Skip to content
2000
Volume 6, Issue 1
  • ISSN: 2665-9786
  • E-ISSN: 2665-9794

Abstract

Background

Neem, known for its medicinal benefits, such as anti-inflammatory, antioxidant, and anti-cancer properties, can serve as a complementary or alternative treatment. Research has also indicated that neem extracts lessen the harmful effects of the chemotherapy drug cisplatin on healthy cells while still preserving its ability to target cancer cells effectively. Different parts of the Neem tree, such as leaves, bark, fruit, flowers, oil, and gum, have been traditionally used in herbal medicine for treating various health conditions, including cancer, hypertension, heart disease, and diabetes.

Objective

The effect of neem extract was studied on the Ethyl methanesulphonate (EMS) (an anti-cancerous drug)-induced toxicity in the third instar larvae of transgenic () .

Methods

The third instar larvae were exposed to 25 µM of EMS alone and along with 4×10-3 g/ml, 8×10-3 g/ml, 12×10-3 g/ml, and 16×10-3 g/ml of neem extract (NE) mixed in diet for 24 hrs.

Results

A significant increase in toxicity was observed in the larvae exposed to 25 µM of EMS. A dose-dependent significant decrease in the toxic effects was observed in the larvae exposed to various doses of neem extract. The GCMS analysis of the neem extract showed the presence of Phytol and α-tocopherol as major compounds.

Conclusion

The reduction in the toxicity induced by EMS is mainly attributed to phytol and α-tocopherol.

Loading

Article metrics loading...

/content/journals/cnt/10.2174/0126659786331452241101053153
2024-12-03
2025-09-29
Loading full text...

Full text loading...

References

  1. IslasJ.F. AcostaE. G-BuentelloZ. Delgado-GallegosJ.L. Moreno-TreviñoM.G. EscalanteB. Moreno-CuevasJ.E. An overview of Neem (Azadirachta indica) and its potential impact on health.J. Funct. Foods20207410417110.1016/j.jff.2020.104171
    [Google Scholar]
  2. DashS.P. DixitS. SahooS. Phytochemical and biochemical characterizations from leaf extracts from Azadirachta Indica: An important medicinal plant.Biochem. Anal. Biochem.2017632321611009
    [Google Scholar]
  3. ChattopadhyayR.R. Possible mechanism of antihyperglycemic effect of Azadirachta indica leaf extract: Part V.J. Ethnopharmacol.199967337337610.1016/S0378‑8741(99)00094‑X10617075
    [Google Scholar]
  4. SalehzadehA. AkhkhaA. CushleyW. AdamsR.L.P. KuselJ.R. StrangR.H.C. The antimitotic effect of the neem terpenoid azadirachtin on cultured insect cells.Insect Biochem. Mol. Biol.200333768168910.1016/S0965‑1748(03)00057‑212826095
    [Google Scholar]
  5. NarkhedeA.N. JagtapS.D. KasoteD.M. KulkarniO.P. HarsulkarA.M. Comparative immunomodulation potential of Tinospora cordifolia (Willd.) Miers ex Hook. F., Tinospora sinensis (Lour.) Merrill and Tinospora cordifolia growing on Azadirachta indica A. Juss.Indian J. Exp. Biol.2014528808813
    [Google Scholar]
  6. HwangS.J. KimY.W. ParkY. LeeH.J. KimK.W. Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells.Inflamm. Res.2014631819010.1007/s00011‑013‑0674‑424127072
    [Google Scholar]
  7. SchumacherM. CerellaC. ReuterS. DicatoM. DiederichM. Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway.Genes Nutr.20116214916010.1007/s12263‑010‑0194‑621484152
    [Google Scholar]
  8. NitureN.T. AnsariA.A. NaikS.R. Anti-hyperglycemic activity of rutin in streptozotocin-induced diabetic rats: an effect mediated through cytokines, antioxidants and lipid biomarkers.Indian J. Exp. Biol.201452772072725059040
    [Google Scholar]
  9. BharatP. SagarR. SulavR. AnkitP. Investigations of antioxidant and antibacterial activity of leaf extracts of Azadirachta indica.Afr. J. Biotechnol.201514463159316310.5897/AJB2015.14811
    [Google Scholar]
  10. BrahmachariG. Neem--an omnipotent plant: a retrospection.ChemBioChem20045440842110.1002/cbic.20030074915185362
    [Google Scholar]
  11. PaulR. PrasadM. SahN.K. Anticancer biology of Azadirachta indica L (neem): A mini review.Cancer Biol. Ther.201112646747610.4161/cbt.12.6.1685021743298
    [Google Scholar]
  12. YadavD.K. BharitkarY.P. ChatterjeeK. GhoshM. MondalN.B. SwarnakaS. Importance of Neem Leaf: An insight into its role in combating diseases.Indian J. Exp. Biol.2016541170871830179391
    [Google Scholar]
  13. GockeE. BürginH. MüllerL. PfisterT. Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate.Toxicol. Lett.2009190325426510.1016/j.toxlet.2009.03.01619857796
    [Google Scholar]
  14. MukhopadhyayI. ChowdhuriD.K. BajpayeeM. DhawanA. Evaluation of in vivo genotoxicity of cypermethrin in Drosophila melanogaster using the alkaline Comet assay.Mutagenesis2004192859010.1093/mutage/geh00714981154
    [Google Scholar]
  15. FestingM.F.W. BaumansV. CombesR.D. HaiderM. HendriksenC.F.M. HowardB.R. LovellD.P. MooreG.J. OverendP. WilsonM.S. Reducing the use of laboratory animals in biomedical research: problems and possible solutions.Altern. Lab. Anim.199826328330110.1177/02611929980260030526042346
    [Google Scholar]
  16. BenfordD.J. HanleyA.B. BottrillK. OehlschlagerS. BallsM. BrancaF. CastegnaroJ.J. DescotesJ. HemminikiK. LindsayD. SchilterB. Biomarkers as Predictive Tools in Toxicity Testing.Altern. Lab. Anim.200028111913110.1177/026119290002800104
    [Google Scholar]
  17. RandM.D. DaoJ.C. ClasonT.A. Methylmercury disruption of embryonic neural development in Drosophila.Neurotoxicology200930579480210.1016/j.neuro.2009.04.00619409416
    [Google Scholar]
  18. HirschH.V.B. MercerJ. SambaziotisH. HuberM. StarkD.T. Torno-MorleyT. HollocherK. GhiradellaH. RudenD.M. Behavioral effects of chronic exposure to low levels of lead in Drosophila melanogaster.Neurotoxicology200324343544210.1016/S0161‑813X(03)00021‑412782108
    [Google Scholar]
  19. Muñiz OrtizJ.G. OpokaR. KaneD. CartwrightI.L. Investigating arsenic susceptibility from a genetic perspective in Drosophila reveals a key role for glutathione synthetase.Toxicol. Sci.2009107241642610.1093/toxsci/kfn19218779381
    [Google Scholar]
  20. BonillaE. ContrerasR. Medina-LeendertzS. MoraM. VillalobosV. BravoY. Minocycline increases the life span and motor activity and decreases lipid peroxidation in manganese treated Drosophila melanogaster.Toxicology20122941505310.1016/j.tox.2012.01.01622330257
    [Google Scholar]
  21. RanganathanS. DavisD.G. HoodR.D. Developmental toxicity of ethanol in Drosophila melanogaster.Teratology1987361454910.1002/tera.14203601073118495
    [Google Scholar]
  22. PosgaiR. Cipolla-McCullochC.B. MurphyK.R. HussainS.M. RoweJ.J. NielsenM.G. Differential toxicity of silver and titanium dioxide nanoparticles on Drosophila melanogaster development, reproductive effort, and viability: Size, coatings and antioxidants matter.Chemosphere2011851344210.1016/j.chemosphere.2011.06.04021733543
    [Google Scholar]
  23. GuptaS. KnowltonA.A. HSP60, Bax, apoptosis and the heart.J. Cell. Mol. Med.200591515810.1111/j.1582‑4934.2005.tb00336.x15784164
    [Google Scholar]
  24. SiddiqueY.H. AkhtarS. Rahul AnsariM.S. ShakyaB. JyotiS. NazF. Protective effect of Luteolin against methyl methanesulfonate-induced toxicity.Toxin Rev.2021401657610.1080/15569543.2018.1564142
    [Google Scholar]
  25. Ali KhanM. JyotiS. Rahul NazF. AraG. AfzalM. SiddiqueY.H. Effect of lemon grass extract against methyl methanesulfonate-induced toxicity.Toxin Rev.20214041172118610.1080/15569543.2019.1657152
    [Google Scholar]
  26. FatimaA. KhanamS. RahulR. JyotiS. NazF. AliF. SiddiqueY.H. Protective effect of tangeritin in transgenic Drosophila model of Parkinson’s disease.Front. Biosci. (Elite Ed.)201791445327814588
    [Google Scholar]
  27. KhanamS. FatimaA. JyotiR.S. AliF. NazF. ShakyaB. SiddiqueY.H. Protective effect of capsaicin against methyl methanesulphonate induced toxicity in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9.Chin. J. Nat. Med.201715427128010.1016/S1875‑5364(17)30044‑428527512
    [Google Scholar]
  28. SiddiqueY.H. AraG. AfzalM. Effect of ethinylestradiol on hsp70 expression in transgenic Drosophila melanogaster (hsp70-lacZ) Bg9.Pharmacologyonline20111398405
    [Google Scholar]
  29. SiddiqueY.H. AraG. AfzalM. Effect of the steroid K-canrenoate on hsp70 expression and tissue damage in transgenic Drosophila melanogaster (hsp70-lacZ) Bg9.J. Insect Sci.20121219223427921
    [Google Scholar]
  30. MisraJ.R. HornerM.A. LamG. ThummelC.S. Transcriptional regulation of xenobiotic detoxification in Drosophila.Genes Dev.201125171796180610.1101/gad.1728091121896655
    [Google Scholar]
  31. GloverJ.R. TkachJ.M. Crowbars and ratchets: Hsp100 chaperones as tools in reversing protein aggregation.Biochem. Cell Biol.200179555756810.1139/o01‑14811716297
    [Google Scholar]
  32. HouryW. Chaperone-assisted protein folding in the cell cytoplasm.Curr. Protein Pept. Sci.20012322724410.2174/138920301338113412369934
    [Google Scholar]
  33. PrattW.B. ToftD.O. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery.Exp. Biol. Med. (Maywood)2003228211113310.1177/15353702032280020112563018
    [Google Scholar]
  34. NazirA. MukhopadhyayI. SaxenaD.K. ChowdhuriD.K. Chlorpyrifos-induced hsp70 expression and effect on reproductive performance in transgenic Drosophila melanogaster (hsp70-lacZ) Bg9.Arch. Environ. Contam. Toxicol.200141444344910.1007/s00244001027011598781
    [Google Scholar]
  35. NazirA. MukhopadhyayI. SaxenaD.K. SiddiquiM.S. ChowdhuriD.K. Evaluation of toxic potential of captan: Induction of hsp70 and tissue damage in transgenic drosophila melanogaster (hsp70‐lacZ) Bg 9 .J. Biochem. Mol. Toxicol.20031729810710.1002/jbt.1006612717743
    [Google Scholar]
  36. LisJ.T. SimonJ.A. SuttonC.A. New heat shock puffs and β=galactosidase activity resulting from transformation of Drosophila with an hsp70-lacZ hybrid gene.Cell198335240341010.1016/0092‑8674(83)90173‑36418386
    [Google Scholar]
  37. Kar ChowdhuriD. SaxenaD.K. ViswanathanP.N. Effect of Hexachlorocyclohexane (HCH), Its Isomers, and Metabolites on Hsp70 Expression in TransgenicDrosophila melanogaster.Pestic. Biochem. Physiol.1999631152510.1006/pest.1998.2390
    [Google Scholar]
  38. JollowD.J. MitchellJ.R. ZampaglioneN. GilletteJ.R. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite.Pharmacology197411315116910.1159/0001364854831804
    [Google Scholar]
  39. HabigW.H. PabstM.J. FleischnerG. GatmaitanZ. AriasI.M. JakobyW.B. The identity of glutathione S-transferase B with ligandin, a major binding protein of liver.Proc. Natl. Acad. Sci. USA197471103879388210.1073/pnas.71.10.38794139704
    [Google Scholar]
  40. OhkawaH. OhishiN. YagiK. Reaction of linoleic acid hydroperoxide with thiobarbituric acid.J. Lipid Res.19781981053105710.1016/S0022‑2275(20)40690‑X103988
    [Google Scholar]
  41. HawkinsC.L. MorganP.E. DaviesM.J. Quantification of protein modification by oxidants.Free Radic. Biol. Med.200946896598810.1016/j.freeradbiomed.2009.01.00719439229
    [Google Scholar]
  42. KaterjiM. Duerksen-HughesP.J. DNA damage in cancer development: special implications in viral oncogenesis.Am. J. Cancer Res.20211183956397934522461
    [Google Scholar]
  43. ParryJ.M. Comparison of the effects of ultraviolet light and ethylmethanesulphonate upon the frequency of mitotic recombination in yeast.Mol. Gen. Genet.19691061667210.1007/BF003328215370118
    [Google Scholar]
  44. MorranL.T. OhderaA.H. PhillipsP.C. Purging deleterious mutations under self fertilization: paradoxical recovery in fitness with increasing mutation rate in Caenorhabditis elegans.PLoS One2010512e1447310.1371/journal.pone.001447321217820
    [Google Scholar]
  45. HeadR.J. FayM.F. CosgroveL. Y C FungK. Rundle-ThieleD. MartinJ.H. Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.Cancer Biol. Ther.2017181291792610.1080/15384047.2017.138568029020502
    [Google Scholar]
  46. OwagboriayeF.O. DedekeG.A. AshidiJ.S. AladesidaA.A. OlootoW.E. Effect of gasoline fumes on reproductive function in male albino rats.Environ. Sci. Pollut. Res. Int.20182554309431910.1007/s11356‑017‑0786‑429181751
    [Google Scholar]
  47. DanishM. FatimaA. KhanamS. JyotiS. Rahul AliF. NazF. SiddiqueY.H. Evaluation of the toxic potential of calcium carbide in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9.Chemosphere201513946947810.1016/j.chemosphere.2015.07.07726298668
    [Google Scholar]
  48. Mukhtar-Un-Nisar AndrabiS. TamannaS. Rahul NazF. SiddiqueY.H. Toxic potential of sodium hypochlorite in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ) Bg 9 .Toxin Rev.202241389190310.1080/15569543.2021.1955711
    [Google Scholar]
  49. GuvenK. PowerR.S. AvramidesS. AllenderR. de PomeraiD.I. The toxicity of dithiocarbamate fungicides to soil nematodes, assessed using a stress-inducible transgenic strain ofCaenorhabditis elegans.J. Biochem. Mol. Toxicol.199913632433310.1002/(SICI)1099‑0461(1999)13:6<324::AID‑JBT6>3.0.CO;2‑Q10487420
    [Google Scholar]
  50. StringhamE.G. CandidoE.P.M. Transgenic hsp 16‐Lacz strains of the soil nematode caenorhabditis elegans as biological monitors of environmental stress.Environmental Toxicology and Chemistry: An International Journal199413812111220
    [Google Scholar]
  51. GaryR.K. KindellS.M. Quantitative assay of senescence-associated β-galactosidase activity in mammalian cell extracts.Anal. Biochem.2005343232933410.1016/j.ab.2005.06.00316004951
    [Google Scholar]
  52. FormanH.J. ZhangH. RinnaA. Glutathione: Overview of its protective roles, measurement, and biosynthesis.Mol. Aspects Med.2009301-211210.1016/j.mam.2008.08.00618796312
    [Google Scholar]
  53. KumarS. TrivediP.K. Glutathione S-Transferases: Role in Combating Abiotic Stresses Including Arsenic Detoxification in Plants.Front. Plant Sci.2018975110.3389/fpls.2018.0075129930563
    [Google Scholar]
  54. CheungT. NigamP. Owusu-ApentenR. Antioxidant activity of curcumin and neem (Azadirachta indica) powders: Combination studies with ALA using MCF-7 breast cancer cells.J. Appli. Life Scie. Int.20164311210.9734/JALSI/2016/22273
    [Google Scholar]
  55. PandeyG. VermaK.K. SinghM. Evaluation of phytochemical, antibacterial and free radical scavenging properties of Azadirachta indica (neem) leaves.Int. J. Pharm. Pharm. Sci.201462444447
    [Google Scholar]
  56. ChunH.S. GibsonG.E. DeGiorgioL.A. ZhangH. KiddV.J. SonJ.H. Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism.J. Neurochem.20017641010102110.1046/j.1471‑4159.2001.00096.x11181820
    [Google Scholar]
  57. Tada-OikawaS. HirakuY. KawanishiM. KawanishiS. Mechanism for generation of hydrogen peroxide and change of mitochondrial membrane potential during rotenone-induced apoptosis.Life Sci.200373253277328810.1016/j.lfs.2003.06.01314561532
    [Google Scholar]
  58. CarvourM. SongC. KaulS. AnantharamV. KanthasamyA. KanthasamyA. Chronic low-dose oxidative stress induces caspase-3-dependent PKCdelta proteolytic activation and apoptosis in a cell culture model of dopaminergic neurodegeneration.Ann. N. Y. Acad. Sci.20081139119720510.1196/annals.1432.02018991865
    [Google Scholar]
  59. SleeE.A. HarteM.T. KluckR.M. WolfB.B. CasianoC.A. NewmeyerD.D. WangH.G. ReedJ.C. NicholsonD.W. AlnemriE.S. GreenD.R. MartinS.J. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner.J. Cell Biol.1999144228129210.1083/jcb.144.2.2819922454
    [Google Scholar]
  60. ZuoY. XiangB. YangJ. SunX. WangY. CangH. YiJ. Oxidative modification of caspase-9 facilitates its activation via disulfide-mediated interaction with Apaf-1.Cell Res.200919444945710.1038/cr.2009.1919238172
    [Google Scholar]
  61. Munné-BoschS. The role of -tocopherol in plant stress tolerance.J. Plant Physiol.2005162774374810.1016/j.jplph.2005.04.02216008098
    [Google Scholar]
  62. WijtmansM. PrattD.A. ValgimigliL. DiLabioG.A. PedulliG.F. PorterN.A. 6-Amino-3-pyridinols: towards diffusion-controlled chain-breaking antioxidants.Angew. Chem. Int. Ed.200342364370437310.1002/anie.20035188114502714
    [Google Scholar]
  63. NaganoM. BataliniC. Phytochemical screening, antioxidant activity and potential toxicity of Azadirachta indica A. Juss (neem) leaves.Colombian J. Chem. Pharmaceut. Sci.20215012947
    [Google Scholar]
  64. AgrawalS. Bablani PopliD. SircarK. ChowdhryA. A review of the anticancer activity of Azadirachta indica (Neem) in oral cancer.J. Oral Biol. Craniofac. Res.2020b10220620910.1016/j.jobcr.2020.04.00732489822
    [Google Scholar]
  65. BiswasK. Biological activities and medicinal properties of neem (Azadirachta indica).Curr. Sci.2002821113361345
    [Google Scholar]
  66. AlabiO.A. AnokwuruC.P. EzekielC.N. AjibayeO. NwadikeU.J. FasasiO. AbuM. Anti-mutagenic and Anti-genotoxic Effect of Ethanolic Extract of Neem on Dietary-aflatoxin Induced Genotoxicity in Mice.J. Biol. Sci. (Faisalabad, Pak.)201111430731310.3923/jbs.2011.307.313
    [Google Scholar]
  67. GovindachariT.R. Chemical and biological investigations on Azadirachta indica (the neem tree).Curr. Sci.1992633117122
    [Google Scholar]
  68. SchaafO. JarvisA.P. van der EschS.A. GiagnacovoG. OldhamN.J. Rapid and sensitive analysis of azadirachtin and related triterpenoids from Neem (Azadirachta indica) by high-performance liquid chromatography–atmospheric pressure chemical ionization mass spectrometry.J. Chromatogr. A20008861-2899710.1016/S0021‑9673(00)00492‑110950279
    [Google Scholar]
  69. UpadhyayS.N. DhawanS. GargS. TalwarG.P. Immunomodulatory effects of neem (Azadirachta indica) oil.Int. J. Immunopharmacol.19921471187119310.1016/0192‑0561(92)90054‑O1452404
    [Google Scholar]
  70. IslamM.T. AliE.S. UddinS.J. ShawS. IslamM.A. AhmedM.I. Chandra ShillM. KarmakarU.K. YarlaN.S. KhanI.N. BillahM.M. PieczynskaM.D. ZenginG. MalainerC. NicolettiF. GuleiD. Berindan-NeagoeI. ApostolovA. BanachM. YeungA.W.K. El-DemerdashA. XiaoJ. DeyP. YeleS. JóźwikA. StrzałkowskaN. MarchewkaJ. RengasamyK.R.R. HorbańczukJ. KamalM.A. MubarakM.S. MishraS.K. ShilpiJ.A. AtanasovA.G. Phytol: A review of biomedical activities.Food Chem. Toxicol.2018121829410.1016/j.fct.2018.08.03230130593
    [Google Scholar]
  71. GuimarãesA.G. OliveiraG.F. MeloM.S. CavalcantiS.C.H. AntoniolliA.R. BonjardimL.R. SilvaF.A. SantosJ.P.A. RochaR.F. MoreiraJ.C.F. AraújoA.A.S. GelainD.P. Quintans-JúniorL.J. Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol.Basic Clin. Pharmacol. Toxicol.2010107694995710.1111/j.1742‑7843.2010.00609.x20849525
    [Google Scholar]
  72. LimaR.K. CardosoM.G. Família Lamiaceae: Importantes Óleos Essenciais com Ação Biológica e Antioxidante.Revista Fitos200733142410.32712/2446‑4775.2007.78
    [Google Scholar]
  73. PerumalS.S. ShanthiP. SachdanandamP. Combined efficacy of tamoxifen and coenzyme Q10 on the status of lipid peroxidation and antioxidants in DMBA induced breast cancer.Mol. Cell. Biochem.20052731-215116010.1007/s11010‑005‑0325‑316013450
    [Google Scholar]
  74. MassacciA. NabievS.M. PietrosantiL. NematovS.K. ChernikovaT.N. ThorK. LeipnerJ. Response of the photosynthetic apparatus of cotton (Gossypium hirsutum) to the onset of drought stress under field conditions studied by gas-exchange analysis and chlorophyll fluorescence imaging.Plant Physiol. Biochem.200846218919510.1016/j.plaphy.2007.10.00618053735
    [Google Scholar]
  75. Lopez-HuertasE. CharltonW.L. JohnsonB. GrahamI.A. BakerA. Stress induces peroxisome biogenesis genes.EMBO J.200019246770677710.1093/emboj/19.24.677011118212
    [Google Scholar]
  76. NordbergJ. ArnérE.S.J. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system1 1This review is based on the licentiate thesis “Thioredoxin reductase—interactions with the redox active compounds 1-chloro-2,4-dinitrobenzene and lipoic acid” by Jonas Nordberg, 2001, Karolinska Institute, Stockholm, ISBN 91-631-1064-4.Free Radic. Biol. Med.200131111287131210.1016/S0891‑5849(01)00724‑911728801
    [Google Scholar]
  77. RoccoL. MottolaF. SantonastasoM. SaputoV. CusanoE. CostagliolaD. SueroT. PacificoS. StingoV. Anti-genotoxic ability of α-tocopherol and Anthocyanin to counteract fish DNA damage induced by musk xylene.Ecotoxicology20152492026203510.1007/s10646‑015‑1538‑126407710
    [Google Scholar]
  78. PackerL. WeberS.U. RimbachG. Molecular aspects of α-tocotrienol antioxidant action and cell signalling.J. Nutr.20011312369S373S10.1093/jn/131.2.369S11160563
    [Google Scholar]
  79. AzziA. Molecular mechanism of α-tocopherol action.Free Radic. Biol. Med.2007431162110.1016/j.freeradbiomed.2007.03.01317561089
    [Google Scholar]
  80. AzziA. BreyerI. FeherM. PastoriM. RicciarelliR. SpycherS. StaffieriM. StockerA. ZimmerS. ZinggJ.M. Specific cellular responses to α-tocopherol.J. Nutr.200013071649165210.1093/jn/130.7.164910867030
    [Google Scholar]
  81. Ayed-BoussemaI. AbassiH. BouazizC. HlimaW.B. AyedY. BachaH. Antioxidative and antigenotoxic effect of vitamin E against patulin cytotoxicity and genotoxicity in HepG2 cells.Environ. Toxicol.201328629930610.1002/tox.2072021656641
    [Google Scholar]
  82. KianiA.K. PhebyD. HenehanG. BrownR. SievingP. SykoraP. MarksR. FalsiniB. CapodicasaN. MiertusS. LorussoL. DondossolaD. TartagliaG.M. ErgorenM.C. DundarM. MicheliniS. MalacarneD. BonettiG. DautajA. DonatoK. MedoriM.C. BeccariT. SamajaM. ConnellyS.T. MartinD. MorresiA. BacuA. HerbstK.L. KapustinM. StuppiaL. LumerL. FarronatoG. BertelliM. INTERNATIONAL BIOETHICS STUDY GROUP Ethical considerations regarding animal experimentation.J. Prev. Med. Hyg.2022632Suppl. 3E255E26636479489
    [Google Scholar]
  83. TyagiN. KumarS. GangenahalliG. VermaY.K. Computational methods (in silico) and stem cells as alternatives to animals in research.Chemoinformatics and Bioinformatics in the Pharmaceutical Sciences.Academic Press20213894210.1016/B978‑0‑12‑821748‑1.00003‑8
    [Google Scholar]
  84. KaulR. SwaminathanS. KumarV. Need for alternatives to animals in experimentation: An Indian perspective.Indian J. Med. Res.2019149558459210.4103/ijmr.IJMR_2047_1731417025
    [Google Scholar]
/content/journals/cnt/10.2174/0126659786331452241101053153
Loading
/content/journals/cnt/10.2174/0126659786331452241101053153
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test