Sains Malaysiana 53(3)(2024): 561-573
http://doi.org/10.17576/jsm-2024-5303-07
Nigella sativa Supplementation
Attenuates Recognition Memory and Cellular Morphometric Impairments Induced by
Toluene Administration in Mice
(Suplemen Nigella sativa Melemahkan Ingatan Pengecaman dan Kemerosotan Sel Morfometri Aruhan Pemberian Toluena kepada Mencit)
NUR
LISA MOHD YUSOFF1, DURRIYYAH SHARIFAH HASAN ADLI2 &
SHEENA YIN XIN TIONG1,*
1Institute of Biological Sciences,
Faculty of Science, Universiti Malaya, 50603
Kuala
Lumpur, Malaysia
2Centre for Civilisational Dialogue, Universiti Malaya, 50603 Kuala Lumpur,
Malaysia
Received: 5 July 2023/Accepted: 9 February 2024
Abstract
Toluene exposure has been
associated with detrimental effects on the central nervous system. Discovering
natural products that can offer neuroprotection following toluene exposure is
an essential alternative. Nigella sativa (NS), a popular natural
supplement, is a good candidate due to its antioxidant and neuroprotective
properties. The study aimed to investigate the protective potentials of NS
against toluene, on recognition memory performance in the Novel Object
Recognition (NOR) test and cellular morphometric measurements of hippocampal
CA1 pyramidal neurons. Adult male ICR mice (n=30) were randomly divided into five
groups: Group 1 (G1) - corn oil (CO), G2 – Toluene (TOL), G3 - Toluene and NS
seed suspension (TOL-NSS), G4 - Toluene and NS oil (TOL-NSO), G5 - Toluene and thymoquinone (TOL-TQ). NS supplementations were
administered orally once daily for 14 consecutive days while 500 mg/kg b.w. toluene was administered intraperitoneally from day 8 until
day 14. Behavioural NOR test was conducted.
Subsequently, mice were intracardially perfused and
harvested brains were histologically processed. The somatic size and shape of
hippocampal CA1 pyramidal neurons were quantified according to specific
morphometric parameters. Toluene reduced recognition memory performance of mice
and somatic size of hippocampal CA1 pyramidal neurons. Contradictorily, TQ,
NSO, and NSS improved mice recognition memory and somatic size of hippocampal
CA1 pyramidal neurons. Somatic shape of hippocampal CA1 pyramidal was
unaffected by the various treatments. Although non-significant differences were
observed, the results indicate the tendency for toluene to cause impairment,
while NS supplementations to improve mice recognition memory performance and
brain hippocampal neuron structure.
Keywords: Brain morphology; Nigella
sativa; recognition memory; somatic morphometry; toluene
Abstrak
Pendedahan kepada toluena telah dikaitkan dengan kesan buruk pada sistem saraf pusat. Pencarian bahan semula jadi yang boleh menawarkan perlindungan saraf berikutan pendedahan toluena adalah alternatif yang penting. Nigella sativa (NS), suplemen semula jadi yang popular, adalah calon yang baik kerana mempunyai ciri antioksida serta berpotensi melindungi sistem saraf. Penyelidikan ini bertujuan untuk mengkaji potensi perlindungan NS melalui prestasi ingatan pengecaman dalam ujian Pengecaman Objek Novel (NOR) dan pengukuran morfometrik sel CA1 neuron piramid hipokampus. Tikus ICR jantan dewasa (n=30) dibahagikan secara rawak kepada lima kumpulan: Kumpulan 1 (G1) - minyak jagung (CO), G2 - Toluena (TOL), G3 - Toluena dan biji NS (TOL-NSS), G4 - Toluena dan minyak NS (TOL-NSO), G5 - Toluena dan thymoquinone (TOL-TQ). Suplemen NS diberikan secara oral sekali sehari selama 14 hari berturut-turut manakala 500 mg/kg b.w. toluena diberikan secara intraperitoneal dari hari ke-8 hingga hari ke-14. Ujian NOR tingkah laku telah dijalankan. Selepas itu, perfusi intrakardiak dilakukan ke atas mencit dan otak yang dituai diproses secara histologi. Saiz dan bentuk somatik CA1 neuron piramid hipokampus dihitung mengikut parameter morfometrik tertentu. Toluena mengurangkan prestasi ingatan pengecaman mencit dan saiz somatik CA1 neuron piramid hipokampus. Sebaliknya, TQ, NSO dan NSS meningkatkan ingatan pengecaman tikus dan saiz somatik CA1 neuron piramid hipokampus. Bentuk somatik CA1 neuron piramid hipokampus tidak terjejas oleh pelbagai rawatan tersebut. Walaupun perbezaan yang tidak ketara dapat diperhatikan, keputusan menunjukkan kecenderungan toluena untuk menyebabkan kemerosotan, manakala suplemen NS untuk meningkatkan prestasi ingatan pengecaman mencit dan struktur neuron hipokampus otak.
Kata kunci: Ingatan pengecaman; morfologi otak; morfometri soma; Nigella sativa; toluene
REFERENCES
Abdel-Salam,
O.M.E., Sleem, A.A. & Morsy,
F.A. 2020. Citric acid protects against toluene-induced brain neurodegeneration
and liver damage in rats. Journal of Basic Pharmacology and Toxicology 4(2): 38-48.
Abdel-Salam,
O.M.E., El-Shamarka, M.E.-S., Hassan, N.S. & Abouelfadl, D.M. 2021. Effect of piracetam on brain oxidative stress and tissue damage following toluene exposure in rats. International Journal of Halal Research 3(1): 8-23.
https://doi.org/10.18517/ijhr.3.1.8-23.2021
Abouee-Mehrizi,
A., Rasoulzadeh, Y., Mesgari-Abbasi,
M., Mehdipour, A. & Ebrahimi-Kalan,
A. 2020. Nephrotoxic effects caused by co-exposure to noise and toluene in New
Zealand white rabbits: A biochemical and histopathological study. Life
Sciences 259: 118254.
https://doi.org/https://doi.org/10.1016/j.lfs.2020.118254
Ahmad, A., Husain, A., Mujeeb, M., Khan, S.A., Najmi, A.K.,
Siddique, N.A., Damanhouri, Z.A. & Anwar, F. 2013. A review on therapeutic
potential of Nigella sativa: A miracle herb. Asian Pacific Journal of
Tropical Biomedicine 3(5): 337-352. https://doi.org/10.1016/S2221-1691(13)60075-1
Alhebshi, A.H., Odawara, A., Gotoh, M. & Suzuki, I. 2014.
Thymoquinone protects cultured hippocampal and human induced pluripotent stem
cells-derived neurons against α-synuclein-induced synapse damage. Neuroscience
Letters 570: 126-131. https://doi.org/10.1016/j.neulet.2013.09.049
Al-Nailey, K.G.C. 2010.
Study of the protective effect of Nigella sativa against Cimetidine
induced reproductive toxicity in male mice. Al-Qadisiyah Journal of
Veterinary Medicine Sciences 9(1): 55-62.
Armenta-Reséndiz, M., Ríos-Leal, E., Rivera-García, M.T.,
López-Rubalcava, C. & Cruz, S.L. 2019. Structure-activity study of acute
neurobehavioral effects of cyclohexane, benzene, m-xylene, and toluene in rats. Toxicology and Applied Pharmacology 376: 38-45. https://doi.org/10.1016/j.taap.2019.05.016
Asrar, B., Ikram, U.K., Homberg, J.R. & Haleem, D.J.
2020. Nigella sativa oil ameliorates chronic ethanol induced anxiety and
impaired spatial memory by modulating noradrenaline levels. Pakistan
Veterinary Journal 40(3): 350-354.
Ayu, P.S., Tualeka, A.R., Arini, S.Y., Russeng, S.S.,
Rahmawati, P., Ahsan, A. & Susilowati, I.H. 2020. Relationship between
toluene concentration, malondialdehyde (MDA) level and health complaints in
workers of Surabaya printing industry. Indian Journal of Forensic Medicine
& Toxicology 14(4): 3389-3395.
Azaizeh, H., Saad, B., Cooper, E. & Said, O. 2010.
Traditional Arabic and Islamic medicine, a re-emerging health aid. Evidence-Based Complementary and
Alternative Medicine 7(4): 419-424. https://doi.org/10.1093/ecam/nen039
Baghani, A.N., Sorooshian, A., Heydari, M., Sheikhi, R.,
Golbaz, S., Ashournejad, Q., Kermani, M., Golkhorshidi, F., Barkhordari, A.,
Jafari, A.J., Delikhoon, M. & Shahsavani, A. 2019. A case study of BTEX
characteristics and health effects by major point sources of pollution during
winter in Iran. Environmental Pollution 247: 607-617.
https://doi.org/10.1016/j.envpol.2019.01.070
Baghcheghi, Y., Hosseini, M., Beheshti, F., Salmani, H. &
Anaeigoudari, A. 2018. Thymoquinone reverses learning and memory impairments
and brain tissue oxidative damage in hypothyroid juvenile rats. Arquivos de
Neuro-Psiquiatria 76(1): 32-40. https://doi.org/10.1590/0004-282X20170182
Balbaa, M., Abdulmalek, S.A. & Khalil, S. 2017. Oxidative
stress and expression of insulin signaling proteins in the brain of diabetic
rats: Role of Nigella sativa oil and antidiabetic drugs. PLoS ONE 12(5): 1-23. https://doi.org/10.1371/journal.pone.0172429
Bargi, R., Asgharzadeh, F., Beheshti, F., Hosseini, M.,
Sadeghnia, H.R. & Khazaei, M. 2017.
The effects of thymoquinone on hippocampal cytokine level, brain oxidative
stress status and memory deficits induced by lipopolysaccharide in rats. Cytokine 96: 173-184. https://doi.org/10.1016/j.cyto.2017.04.015
Beheshti, F., Hosseini, M., Vafaee, F., Shafei, M.N. &
Soukhtanloo, M. 2016. Feeding of Nigella sativa during neonatal and
juvenile growth improves learning and memory of rats. Journal of Traditional
and Complementary Medicine 6(2): 146-152. https://doi.org/10.1016/j.jtcme.2014.11.039
Ben-Shaul, Y. 2017. OptiMouse: A comprehensive open source
program for reliable detection and analysis of mouse body and nose positions. BMC
Biology 15(1): 1-22. https://doi.org/10.1186/s12915-017-0377-3
Billeci, L., Magliaro, C., Pioggia, G. & Ahluwalia, A.
2013. NEuronMOrphological analysis tool: Open-source software for quantitative
morphometrics. Frontiers in Neuroinformatics 7: 2. doi:
10.3389/fninf.2013.00002
Braunscheidel, K.M., Okas, M.P., Hoffman, M., Mulholland,
P.J., Floresco, S.B. & Woodward, J.J. 2019. The abused inhalant toluene
impairs medial prefrontal cortex activity and risk/reward decision-making
during a probabilistic discounting task. Journal of Neuroscience 39(46):
9207-9220. https://doi.org/10.1523/JNEUROSCI.1674-19.2019
Chan, M., Austen, J.M., Eacott, M.J., Easton, A. &
Sanderson, D.J. 2019. The NMDA receptor antagonist MK-801 fails to impair
long-term recognition memory in mice when the state-dependency of memory is
controlled. Neurobiology of Learning and Memory 161: 57-62.
Cheema, M.A.R., Nawaz, S., Gul, S., Salman, T., Naqvi, S.,
Dar, A. & Haleem, D.J. 2018. Neurochemical and behavioral effects of Nigella
sativa and Olea europaea oil in rats. Nutritional Neuroscience 21(3): 185-194. https://doi.org/10.1080/1028415X.2016.1257417
Cruz, S.L., Torres-Flores, M. & Galván, E.J. 2019.
Repeated toluene exposure alters the synaptic transmission of layer 5 medial
prefrontal cortex. Neurotoxicology and Teratology 73(235): 9-14.
https://doi.org/10.1016/j.ntt.2019.02.002
Demır, M., Cicek, M., Eser, N., Yoldaş, A. &
Sısman, T. 2017. Effects of acute toluene toxicity on different regions of
rabbit brain. Analytical Cellular Pathology 2017: 2805370.
https://doi.org/10.1155/2017/2805370
Denninger, J.K., Smith, B.M. & Kirby, E.D. 2018. Novel
object recognition and object location behavioral testing in mice on a budget. Journal of Visualized Experiments: 141: e58593.
https://doi.org/10.3791/58593
Dick, A.L.W., Zhao, Q., Crossin, R., Baker-Andresen, D., Li,
X., Edson, J., Roeh, S., Marshall, V., Bredy, T.W., Lawrence, A.J. &
Duncan, J.R. 2021. Adolescent chronic intermittent toluene inhalation
dynamically regulates the transcriptome and neuronal methylome within the rat
medial prefrontal cortex. Addiction Biology 26(3): e12937.
Duncan, J.R., Dick, A.L.W., Egan, G., Kolbe, S., Gavrilescu,
M., Wright, D., Lubman, D.I., & Lawrence, A.J. 2012. Adolescent toluene
inhalation in rats affects white matter maturation with the potential for
recovery following abstinence. PLoS ONE 7(9): e44790.
El-Safti, F.E., El-Kholoy,
W.B., El-Mehi, A.E. & Selima,
R.R. 2017. A comparative study on the effect of aging on the hippocampal CA1
area of male albino rat. Menoufia Med. J 30: 1079-1084.
Fanoudi, S., Alavi, M.S., Hosseini, M. & Sadeghnia, H.R.
2019. Nigella sativa and thymoquinone attenuate oxidative stress and
cognitive impairment following cerebral hypoperfusion in rats. Metabolic
Brain Disease 34: 1001-1010.
Gospe Jr., S.M. & Zhou, S.S. 2000. Prenatal exposure to
toluene results in abnormal neurogenesis and migration in rat somatosensory
cortex. Pediatric Research 47(3): 362-368.
Hossain, M.S., Sharfaraz, A., Dutta, A.S., Ahsan, A., Masud,
M.A., Ahmed, I.A., Goh, B., Urbi, Z., Sarker, M.M. & Ming, L.C. 2021. A
review of ethnobotany, phytochemistry, antimicrobial pharmacology and
toxicology of Nigella sativa L. Biomedicine and Pharmacotherapy 143: 112182. https://doi.org/10.1016/j.biopha.2021.112182
Hsieh, C.P., Chen, H., Chan, M.H., Chen, L. & Chen, H.H.
2020. N,N-dimethylglycine prevents toluene-induced impairment in recognition
memory and synaptic plasticity in mice. Toxicology 446: 152613.
Huang, T. & Hsueh, Y. 2014. Novel object recognition for
studying memory in mice. Bio-Protocol 4(19): e1249.
https://doi.org/10.21769/BioProtoc.1249
Huerta-Rivas, A., López-Rubalcava, C., Sánchez-Serrano, S.L.,
Valdez-Tapia, M., Lamas, M. & Cruz, S.L. 2012. Toluene impairs learning and
memory, has antinociceptive effects, and modifies histone acetylation in the
dentate gyrus of adolescent and adult rats. Pharmacology Biochemistry and
Behavior 102(1): 48-57.
Hussien, N.I., Elawady, M.A., Elmaghrabi, M.M. &
Muhammad, M.H. 2020. Impact of thymoquinone on memory deficit-associated with
global cerebral ischemia-reperfusion injury in rats: Possible role of
PPAR-γ. American Journal of Biomedical Sciences 12(1): 77-90.
Kantachai, P., Kaewkaen, P. & Janthakhin, Y. 2020. The
analysis of toluene concentrations affecting learning and long-term memory of
mice and workers who long-term exposed to low-level of toluene. Research
Methodology and Cognitive Science 17(2): 69-82.
Khazdair, M.R., Anaeigoudari, A., Hashemzehi, M. &
Mohebbati, R. 2019. Neuroprotective potency of some spice herbs, a literature
review. Journal of Traditional and Complementary Medicine 9(2): 98-105.
https://doi.org/10.1016/j.jtcme.2018.01.002
Lee, M.Y., Lin, B.F., Chan, M.H. & Chen,
H.H. 2020. Increased behavioral and neuronal responses to a
hallucinogenic drug after adolescent toluene exposure in mice: Effects of
antipsychotic treatment. Toxicology 445: 152602.
ttps://doi.org/10.1016/j.tox.2020.152602
Liu, J., Chang, L., Song, Y., Li, H. & Wu, Y. 2019. The
role of NMDA receptors in Alzheimer’s disease. Frontiers in Neuroscience 13: 43. https://doi.org/10.3389/fnins.2019.00043
Luengo-Sanchez, S., Bielza, C., Benavides-Piccione, R.,
Fernaud-Espinosa, I., Defelipe, J. & Larrañaga, P. 2015. A univocal
definition of the neuronal soma morphology using gaussian mixture models. Frontiers
in Neuroanatomy 9: 137.
Meira, T., Leroy, F., Buss, E.W., Oliva, A., Park, J. &
Siegelbaum, S.A. 2018. A hippocampal circuit linking dorsal CA2 to ventral CA1
critical for social memory dynamics. Nature Communications 9(1): 4163.
https://doi.org/10.1038/s41467-018-06501-w
Meitzen, J., Pflepsen, K.R., Stern, C.M., Meisel, R.L. &
Mermelstein, P.G. 2011. Measurements of neuron soma size and density in rat
dorsal striatum, nucleus accumbens core and nucleus accumbens shell:
Differences between striatal region and brain hemisphere, but not sex. Neuroscience
Letters 487(2): 177-181. https://doi.org/10.1016/j.neulet.2010.10.017
Meydan, S., Altas, M., Nacar, A., Ozturk, O.H., Tas, U.,
Zararsiz, I. & Sarsilmaz, M. 2012. The protective effects of omega-3 fatty
acid against toluene-induced neurotoxicity in prefrontal cortex of rats. Human
and Experimental Toxicology 31(11): 1179-1185.
Moawad, R., Abd El Fattah, E. & Alsemeh, A. 2021.
Deleterious effect of toluene on rat cerebrum cortex and the exert effect of
resveratrol: (Histological, immunohistochemical and ultrastructural study). Egyptian
Journal of Histology 44(3): 855-872. doi: 10.21608/ejh.2021.71825.1459
Montes, S., Solís-Guillén, R.D.C., García-Jácome, D. &
Páez-Martínez, N. 2017. Environmental enrichment reverses memory impairment
induced by toluene in mice. Neurotoxicology and Teratology 61: 7-16.
https://doi.org/10.1016/j.ntt.2017.04.003
Paramo, B., Bachmann, S.O., Baudouin, S.J., Martinez-Garay,
I. & Davies, A.M. 2021. Neuregulin-4 is required for maintaining soma size
of pyramidal neurons in the motor cortex. eNeuro 8(1):
ENEURO.0288-20.2021. https://doi.org/10.1523/ENEURO.0288-20.2021
Sahak, M.K.A., Kabir, N., Abbas, G., Draman, S., Hashim, N.H.
& Hasan Adli, D.S. 2016. The role of Nigella sativa and its active
constituents in learning and memory. Evidence-Based Complementary and
Alternative Medicine 2016: 6075679. https://doi.org/10.1155/2016/6075679
Salem, R.R. & Kelada, M.N.B. 2020. A biochemichal and
ultrastructural study on the effect of toluene on the pars distalis of anterior
pituitary glands of adult male albino rats. Egyptian Journal of Histology 43(3): 948-959. https://doi.org/10.21608/ejh.2020.21574.1222
Sathe, S., Chan, X.Q., Jin, J., Bernitt, E., Döbereiner, H.G.
& Yim, E.K.F. 2017. Correlation and comparison of cortical and hippocampal
neural progenitor morphology and differentiation through the use of micro- and
nano-topographies. Journal of Functional Biomaterials 8(3): 35.
https://doi.org/10.3390/jfb8030035
Seo, H.S., Yang,
M., Song, M.S., Kim, J.S., Kim, S.H., Kim, J.C., Kim, H., Shin, T., Wang, H.
& Moon, C. 2010. Toluene inhibits hippocampal neurogenesis in adult mice. Pharmacology
Biochemistry and Behavior 94(4): 588-594.
https://doi.org/10.1016/j.pbb.2009.11.015
Shaffie, N. & Shabana, M. 2019. Role of citicoline as a
protective agent on toluene-induced toxicity in rats. Journal of the
Arab Society of Medical Research 14(1): 14.
Soares, M.V., Charão, M.F., Jacques, M.T., Dos Santos,
A.L.A., Luchese, C., Pinton, S. & Ávila, D.S. 2020. Airborne toluene
exposure causes germline apoptosis and neuronal damage that promotes
neurobehavioural changes in Caenorhabditis elegans. Environmental
Pollution 256: 113406. https://doi.org/10.1016/J.ENVPOL.2019.113406
Tahmasebi, S., Oryan, S., Mohajerani, H.R., Akbari, N. &
Palizvan, M.R. 2020. Probiotics and Nigella sativa extract
supplementation improved behavioral and electrophysiological effects of
PTZ-induced chemical kindling in rats. Epilepsy and Behavior 104:
106897. https://doi.org/10.1016/j.yebeh.2019.106897
Toktam, M., Mahmood, H., Reza, K., Mohammad, S. & Ziba,
R. 2011. The acetylcholine esterase activity inhibition as a possible mechanism
for beneficial effects of Nigella sativa on memory. Clinical
Biochemistry 44(13): S349.
https://doi.org/10.1016/j.clinbiochem.2011.08.872
Tong, L., Langton, R., Glykys, J. & Baek, S. 2021. ANMAF:
An automated neuronal morphology analysis framework using convolutional neural
networks. Scientific Reports 11(1): 8179.
https://doi.org/10.1038/s41598-021-87471-w
Umukoro, S., Apara, M., Ben-Azu, B., Ajayi, A.M. &
Aderibigbe, A.O. 2021. Neurobehavioral effects of prolonged exposure to solid
air freshener in mice. Iranian Journal of Toxicology 13(3): 45-51.
Werder, E.J., Engel, L.S., Blair, A., Kwok, R.K., McGrath,
J.A. & Sandler, D.P. 2019. Blood BTEX levels and neurologic symptoms in Gulf
states residents. Environmental Research 175: 100-107.
https://doi.org/10.1016/j.envres.2019.05.004
Win-Shwe, T.T. & Fujimaki, H. 2012. Acute administration
of toluene affects memory retention in novel object recognition test and memory
function-related gene expression in mice. Journal of Applied Toxicology 32(4): 300-304. https://doi.org/10.1002/jat.1693
Win-Shwe, T.T., Kunugita, N., Yoshida, Y., Nakajima, D.,
Tsukahara, S. & Fujimaki, H. 2012. Differential mRNA expression of
neuroimmune markers in the hippocampus of infant mice following toluene
exposure during brain developmental period. Journal of Applied Toxicology 32(2): 126-134. https://doi.org/10.1002/jat.1643
Wu, C.Y., Tsai, Y.L., Hsieh, C.P., Wang, T.C., Chan, M.H.
& Chen, H.H. 2018. Attenuation of toluene-induced brain stimulation reward
enhancement and behavioral disturbances by N-acetylcysteine in mice. Toxicology 408: 39-45. https://doi.org/10.1016/j.tox.2018.06.011
*Corresponding author;
email: stiong@um.edu.my
|