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Anti-Genotoxic and Anti-Cytotoxic Potential of Black Cumin Seed (Nigella sativa) Extract on Aluminum-exposed Human Lymphocyte Cells

Year 2018, Volume: 15 Issue: 3, 103 - 110, 12.12.2018

Abstract

Abstract

Background: The third most common
element in the world, aluminum (Al), causes genotoxicity, cytotoxicity, and oxidative
stress when its accumulation increases in the body. Conversely, Nigella sativa
seeds
(NSS) are a unique source of potent antioxidants, such as
thymoquinone (TQ) and
phenolic
compounds.
It is
currently unclear if NSS have protective potential against the toxic
efficiencies of Al.
Therefore, this
study aimed to assess the
anti-genotoxic
and anti-cytotoxic effects of the methanolic extract of Nigella sativa seeds (NSE) at different concentrations in human
peripheral blood lymphocyte cells (PBLC) against Al toxicity in in vitro conditions.

Methods: A comet
assay, micronucleus test, DNA fragmentation analyses, and
methyl-thiazol-tetrazolium (MTT) assay were used to evaluate the anti-genotoxic,
anti-cytotoxic, and anti-clastogenic effects of NSE
against the Al toxicity.

Results: The obtained
data showed that Al had genotoxic and cytotoxic effects at 100 μM of
concentration (p < 0.05) and that
NSE at low concentrations (0.1–2 μg/mL) had anti-genotoxic and anti-clastogenic
effects against Al-toxicity (p < 0.05).
It was also observed that NSE at or
above 2 μg/mL of concentration had genotoxic effects and that NSE at or above 5
μg/mL of concentration had cytotoxic effects (p < 0.05).









Conclusions: This study recommends
that the use of materials made of Al should be restricted and that NSS should
be consumed in low quantities to neutralize Al toxicity. 

References

  • Maya S, Prakash T, Madhu K Das, Goli D. Multifaceted effects of aluminium in neurodegenerative diseases: A review. Biomedicine and Pharmacotherapy. 2016;83:746‑54.
  • Celik H, Celik N, Kocyigit A, Dikilitas M. The relationship between plasma aluminum content, lymphocyte DNA damage, and oxidative status in persons using aluminum containers and utensils daily. Clinical Biochemistry. 2012;45(18):1629‑33.
  • Bhadauria M. Combined treatment of HEDTA and propolis prevents aluminum induced toxicity in rats. Food and Chemical Toxicology. 2012;50(7):2487‑95.
  • Paz LNF, Moura LM, Feio DCA, Cardoso M de SG, Ximenes WLO, Montenegro RC, et al. Evaluation of in vivo and in vitro toxicological and genotoxic potential of aluminum chloride. Chemosphere. 2017;175:130‑7.
  • Klotz K, Weistenhofer W, Neff F, Hartwig A, van Thriel C, Drexler H. The Health Effects of Aluminum Exposure. Deutsches Arzteblatt international. 2017;114(39):653‑9.
  • Abdel Moneim AE. Evaluating the potential role of pomegranate peel in aluminum-induced oxidative stress and histopathological alterations in brain of female rats. Biological Trace Element Research. 2012;150(1‑3):328‑36.
  • Shati AA, Elsaid FG, Hafez EE. Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup. Neuroscience. 2011;175:66‑74
  • Zhu Y, Han Y, Zhao H, Li J, Hu C, Li Y, et al. Suppressive effect of accumulated aluminum trichloride on the hepatic microsomal cytochrome P450 enzyme system in rats. Food and Chemical Toxicology. 2013;51(1):210‑4.
  • Kumar V, Gill KD. Aluminium neurotoxicity: neurobehavioural and oxidative aspects. Archives of Toxicology. 2009;83:965‑78.
  • Prakash A, Shur B, Kumar A. Naringin protects memory impairment and mitochondrial oxidative damage against aluminum-induced neurotoxicity in rats. International Journal of Neuroscience. 2013;123(9):636‑45.
  • Bouasla I, Bouasla A, Boumendjel A, Messarah M, Abdennour C, Boulakoud MS, et al. Nigella sativa Oil Reduces Aluminium Chloride-Induced Oxidative Injury in Liver and Erythrocytes of Rats. Biological Trace Element Research. 2014;162(1‑3):252‑61.
  • SanJuan-Reyes N, Gómez-Oliván LM, Galar-Martínez M, García-Medina S, Islas-Flores H, González-González ED, et al. NSAID-manufacturing plant effluent induces geno- and cytotoxicity in common carp (Cyprinus carpio). Science of The Total Environment. 2015;530‑531:1‑10.
  • Havakhah S, Sadeghnia HR, Hajzadeh M-A-R, Roshan NM, Shafiee S, Hosseinzadeh H, et al. Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage. Iranian journal of basic medical sciences. 2014;17(12):986‑92.
  • Farooqui Z, Ahmed F, Rizwan S, Shahid F, Khan AA, Khan F. Protective effect of Nigella sativa oil on cisplatin induced nephrotoxicity and oxidative damage in rat kidney. Biomedicine and Pharmacotherapy. 2017;85:7‑15.
  • Canayakin D, Bayir Y, Kilic Baygutalp N, Sezen Karaoglan E, Atmaca HT, Kocak Ozgeris FB, et al. Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa. Pharmaceutical biology. 2016;0209:1‑10.
  • Sarman H, Bayram R, Benek SB. Anticancer drugs with chemotherapeutic interactions with thymoquinone in osteosarcoma cells. European Review for Medical and Pharmacological Sciences. 2016;20(7):1263‑70.
  • Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pacific Journal of Tropical Biomedicine. 2013;3(5):337‑52.
  • Usta A, Dede S. The effect of thymoquinone on nuclear factor kappa B levels and oxidative DNA damage on experimental diabetic rats. Pharmacognosy Magazine. 2017;13(51):458.
  • Taha MME, Sheikh BY, Salim LZA, Mohan S, Khan A, Kamalidehghan B, et al. Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line. Cellular and Molecular Biology. 2016;62(6):97‑101.
  • Aycan IÖ, Tüfek A, Tokgöz O, Evliyaoǧlu O, Firat U, Kavak GÖ, et al. Thymoquinone treatment against acetaminophen-induced hepatotoxicity in rats. International Journal of Surgery. 2014;12(3):213‑8.
  • Seif AA. Nigella Sativa reverses osteoporosis in ovariectomized rats. BMC Complementary and Alternative Medicine. 2014;14(1):22.
  • Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death. Cellular and Molecular Neurobiology. 2010;30(4):591‑8.
  • Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental cell research. 1988;175(1):184‑91.
  • Kocyigit A, Koyuncu I, Taskin A, Dikilitas M, Bahadori F, Turkkan B. Antigenotoxic and antioxidant potentials of newly derivatized compound naringenin-oxime relative to naringenin on human mononuclear cells. Drug and Chemical Toxicology. 2016;39(1):66‑73.
  • Fenech M. The in vitro micronucleus technique. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2000;455(1‑2):81‑95.
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods. 1983;65(1‑2):55‑63.
  • Hashem MA, Mohamed WAM, Attia ESM. Assessment of protective potential of Nigella sativa oil against carbendazim- and/or mancozeb-induced hematotoxicity, hepatotoxicity, and genotoxicity. Environmental Science and Pollution Research. 2017;17:542-9.
  • Rastogi L, Feroz S, Pandey BN, Jagtap A, Mishra KP. Protection against radiation-induced oxidative damage by an ethanolic extract of Nigella sativa L. International journal of radiation biology. 2010;86:719‑31.
  • Zubair H, Khan HY, Sohail A, Azim S, Ullah MF, Ahmad A, et al. Redox cycling of endogenous copper by thymoquinone leads to ROS-mediated DNA breakage and consequent cell death: Putative anticancer mechanism of antioxidants. Cell Death and Disease. 2013;4(6):1-8.
  • Lima PDL, Leite DS, Vasconcellos MC, Cavalcanti BC, Santos R a, Costa-Lotufo L V, et al. Genotoxic effects of aluminum chloride in cultured human lymphocytes treated in different phases of cell cycle. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2013;45(7):1154‑9.
  • Zhang H, Shao D, Wu Y, Cai C, Hu C, Shou X, et al. Apoptotic responses of Carassius auratus lymphocytes to nodularin exposure in vitro. Fish and Shellfish Immunology. 2012;33(6):1229‑37.
  • Li M, Song M, Ren LM, Xiu CY, Liu JY, Zhu Y zhu, et al. AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway. Environmental Toxicology. 2016;31(4):385‑94.
  • Shahraki S, Khajavirad A, Shafei MN, Mahmoudi M, Tabasi NS. Effect of total hydroalcholic extract of Nigella sativa and its n-hexane and ethyl acetate fractions on ACHN and GP-293 cell lines. Journal of Traditional and Complementary Medicine. 2016;6(1):89‑96.
  • Palaniswamy D, Nithyanantham M, Raghu P, Dwarampudi L. Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa seeds. Pharmacognosy Magazine. 2012;8(32):268.
  • Saberzadeh J, Omrani M, Takhshid MA. Protective effects of nimodipine and lithium against aluminum-induced cell death and oxidative stress in PC12 cells. Iranian Journal of Basic Medical Sciences. 2016;19(11):1251‑7.
  • Djouina M, Esquerre N, Desreumaux P, Vignal C, Body-Malapel M. Toxicological consequences of experimental exposure to aluminum in human intestinal epithelial cells. Food and Chemical Toxicology. 2016;91:108‑16.

Alüminyum Toksisitesine Maruz Bırakılmış İnsan Lenfosit Hücrelerinde Çörek Otu (Nigella sativa) Ekstraktının Anti-Genotoksik ve Anti-Sitotoksik Etkileri

Year 2018, Volume: 15 Issue: 3, 103 - 110, 12.12.2018

Abstract

Özet



Amaç: Dünyadaki en yaygın üçüncü element olan alüminyum, vücutta
biriktiğinde genotoksisite, sitotoksisite ve oksidatif strese neden olmaktadır.
Ayrıca, çörek otunun timokinon ve fenolik bileşikler gibi
güçlü antioksidanların kaynağı olduğu da bilinen bir gerçektir.
Ancak çörek otunun, alüminyum toksisitesine karşı koruyucu etkiye
sahip olup olmadığı henüz araştırılmamıştır.
Bu nedenle, çalışmamızda
alüminyum toksisitesine karşı çörek otunun anti-genotoksik ve anti-sitotoksik
etkilerini in vitro hücre kültürü
ortamında araştırmayı amaçladık.



Materyal ve metod: İnsan lenfosit hücrelerinde,
alüminyum toksisitesine karşı, çörek otunun antisitotoksik ve antigenotoksik
etkileri, alkali tek hücre elektroforez yöntemi (comet assay), mikronükleus
test, metil tiyazol tetrazolium (MTT) test ve DNA fragmantasyon analizi ile
çalışıldı.



Bulgular: Elde edilen bulgular, alüminyumun 100 μM'da genotoksik ve sitotoksik etkili
olduğunu (p < 0,05)  ve düşük konsantrasyonlarda (0,1-2 μg / mL)
çörek otu ekstraktının alüminyum toksisitesine karşı anti-genotoksik ve
anti-klastojenik etkilere sahip olduğunu göstermektedir (p < 0,05).



Sonuç: Bu çalışma, alüminyumdan yapılmış malzemelerin kullanımının
kısıtlanması ve alüminyum toksisitesini nötralize etmek için düşük miktarlarda
çörek otunun tüketilmesi gerektiğini önermektedir.

References

  • Maya S, Prakash T, Madhu K Das, Goli D. Multifaceted effects of aluminium in neurodegenerative diseases: A review. Biomedicine and Pharmacotherapy. 2016;83:746‑54.
  • Celik H, Celik N, Kocyigit A, Dikilitas M. The relationship between plasma aluminum content, lymphocyte DNA damage, and oxidative status in persons using aluminum containers and utensils daily. Clinical Biochemistry. 2012;45(18):1629‑33.
  • Bhadauria M. Combined treatment of HEDTA and propolis prevents aluminum induced toxicity in rats. Food and Chemical Toxicology. 2012;50(7):2487‑95.
  • Paz LNF, Moura LM, Feio DCA, Cardoso M de SG, Ximenes WLO, Montenegro RC, et al. Evaluation of in vivo and in vitro toxicological and genotoxic potential of aluminum chloride. Chemosphere. 2017;175:130‑7.
  • Klotz K, Weistenhofer W, Neff F, Hartwig A, van Thriel C, Drexler H. The Health Effects of Aluminum Exposure. Deutsches Arzteblatt international. 2017;114(39):653‑9.
  • Abdel Moneim AE. Evaluating the potential role of pomegranate peel in aluminum-induced oxidative stress and histopathological alterations in brain of female rats. Biological Trace Element Research. 2012;150(1‑3):328‑36.
  • Shati AA, Elsaid FG, Hafez EE. Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup. Neuroscience. 2011;175:66‑74
  • Zhu Y, Han Y, Zhao H, Li J, Hu C, Li Y, et al. Suppressive effect of accumulated aluminum trichloride on the hepatic microsomal cytochrome P450 enzyme system in rats. Food and Chemical Toxicology. 2013;51(1):210‑4.
  • Kumar V, Gill KD. Aluminium neurotoxicity: neurobehavioural and oxidative aspects. Archives of Toxicology. 2009;83:965‑78.
  • Prakash A, Shur B, Kumar A. Naringin protects memory impairment and mitochondrial oxidative damage against aluminum-induced neurotoxicity in rats. International Journal of Neuroscience. 2013;123(9):636‑45.
  • Bouasla I, Bouasla A, Boumendjel A, Messarah M, Abdennour C, Boulakoud MS, et al. Nigella sativa Oil Reduces Aluminium Chloride-Induced Oxidative Injury in Liver and Erythrocytes of Rats. Biological Trace Element Research. 2014;162(1‑3):252‑61.
  • SanJuan-Reyes N, Gómez-Oliván LM, Galar-Martínez M, García-Medina S, Islas-Flores H, González-González ED, et al. NSAID-manufacturing plant effluent induces geno- and cytotoxicity in common carp (Cyprinus carpio). Science of The Total Environment. 2015;530‑531:1‑10.
  • Havakhah S, Sadeghnia HR, Hajzadeh M-A-R, Roshan NM, Shafiee S, Hosseinzadeh H, et al. Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage. Iranian journal of basic medical sciences. 2014;17(12):986‑92.
  • Farooqui Z, Ahmed F, Rizwan S, Shahid F, Khan AA, Khan F. Protective effect of Nigella sativa oil on cisplatin induced nephrotoxicity and oxidative damage in rat kidney. Biomedicine and Pharmacotherapy. 2017;85:7‑15.
  • Canayakin D, Bayir Y, Kilic Baygutalp N, Sezen Karaoglan E, Atmaca HT, Kocak Ozgeris FB, et al. Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa. Pharmaceutical biology. 2016;0209:1‑10.
  • Sarman H, Bayram R, Benek SB. Anticancer drugs with chemotherapeutic interactions with thymoquinone in osteosarcoma cells. European Review for Medical and Pharmacological Sciences. 2016;20(7):1263‑70.
  • Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pacific Journal of Tropical Biomedicine. 2013;3(5):337‑52.
  • Usta A, Dede S. The effect of thymoquinone on nuclear factor kappa B levels and oxidative DNA damage on experimental diabetic rats. Pharmacognosy Magazine. 2017;13(51):458.
  • Taha MME, Sheikh BY, Salim LZA, Mohan S, Khan A, Kamalidehghan B, et al. Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line. Cellular and Molecular Biology. 2016;62(6):97‑101.
  • Aycan IÖ, Tüfek A, Tokgöz O, Evliyaoǧlu O, Firat U, Kavak GÖ, et al. Thymoquinone treatment against acetaminophen-induced hepatotoxicity in rats. International Journal of Surgery. 2014;12(3):213‑8.
  • Seif AA. Nigella Sativa reverses osteoporosis in ovariectomized rats. BMC Complementary and Alternative Medicine. 2014;14(1):22.
  • Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death. Cellular and Molecular Neurobiology. 2010;30(4):591‑8.
  • Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental cell research. 1988;175(1):184‑91.
  • Kocyigit A, Koyuncu I, Taskin A, Dikilitas M, Bahadori F, Turkkan B. Antigenotoxic and antioxidant potentials of newly derivatized compound naringenin-oxime relative to naringenin on human mononuclear cells. Drug and Chemical Toxicology. 2016;39(1):66‑73.
  • Fenech M. The in vitro micronucleus technique. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2000;455(1‑2):81‑95.
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods. 1983;65(1‑2):55‑63.
  • Hashem MA, Mohamed WAM, Attia ESM. Assessment of protective potential of Nigella sativa oil against carbendazim- and/or mancozeb-induced hematotoxicity, hepatotoxicity, and genotoxicity. Environmental Science and Pollution Research. 2017;17:542-9.
  • Rastogi L, Feroz S, Pandey BN, Jagtap A, Mishra KP. Protection against radiation-induced oxidative damage by an ethanolic extract of Nigella sativa L. International journal of radiation biology. 2010;86:719‑31.
  • Zubair H, Khan HY, Sohail A, Azim S, Ullah MF, Ahmad A, et al. Redox cycling of endogenous copper by thymoquinone leads to ROS-mediated DNA breakage and consequent cell death: Putative anticancer mechanism of antioxidants. Cell Death and Disease. 2013;4(6):1-8.
  • Lima PDL, Leite DS, Vasconcellos MC, Cavalcanti BC, Santos R a, Costa-Lotufo L V, et al. Genotoxic effects of aluminum chloride in cultured human lymphocytes treated in different phases of cell cycle. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2013;45(7):1154‑9.
  • Zhang H, Shao D, Wu Y, Cai C, Hu C, Shou X, et al. Apoptotic responses of Carassius auratus lymphocytes to nodularin exposure in vitro. Fish and Shellfish Immunology. 2012;33(6):1229‑37.
  • Li M, Song M, Ren LM, Xiu CY, Liu JY, Zhu Y zhu, et al. AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway. Environmental Toxicology. 2016;31(4):385‑94.
  • Shahraki S, Khajavirad A, Shafei MN, Mahmoudi M, Tabasi NS. Effect of total hydroalcholic extract of Nigella sativa and its n-hexane and ethyl acetate fractions on ACHN and GP-293 cell lines. Journal of Traditional and Complementary Medicine. 2016;6(1):89‑96.
  • Palaniswamy D, Nithyanantham M, Raghu P, Dwarampudi L. Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa seeds. Pharmacognosy Magazine. 2012;8(32):268.
  • Saberzadeh J, Omrani M, Takhshid MA. Protective effects of nimodipine and lithium against aluminum-induced cell death and oxidative stress in PC12 cells. Iranian Journal of Basic Medical Sciences. 2016;19(11):1251‑7.
  • Djouina M, Esquerre N, Desreumaux P, Vignal C, Body-Malapel M. Toxicological consequences of experimental exposure to aluminum in human intestinal epithelial cells. Food and Chemical Toxicology. 2016;91:108‑16.
There are 36 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Hakim Çelik 0000-0002-7565-3394

Abdurrahim Koçyiğit 0000-0003-2335-412X

Cahit Bağcı This is me

İsmail Koyuncu 0000-0002-9469-4757

Ali Ziya Karakılçık This is me 0000-0002-6561-6346

Publication Date December 12, 2018
Submission Date October 9, 2018
Acceptance Date November 1, 2018
Published in Issue Year 2018 Volume: 15 Issue: 3

Cite

Vancouver Çelik H, Koçyiğit A, Bağcı C, Koyuncu İ, Karakılçık AZ. Alüminyum Toksisitesine Maruz Bırakılmış İnsan Lenfosit Hücrelerinde Çörek Otu (Nigella sativa) Ekstraktının Anti-Genotoksik ve Anti-Sitotoksik Etkileri. Harran Üniversitesi Tıp Fakültesi Dergisi. 2018;15(3):103-10.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty