anatomy Anatomy 1308-8459 Society of Anatomy and Clinical Anatomy Health Care Administration Sağlık Kurumları Yönetimi NIGELLA SATIVA PROTECTS AGAINST FORMALDEHYDE-INDUCED NEUROTOXICITY IN THE RAT FRONTAL CORTEX El-shahat Mohamad Abd El-rahman Mohamed Essa Tarek Ata Hesham Saad 02 01 2016 9 3 117 127 01 29 2016 Copyright © 2007, Anatomy 2007 Anatomy

Objectives: Nigella sativa (NS) is well known for its strong antioxidant properties. The aim of this study was to investigatethe potential protective effect of NS, as a potent antioxidant and free radical scavenger, on the rat frontal cortex followingformaldehyde (FA)-induced neuronal injury and oxidative stress.Methods: Forty albino rats were divided into four groups (n=10, each): control group received 1 ml distilled water, NS treatedgroup crushed seeds of NS at a single daily dose of 180 mg/kg/bw orally for two weeks, FA-treated group 10 mg/kg/bwFA i.p. daily for two weeks, and FA and NS treated group received 10 mg/kg/bw FA i.p. followed by a single dose of NS (180mg/kg/bw) orally for 2 weeks. The animals then were sacrificed and the frontal lobes were excised. Frontal cortex was stainedwith hematoxylen-eosin and caspase-3 immunohistochemistry to identify cell morphology and apoptosis. Lipid peroxide,nitric oxide, superoxide dismutase and glutathione levels were measured.Results: Histological examination revealed severe neurodegenerative changes in frontal cortex neurons in the FA-treated groupas observed with hematoxylen-eosin and caspase-3 immunohistochemistry. However, these changes were partly prevented inthe FA and NS-treated group. Apoptotic cell index in the frontal cortex decreased significantly in FA and NS treated rats comparedto FA-treated rats. In the FA-treated group, lipid peroxide levels increased, while nitric oxide and glutathione levelsdecreased significantly compared with controls. In the FA + NS treated group, nitric oxide, glutathione and superoxide dismutaselevels increased and lipid peroxide level decreased significantly when compared with the FA-treated group.Conclusion: NS administration protects frontal cortex neurons against oxidative damage induced by FA.

 cerebral cortex formaldehyde neuronal injury Nigella sativa oxidative stress rat Cheng G, Shi Y, Sturla SJ, Jalas JR, McIntee EJ, Villalta PW, Wang M, Hecht SS. Reactions of formaldehyde plus acetaldehyde with deoxyguanosine and DNA: formation of cyclic deoxyguanosine adducts and formaldehyde cross-links. Chem Res Toxicol ;16:145–52. Metz B, Kersten GF, Hoogerhout P, Brugghe HF, Timmermans HA, de Jong A, Meiring H, ten Hove J, Hennink WE, Crommelin DJ, Jiskoot W. Identification of formaldehyde-induced modifications in proteins: reactions with model peptides. J Biol Chem ;279:6235–43. Chohen BL, Pangnillo MK, Musikant BL, Deutsch AS. Formaldehyde evaluation from endoplasmic materials. Oral Health 1998; 88:37–9. Sarnak MJ, Long J, King AJ. Intravascular formaldehyde instillation and renal complication. Clin Nephrol 1999;51:122–5. Conaway CC, Whysner J, Verna LK, Williams GM. Formaldehyde mechanistic data and risk assessement: endogenous protection from DNA adduct formation. Pharmacol Ther 1996;71:29–55. Trezl L, Hullan L, Szavas T, Csiba A, Szende B. Determination of endogenous formaldehyde in plants (fruits) bound to L-arginine and its relation to the folate cycle, photosynthesis and apoptosis. Acta Biol Hung 1998;49:253–63. Feron, VJ, Till HP, de Vrijer F, Woutersen RA, Cassee FR, van Bladeren PJ. Aldehyde: occurrence, carcinogenic potential, mechanism of action and risk assessment. Mutal Res 1991;259:363–85. Simith AE. Formaldehyde. Occup Med 1992;42:83–8. Ozen OA, Songur A, Sarsilmaz M, Yaman M, Kus I. Zinc, copper and iron concentrations in cerebral cortex of male rats exposed to formaldehyde inhalation. J Trace Elem Med Biol 2003;17:207–9. Songur A, Akpolat N, Kus I, Ozen OA, Zararsiz I, Sarsilmaz M. The effects of the inhaled formaldehyde during the early postnatal period in the hippocampus of rats: a morphological and immunohistochemical study. Neurosci Res Commun 2003;33:168–78. Trezl L, Tyihak E, Lotlikar PD. Non-enzymatic protein methylation and its biological significance in protein methylation. In: Paik WK, Kim S, editors. Protein methylation. Boca Raton (FL): CRC Press; 1990. Solomons K and Cochrane JW. Formaldehyde toxicity. Part II. Review of acute and chronic effects on health. S Afr Med J 1984; :103–6. Kilburn KH. Neurobehavioural impairment and seizures from formaldehyde. Arch Environ Health 1994;49:37–44. Sorg BA, Hochstatter T. Behavioral sensitization after repeated formaldehyde exposure in rats. Toxicol Ind Health 1999;15:346–55. Pitten FA, Kramer A, Herrmann K, Bremer J, Koch S. Formaldehyde neurotoxicity in animal experiments. Pathol Res Pract 2000;196:193–8. Lu Z, Li CM, Qiao Y, Yan Y, Yang X. Effect of inhaled formaldehyde on learning and memory of mice. Indoor Air 2008;18:77–83. Stroup NE, Blair A, Erickson GE. Brain cancer and other causes of deaths in anatomists. J Natl Cancer Inst 1986;77:1217–24. Reiter RL. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 1995;9:526–33. Patil AJ, Bhagwat VR, Patil JA, Dongre NN, Ambekar JG, Jailkhani R, Das KK. Effect of formaldehyde exposure on the activity of superoxide dismutase and catalase in battery manufacturing workers (BMW) of western Maharashtra (India) with reference to heme biosynthesis. Int J Environ Res Public Health ;3:329–37. Halliwell B. Antioxidant and human disease: a general introduction. Nutrition 1997;55:544–52. Kadiiska MB, Mason RP. Acute methanol intoxication generates free radicals in rats: an ESR spin trapping investigation. Free Radic Boil Med 2000;28:1106–14. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. Oxford: Clarendon Press; 1989;186–87. El-Tahir KE, Ashour MM, Al-Harbi MM. 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 1993; :1115–22. Ghosheh OA, Houdi AA, Crooks PA. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J Pharm Biomed Anal 1999;19:757–62. Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine 2007;14:621–7. Padhye S, Banerjee S, Ahmad A, Mohammad R, Sarkar FH. From here to eternity-the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond. Cancer Ther 2008;6:495–510. Hanafy MSM, Hatem ME. Studies on the antimicrobial activity of Nigella sativa seed (black cumin). J Ethnopharmacol 1991;34:275–78. Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M. Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rats. Therapie 2000;55:379–82. Kanter M, Coskun O, Budancamanak M. Hepato-protective effects of Nigella sativa L and Urtica diodica L on the lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol 2005;11:6684–8. Kanter M, Coskun O, Uysal H. The antioxidative and antihistaminic effects of Nigella sativa and its major constituents, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol ;80:217–24. El-Kadi A, Kandil O. The black seed (Nigella sativa) and immunity: its effect on human T cell. Subset Fed Proc 1987;46:1222. Uçmakl› E,Armutcu F, Öztürk A. The effects of formaldehyde intoxication on the inducible nitric oxide synthase expression and nitric oxide level in the liver tissue of rats. Turk J Med Sci 2013;43:52–6. Kanter M. Protective effects of Nigella sativa on formaldehydeinduced neuronal injury in frontal cortex. T›p Araflt›rmalar› Dergisi ;8:1–8. Wang T, Zhao L, Guo Y, Zhang M, Pei H. Picroside II Inhibits neuronal apoptosis and improves the morphology and structure of brain tissue following cerebral ischemic injury in rats. PLoS ONE ;10:e0124099. Thayer WS. Serum lipid peroxides in rats treated chronically with adriamycin. Biochem Pharmacol 1984;33:2259–63. Van Bezooijen RL, Que I, Ederveen AG, Kloosterboer HJ, Papapoulos SE, Lowik CW. Plasma nitrate+nitrite levels are regulated by ovarian steroids but do not correlate with trabecular bone mineral density in rats. J Endocrinol 1998;159:27–34. Misra HP, Fridouich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 274:3170–75. Dutta P, Seirafi J, Halpin D, Pinto J, Rivlin R. Acute ethanol exposure alters hepatic glutathione metabolism in riboflavin deficiency. Alcohol 1995;12:43–7. Salonen H, Pasanen AL, Lappalainen S. Volatile organic compounds and formaldehyde as explaining factors for sensory irritation in office enviroments. J Occup Environ Hyg 2009;6:239–47. Zhang Y, Liu X, McHale C, Li R, Zhang L. Bone marrow injury induced via oxidative stress in mice by inhalation exposure to formaldehyde. PLoS ONE 2013;8:e74974. Usanmaz SE, Akarsu ES, Vural N. Neurotoxic effect of acute and sub-acute formaldehyde exposures in mice. Environ Toxicol Pharmacol 2002;11:93–100. Datta NJ, Namasivayam A. In vitro effect of methanol on folatedeficient rat hepatocyte. Drug Alcohol Depend 2003;71:87–91. Farooqui MY, Upreti RK, Ahmed AE, Ansari GA. Influence of intraperitoneally administered formaldehyde on bile production and tissue glutathione levels in rats. Res Commun Chem Pathol Pharmacol 1986;53:233–6. Tang XQ, Zhuang YY, Zhang P, Fang HR, Zhou CF, Gu HF, Zhang H, Wang CY. Formaldehyde impairs learning and memory involving the disturbance of hydrogen sulfide generation in the hippocampus of rats. J Mol Neurosci 2013;49:140–9. Daniel S, Limson JL, Amichand D, Watkins GM, Daya S. Through metal binding, curcumin protects against lead and cadmium- induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Inorg Biochem ;98:266–75. Bennet C, Bettaiya R, Rajanna S, Baker L, Yallapragada PR, Brice JJ, White SL, Bokara KK. Region specific increase in the antioxidant enzymes and lipid peroxidation products in the brain of rats exposed to lead. Free Radic Res 2007;41:267–73. Peluffo G, Calcerrada P, Piacenza L, Pizzano N, Radi R. Superoxide-mediated inactivation of nitric oxide and peroxynitrite formation by tobacco smoke in vascular endothelium: studies in cultured cells and smokers. Am J Physiol 2009;296:1781–92. Kurata M, Suzuki M, Agar NS. Antioxidant systems and erythrocyte life-span in mammals. Comp Biochem Physiol B 1993;106:477–87. Zararsiz I, Sonmez MF. Effects of omega-3 essential fatty acids against formaldehyde induced nephropathy in rats. Toxicol Ind Health 2006; 22:223–9. Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 1995;18:321–36. Ding Y, Gonick HC, Vaziri ND. Lead promotes hydroxyl radical generation and lipid peroxidation in cultured aortic endothelial cells. Am J Hypertens 2000;13:552–55. Saxena G, Flora SJS. Lead induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiolchelator in rats. J Biochem Mol Toxicol 2004;18:221–33. Badary OA, Taha RA, Gamal A, El-Din M, Abdel-Wahab MH. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 2003; 26:87–98. Nagi MN, Alam K, Badary OA, Al-Shabanah OA, Al- Sawaf HA, Al-Bekairi AM. Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int 1999;47:153–9. Kruk I, Michalska T, Lichszteld K, Kladna A, Aboul- Enein HY. The effect of thymol and its derivatives on reactions reactive oxygen species. Chemosphere 2000; 41:1059–64. Al-Omar FA, Nagi MN, Abdulgadir MM, Al-Joni KS, Al-Majed AA. Immediate and delayed treatments with curcumin prevent forebrain ischemia-induced neuronal damage and oxidative Ismail M, Al-Naqeep G, Chan KW. Nigella sativa thymoquinonerich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemicrats. Free Radic Biol Med 2010;48:664–72. Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indexes of lipid-peroxidation and peroxidative tissueinjury free radical biology and medicine. Free Radic Biol Med ;9:515–40. Sheikh BY, Mohamadin AM. Thymoquinone a potential therapy for cerebral oxidative stress. Asian J Nat Appl Sci 2012;1:76–92. Nagi MN, Mansour MA. Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 2000;41:283–89.