilepsy. Hippocampus 2007;17(10):943-56.