The effect of silymarin on memory and learning disorders induced by TiO2 nanoparticles

Authors

Abstract

Background and Objective: Titanium dioxide nanoparticles (NP Tio2) are one of the most highly used particles in the world. They are used for biomedical and cosmetic goals. Several studies have shown that NP Tio2 induce oxidative stress in the hippocampus. Silymarin is a flavenolignan that is gained from seed of milk thistle (Silybum marianum) and due to its inhibition of free radicals, acts as an antioxidant in central nerves system. Aim of this research was to study the effect of silymarin on memory and learning disorders induced by TiO2 nanoparticles.
 
Materials and Methods: In this experimental study, rats were divided into four groups: control, vehicle, toxic group (150 mg/kg of TiO2 NPs for three weeks orally) as well as silymarin (100 mg/kg for three weeks orally after TiO2 NPs administration). The destructive effect of Nano TiO2 and treatment with silymarin were measured by passive avoidance test using shuttle box.
 
Results: Oral administration of Tio2 NPs resulted in a significant increase of time of spending in dark box and reduction of time to enter the dark box and silymarin significantly decreased time of spending in dark box (P > 0.001) and treatment with silymarin returned the index to the level of control (P > 0.001). 
 
Conclusion: The results from the present study indicated that silymarin probably due to its antioxidant effects causes improvement of memory and learning disorders induced by TiO2 nanoparticles.
 

Keywords


1. Iavicoli I, Leso VE, Fontana LU, Bergamaschi A. Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies. Eur Rev Med Pharmacol Sci. 2011; 5: 481-508. 2. Sheng L, Wang X, Sang X, Ze Y, Zhao X, Liu D, Gui S, Sun Q, Cheng J, Cheng Z, Hu R. Cardiac oxidative damage in mice following exposure to nanoparticulate titanium dioxide. Journal of Biomedical Materials Research Part A. 2013; 11: 3238-46. 3. Gao X, Yin S, Tang M, Chen J, Yang Z, Zhang W, Chen L, Yang B, Li Z, Zha Y, Ruan D. Effects of developmental exposure to TiO2 nanoparticles on synaptic plasticity in hippocampal dentate gyrus area: an in vivo study in anesthetized rats. Biological trace element research. 2011; 3: 1616-28. 4. Wang J, Liu Y, Jiao F, Lao F, Li W, Gu Y, Li Y, Ge C, Zhou G, Li B, Zhao Y. Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO 2 nanoparticles. Toxicology. 2008; 1: 82-90. 5. Hu R, Zheng L, Zhang T, Gao G, Cui Y, Cheng Z, Cheng J, Hong M, Tang M, Hong F. Molecular mechanism of hippocampal apoptosis of mice following exposure to titanium dioxide nanoparticles. Journal of hazardous materials. 2011; 1: 32-40. 6. Sheng L, Ze Y, Wang L, Yu X, Hong J, Zhao X, Ze X, Liu D, Xu B, Zhu Y, Long Y. Mechanisms of TiO2 nanoparticle‐induced neuronal apoptosis in rat primary cultured hippocampal neurons. Journal of Biomedical Materials Research Part A. 2015; 3: 1141-9. 7. Schacter DL, Verfaellie M, Koutstaal W. Memory illusions in amnesic patients: Findings and implications. Guilford Press 2002. 8. Shahbazi R, Davoodi H, Esmaeili S.‎ Iranian Journal of Nutrition Sciences & Food Technology 2013; 7[Text in Persian] 9. Javed S, Kohli K, Ali M. Reassessing bioavailability of silymarin. Altern Med Rev. 2011; 3: 239-49. 10. Jameel.N Z, Haider.JA, Taha.Y. Synthesis of TiO2 Nan particles by Using Sol-Gel Method and its Applications as Antibacterial Agents.Eng & Tech.Journal, 2014; 3. 11. Nikkhah A, Ghahremanitamadon F, Zargooshnia S, Shahidi S, Asl SS. Effect of Amyloid β-Peptide on Passive Avoidance Learning in Rats: A Behavioral Study. Avicenna Journal of Neuro Psych Physiology. 2014; 1 12. Lashgari R, Motamedi F, Asl SZ, Shahidi S, Komaki A. Behavioral and electrophysiological studies of chronic oral administration of L-type calcium channel blocker verapamil on learning and memory in rats. Behavioural brain research. 2006; 2: 324-8. 13. Shahidi S, Komaki A, Mahmoodi M, Atrvash N, Ghodrati M. Ascorbic acid supplementation could affect passive avoidance learning and memory in rat. Brain research bulletin. 2008; 1: 109-13. 14. Yaghmaei P, Azarfar K, Dezfulian M, Ebrahim-Habibi A. Silymarin effect on amyloid-β plaque accumulation and gene expression of APP in an Alzheimer’s disease rat model. DARU Journal of Pharmaceutical Sciences. 2014; 1: 1. 15. Liu S, Xu L, Zhang T, Ren G, Yang Z. Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12 cells. Toxicology. 2010; 1: 172-7. 16. Ma L, Liu J, Li N, Wang J, Duan Y, Yan J, Liu H, Wang H, Hong F. Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO 2 delivered to the abdominal cavity. Biomaterials. 2010; 1: 99-105. 17. Meena R, Kumar S, Paulraj R. Titanium oxide (TiO2) nanoparticles in induction of apoptosis and inflammatory response in brain. Journal of Nanoparticle Research. 2015; 1: 1-4. 18. Ze Y, Sheng L, Zhao X, Ze X, Wang X, Zhou Q, Liu J, Yuan Y, Gui S, Sang X, Sun Q. Neurotoxic characteristics of spatial recognition damage of the hippocampus in mice following subchronic peroral exposure to TiO 2 nanoparticles. Journal of hazardous materials. 2014; 264: 219-29. 19. Borah A, Paul R, Choudhury S, Choudhury A, Bhuyan B, Das Talukdar A, Dutta Choudhury M, Mohanakumar KP. Neuroprotective potential of silymarin against CNS disorders: insight into the pathways and molecular mechanisms of action. CNS neuroscience & therapeutics. 2013; 11: 847-53. 20. Patten A, Brocardo PS, Gil-Mohapel J, Christie BR. Oxidative Stress in Fetal Alcohol Spectrum Disorders–Insights for the Development of Antioxidant-Based Therapies. InSystems Biology of Free Radicals and Antioxidants . Springer Berlin Heidelberg. 2014; 645-667 21. Kang JS, Jeon YJ, Kim HM, Han SH, Yang KH. Inhibition of inducible nitric-oxide synthase expression by silymarin in lipopolysaccharide-stimulated macrophages. Journal of Pharmacology and Experimental Therapeutics. 2002; 1: 138-44. 22. Yaghmaei PA, Parivar KA, Darab M, Oryan SH, Abbasi ES. The effect of Silymarin on learning and histological changes of hippocampal regions of rats. J Qazvin Univ Med Sci. 2010; 3: 25-30. 23. Yaghmaei P, Parivar K, Masoudi A, Darab M, Amini E. The effect of silybin on passive avoidance learning and pathological changes in hippocampal CA1 and DG regions in male Wistar rats offspring. Journal of Asian natural products research. 2009; 6: 514-22. 24. 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.