Abstract
The aim of this study was designed to investigate the possible beneficial effects of Nigella sativa (NS) and derived thymoquinone (TQ) on neurodegeneration in hippocampus after chronic toluene exposure in rats. The rats were randomly allotted into one of four experimental groups: A (control), B (toluene treated), C (toluene treated with NS) and D (toluene treated with TQ); each group contain 10 animals. Toluene treatment was performed by inhalation of 3,000 ppm toluene, in a 8 h/day and 6 day/week order for 12 weeks. Control group received 1 ml serum physiologic and the rats in NS and TQ treated groups (C and D) were given NS (in a dose of 400 mg/kg body weight) and TQ (50 mg/kg body weight) once a day orally by using intra gastric intubation for 12 weeks starting just after toluene exposure respectively. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in hippocampus after chronic toluene exposure in rats by NS and TQ treatment have been reported. In this study, chronic toluene exposure caused severe degenerative changes, shrunken cytoplasma, slightly dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the hippocampus. The distorted nerve cells were mainly absent in the TQ and NS-treated rats. We conclude that TQ and especially NS therapy causes morphologic improvement on neurodegeneration in hippocampus after chronic toluene exposure in rats. We believe that further preclinical research into the utility of NS and TQ may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats.
Similar content being viewed by others
References
Kurtzman TL, Otsuka KN, Wahl RA (2001) Inhalant abuse by adolescents. J Adolesc Health 28:170–180
Evans EB, Balster RL (1991) CNS depressant effects of volatile organic solvents. Neurosci Biobehav Rev 15:233–241
Flanagan RJ, Ruprah M, Meredith TJ, Ramsey JD (1990) An introduction to the clinical toxicology of volatile substances. Drug Saf 5:359–383
Kjellstrand P, Holmquist B, Jonsson I, Romare S, Mansson L (1985) Effects of organic solvents on motor activity in mice. Toxicol 35:35–46
Kondo H, Huang J, Ichihara G, Kamijima M, Saito I, Shibata E, Ono Y, Hisanaga N, Takeuchi Y, Nakahara D (1995) Toluene induces behavioral activation without affecting striatal dopamine metabolism in the rat: behavioral and microdialysis studies. Pharmacol Biochem Behav 51:97–101
Riegel AC, French ED (1999) Acute toluene induces biphasic changes in rat spontaneous locomotor activity which are blocked by remoxipride. Pharmacol Biochem Behav 62:399–402
Wiaderna D, Tomas T (2000) Effects of repeated exposure to toluene or amphetamine on locomotor activity in rats. Int J Occup Med Environ Health 13:317–324
Wood RW, Colotla VA (1990) Biphasic changes in mouse motor activity during exposure to toluene. Fundam Appl Toxicol 14:6–14
von Euler M, Pham TM, Hillefors M, Bjelke B, Henriksson B, von Euler G (2000) Inhalation of low concentrations of toluene 7induces persistent effects on a learning retention task, beam-walk performance, and cerebrocortical size in the rat. Exp Neurol 163:1–8
Beyer CE, Stafford D, LeSage MG, Glowa JR, Steketee JD (2001) Repeated exposure to inhaled toluene induces behavioral and neurochemical cross-sensitization to cocaine in rats. Psychopharmacology 154:198–204
Wiaderna D, Tomas T (2002) Assessment of long-term effects of exposure to toluene based on the analysis of selected behavioral responses with particular reference to the ability to trigger behavioral hypersensitivity in rats. Int J Occup Med Environ Health 15:239–245
Berenguer P, Soulage C, Perrin D, Pequignot JM, Abraini JH (2003) Behavioral and neurochemical effects induced by subchronic exposure to 40 ppm toluene in rats. Pharmacol Biochem Behav 74:997–1003
Benignus VA, Muller KE, Barton CN, Bittikofer JA (1981) Toluene levels in blood and brain of rats during and after respiratory exposure. Toxicol Appl Pharmacol 61(3):326–334
Greenberg MM (1997) The central nervous system and exposure to toluene: a risk characterization. Environ Res 72(1):1–7
Pryor GT, Rebert CS, Howd RA (1987) Hearing loss in rats caused by inhalation of mixed xylenes and styrene. J Appl Toxicol 7:55–61
Campagna D, Stengel B, Mergler D, Limasset JC, Diebold F, Michard D, Huel G (2001) Color vision and occupational toluene exposure. Neurotoxicol Teratol 23(5):473–480
Balster RL (1998) Neural basis of inhalant abuse. Drug Alcohol Depend 51:207–214
Mattia CJ, Adams JD, Bondy SC Jr (1993) Free radical induction in the brain and liver by products of toluene catabolism. Biochem Pharmacol 46(1):103–110
Zabedah MY, Razak M, Zakiak I, Zuraidah AB (2001) Profile of solvent abusers (glue sniffers) in East Malaysia. Malays J Pathol 23(2):105–109
Lam HR, Dalgaard M, Ladefoged O, Sørensen IK (2002) Development and vulnerability of rat brain and testes by parameters for apoptosis and ornithine decarboxylase activity. Comp Med 52:35–41
Hougaard KS, Hass U, Lund SP, Simonsen L (1999) Effects of prenatal exposure to toluene on postnatal development and behavior in rats. Neurotoxicol Teratol 21:241–250
Dalgaard M, Hossaini A, Hougaard KS, Hass U, Ladefoged O (2001) Developmental toxicity of toluene in male rats: effects on semen quality, testes morphology, and apoptotic neurodegeneration. Arch Toxicol 75:103–109
Hayashi A, Nagaoka M, Yamada K, Ichitani Y, Miake Y, Okado N (1998) Maternal stress induces synaptic loss and developmental disability of offspring. Int J Devl Neurosci 16:209–216
Lemaire V, Koehl M, Le Moal M, Abrous DN (2000) Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocamous. PNAS 97:11032–11037
Fujioka T, Sakata Y, Yamaguchi K, Shhibasaki T, Kato H, Nakamura S (1999) The effects of prenatal stress on the development of hypothalamic paraventricular neurons in fetal rats. Neuroscience 92:1079–1088
El-Tahir KE, Ashour MM, Al-Harbi MM (1993) The respiratory effects of the volatile oil of the black seed (Nigella sativa) in guinea-pigs: elucidation of the mechanism(s) of action. Gen Pharmacol 24:1115–1122
El-Kadi A, Kandil O (1987) The black seed (Nigella sativa) and immunity: its effect on human T cell subset. Fed Proc 46:1222
Hanafy MSM, Hatem ME (1991) Studies on the antimicrobial activity of Nigella sativa seed (black cumin). J Ethnopharmacol 34:275–278
Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M (2000) Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therap 55:379–382
Kanter M, Meral I, Yener Z, Ozbek H, Demir H (2003) Partial regeneration/proliferation of the ß-Cells in the islets of Langerhans by Nigella sativa L. in streptozocin-induced diabetic rats. Tohoku J Exp Med 20:213–219
Kanter M, Coskun O, Korkmaz A, Oter S (2004) Effects of Nigella sativa on oxidative stress and ß-Cell damage in streptozocin-induced diabetic rats. Anat Rec 279:685–691
Kanter M, Coskun O, Budancamanak M (2005) Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol 11(42):6684–6688
Kanter M, Demir H, Karakaya C, Ozbek H (2005) Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World J Gastroenterol 11(42):6662–6666
Kanter M, Coskun O, Uysal H (2006) The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol 80(4):217–224
Kanter M, Coskun O, Kalayci M, Buyukbas S, Cagavi F (2006) Neuroprotective effects of Nigella sativa on experimental spinal cord injury in rats. Hum Exp Toxicol 25(3):127–133
Mahfouz M, El-Dakhakhny M (1960) The isolation of a crystalline active principle from Nigella sativa L. seeds. J Pharm Sci UAR 1:1–19
Houghton PJ, Zarka R, Heras B, Hoult RS (1995) Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leucocytes and membrane lipid peroxidation. Planta Med 61:33–36
Badary OA, Nagi MN, Al-Shabanah OA, Al-Sawaf HA, Al-Sohaibani MO, Al-Bekairi AM (1997) Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can J Physiol Pharmacol 75:1356–1361
Al-Gharably M, Badary OA, Nagi MN et al (1997) Protective effect of thymoquinone against carbon tetrachloride-induced hepatotoxicity in mice. Res Commun Pharmacol Toxicol 2:41–50
Budancamanak M, Kanter M, Demirel A, Ocakci A, Uysal H, Karakaya C (2006) Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induced arthritis. Arch Toxicol 80(11):768–76
Fararh KM, Atoji Y, Shimizu Y, Takewaki T (2002) Isulinotropic properties of Nigella sativa oil in Streptozotocin plus Nicotinamide diabetic hamster. Res Vet Sci 73:279–282
Fararh KM, Shimizu Y, Shiina T, Nikami H, Ghanem MM, Takewaki T (2005) Thymoquinone reduces hepatic glucose production in diabetic hamsters. Res Vet Sci 79:219–223
Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580
Echeverria D, Fine L, Langolf G, Schork T, Sampaio C (1991) Acute behavioural comparisons of toluene and ethanol in human subjects. Br J Ind Med 48:750–761
Wang JD, Chen JD (1993) Acute and chronic neurological symptoms among paint workers exposed to mixtures of organic solvents. Environ Res 61:107–116
Kishi R, Harabuchi I, Katakura Y, Ikeda T, Miyake H (1993) Neurobehavioral effects of chronic occupational exposure to organic solvents among Japanese industrial painters. Environ Res 62:303–313
Deleu D, Hanssens Y (2000) Cerebellar dysfunction in chronic toluene abuse: beneficial response to amantadine hydrochloride. J Toxicol Clin Toxicol 38:37–41
Kamran S, Bakshi R (1998) MRI in chronic toluene abuse: low signal in the cerebral cortex on T2-weighted images. Neuroradiology 40:519–521
Yamanouchi N, Okada S, Kodama K, Hirai S, Sekine H, Murakami A, Komatsu N, Sakamoto T, Sato T (1995) White matter changes caused by chronic solvent abuse. Am J Neuroradiol 16:1643–1649
Saavedra H, Palestini M, De Marinis A (1996) Neuronal changes induced by chronic toluene exposure in the cat. Arch Ital Biol 134(3):217–225
Korbo L, Ladefoged O, Lam HR, Ostergaard G, West MJ, Arlien- Soborg P (1996) Neuronal loss in hippocampus in rats exposed to toluene. Neurotoxicology 17:359–366
Hu XJ, Ticku MK (1997) Functional characterization of a kindling-like model of ethanol withdrawal in cortical cultured neurons after chronic intermittent ethanol exposure. Brain Res 767:228–234
Bale AS, Tu Y, Carpenter-Hyland EP, Chandler LJ, Woodward JJ (2005) Alterations in glutamatergic and gabaergic ion channelactivity in hippocampal neurons following exposure to the abused inhalant toluene. Neuroscience 130:197–206
Altenkirch H, Mager J, Stoltenburg G, Helmbrecht J (1977) Toxic polyneuropathies after sniffing a glue thinner. J Neurol 214:137–52
Coskun O, Yuncu M, Kanter M, Buyukbas S (2006) Ebselen protects against oxidative and morphological effects of high concentration chronic toluene exposure on rat sciatic nerves. Eur J Gen Med 3(2):64–72
Baydas G, Reiter RJ, Nedzvetskii VS, Yasar A, Tuzcu M, Ozveren F, Canatan H (2003) Melatonin protects the central nervous system of rats against toluene-containing thinner intoxication by reducing reactive gliosis. Toxicol Lett 137(3):169–174
Aboutabl EA, El-Azzouny AA, Hammerschmidt FJ (1986) Aroma volatiles of Nigella sativa seeds. In: Brunke EJ (ed) Prog Essent Oil Res., Proceeding International Symposium Essential Oils. DeGruyer, Berlin, pp 49–55
Al-Shabanah OA, Badary OA, Nagi MN, Al-Gharably NM, Al-Rikabi AC, Al-Bekairi AM (1998) Thymoquinone protects against doxorubicin-induced cardiotoxicity without compromising its antitumor activity. J Exp Clin Cancer Res 17:193–198
El-Mahmoudy A, Matsuyama H, Borgan MA, Shimizu Y, El- Sayed MG, Minamoto N, Takewaki T (2002) Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages. Int Immunopharmacol 2:1603–1611
Al-Majed AA, Al-Omar FA, Nagi MN (2006) Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus. Eur J Pharmacol 543:40–47
Ladefoged O, Hougaard KS, Hass U, Sørensen IK, Lund SP (2004) Gitte Winkel Svendsen and Henrik Rye Lam, Effects of combined prenatal stress and toluene exposure on apoptotic neurodegeneration in cerebellum and hippocampus of rats. Basic Clin Pharmacol Toxicol 94:169–176
Wen X, Huang Y, Wang J (2006) Erythropoietin preconditioning on hippocampus neuronal apoptosis following status epilepticus induced by Li-pilocarpine in rats through anti-caspase-3 expression. Neurology India 54(1):58–63
Donald JM, Hooper K, Hopenhayn-Rich C (1991) Reproductive and developmental toxicity of toluene: a review. Environ Health Perspect 94:237–244
Ono A, Sekita K, Ogawa Y, Hirose A, Suzuki S, Saito M, Naito K, Kaneko T, Furuya T, Kawashima K, Yasuhara K, Matsumoto K, Tanaka S, Inoue T, Kurokawa Y (1996) Reproductive and developmental toxicity studies of toluene. II Effects of inhalation exposure on fertility in rats. J Environ Pathol Toxicol Oncol 15:9–20
Hass U, Lund SP, Hougaard KS, Simonsen L (1999) Developmental neurotoxicity after toluene inhalation exposure in rats. Neurotoxicol Teratol 21:349–357
Gelazonia L, Japaridze N, Svanidze I (2006) Pyramidal cell loss in hippocampus of young rats exposed to toluene. Georgian Med News 135:126–128
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kanter, M. Nigella sativa and Derived Thymoquinone Prevents Hippocampal Neurodegeneration After Chronic Toluene Exposure in Rats. Neurochem Res 33, 579–588 (2008). https://doi.org/10.1007/s11064-007-9481-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-007-9481-z