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2000
Volume 20, Issue 1
  • ISSN: 1573-4080
  • E-ISSN:

Abstract

Background

The imbalance between free radical formation and antioxidant defence leads to the development of oxidative stress. The search for substances that would mitigate or prevent the effects of oxidative stress remains relevant.

Objective

Our goal was to compare the antioxidant and mitigation effects of L-glutamic acid (L-Glu) and N-acetylcysteine (NAC) alone or in combination using a battery of biomarkers of oxidative stress such as reduced glutathione (GSH) superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST) and lipid peroxidation, determined as a content of lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS). Histopathological examination of the liver was also performed.

Methods

Experimental rats were divided into five experimental groups. Exp.1: was treated with CCl only, Exp. 2: was treated with CCl/L-Glu, Exp. 3: was treated with CCl/Glu/NAC. Exp. 4: was treated with CCl/NAC, Control 5: served as the control rats.

Results

These findings suggest that the CCl leads to oxidative stress by depleting the antioxidant enzyme activities and increasing peroxidation products. The studied biochemical parameters were altered by the introduction of CCl, which was normalised (to one degree or another) by L-Glu, L-Glu/NAC and NAC treatment.

Conclusion

The most remarkable protective effect was observed in groups of rats that were treated with L-Glu only. This conclusion was confirmed by histopathological findings which showed less severe hepatocellular necrosis, fibrosis and inflammation in CCl/L- Glu and CCl/L-Glu/NAC treated group, compared to the CCl group.

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References

  1. SiesH. BerndtC. JonesD.P. Oxidative stress.Annu. Rev. Biochem.201786171574810.1146/annurev‑biochem‑061516‑045037 28441057
    [Google Scholar]
  2. PisoschiA.M. PopA. The role of antioxidants in the chemistry of oxidative stress: A review.Eur. J. Med. Chem.201597557410.1016/j.ejmech.2015.04.040 25942353
    [Google Scholar]
  3. LoboV. PatilA. PhatakA. ChandraN. Free radicals, antioxidants and functional foods: Impact on human health.Pharmacogn. Rev.20104811812610.4103/0973‑7847.70902 22228951
    [Google Scholar]
  4. LiS. TanH.Y. WangN. The role of oxidative stress and antioxidants in liver diseases.Int. J. Mol. Sci.20151611260872612410.3390/ijms161125942 26540040
    [Google Scholar]
  5. Cichoż-LachH. MichalakA. Oxidative stress as a crucial factor in liver diseases.World J. Gastroenterol.201420258082809110.3748/wjg.v20.i25.8082 25009380
    [Google Scholar]
  6. GaucherC. BoudierA. BonettiJ. ClarotI. LeroyP. ParentM. Glutathione: Antioxidant properties dedicated to nanotechnologies.Antioxidants2018756210.3390/antiox7050062 29702624
    [Google Scholar]
  7. LuS.C. Glutathione synthesis.Biochim. Biophys. Acta, Gen. Subj.2013183053143315310.1016/j.bbagen.2012.09.008 22995213
    [Google Scholar]
  8. RosalovskyV.P. Effect of 5-day exposure of vitamin A and E on status of red blood cell antioxidant system and hematological parameters of rats intoxicated by chlorpyrifos.Anim. Biol. Leiden Neth.201719210611410.15407/animbiol19.02.106
    [Google Scholar]
  9. MaríM. MoralesA. ColellA. García-RuizC. KaplowitzN. Fernández-ChecaJ.C. Mitochondrial glutathione: Features, regulation and role in disease.Biochim. Biophys. Acta, Gen. Subj.2013183053317332810.1016/j.bbagen.2012.10.018 23123815
    [Google Scholar]
  10. RibasV. García-RuizC. Fernández-ChecaJ.C. Glutathione and mitochondria.Front. Pharmacol.2014515110.3389/fphar.2014.00151 25024695
    [Google Scholar]
  11. SiesH. Oxidative stress: A concept in redox biology and medicine.Redox Biol.2015418018310.1016/j.redox.2015.01.002 25588755
    [Google Scholar]
  12. AoyamaK. NakakiT. Glutathione in cellular redox homeostasis: Association with the excitatory amino acid carrier 1 (EAAC1).Molecules20152058742875810.3390/molecules20058742 26007177
    [Google Scholar]
  13. CommandeurJ.N. StijntjesG.J. VermeulenN.P. Enzymes and transport systems involved in the formation and disposition of glutathione S-conjugates. Role in bioactivation and detoxication mechanisms of xenobiotics.Pharmacol. Rev.1995472271330 7568330
    [Google Scholar]
  14. BallatoriN KranceSM NotenboomS ShiS TieuK HammondCL Glutathione dysregulation and the etiology and progression of human diseases.bchm 20093903191214
    [Google Scholar]
  15. VairettiM. Di PasquaL.G. CagnaM. RichelmiP. FerrignoA. BerardoC. Changes in glutathione content in liver diseases: An update.Antioxidants202110336410.3390/antiox10030364 33670839
    [Google Scholar]
  16. ReedM.C. ThomasR.L. PavisicJ. JamesS.J. UlrichC.M. NijhoutH.F. A mathematical model of glutathione metabolism.Theor. Biol. Med. Model.200851810.1186/1742‑4682‑5‑8 18442411
    [Google Scholar]
  17. SalyhaN.O. Effects of L-glutamic acid and pyridoxine on glutathione depletion and lipid peroxidation generated by epinephrine-induced stress in rats.Ukr. Biochem. J.201890410211010.15407/ubj90.04.102
    [Google Scholar]
  18. McGillM.R. JaeschkeH. Animal models of drug-induced liver injury.Biochim. Biophys. Acta Mol. Basis Dis.2019186551031103910.1016/j.bbadis.2018.08.037 31007174
    [Google Scholar]
  19. NevzorovaY.A. Boyer-DiazZ. CuberoF.J. Gracia-SanchoJ. Animal models for liver disease – A practical approach for translational re-search.J. Hepatol.202073242344010.1016/j.jhep.2020.04.011 32330604
    [Google Scholar]
  20. AlkinaniK.B. AliE.M.M. Al-ShaikhT.M. Hepatoprotective effects of (−) epicatechin in CCl4-induced toxicity model are mediated via modulation of oxidative stress markers in rats.Evid. Based Complement. Alternat. Med.2021202111210.1155/2021/4655150 34976093
    [Google Scholar]
  21. ZhouY. PengC. ZhouZ. HuangK. Ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver injury in rats by sup-pressing inflammation and oxidative stress.J. Toxicol. Sci.201944640541410.2131/jts.44.405 31168027
    [Google Scholar]
  22. RenX. XinL.T. ZhangM.Q. Hepatoprotective effects of a traditional Chinese medicine formula against carbon tetrachloride-induced hepatotoxicity in vivo and in vitro.Biomed. Pharmacother.201911710919010.1016/j.biopha.2019.109190 31387170
    [Google Scholar]
  23. WangW. JiangL. RenY. ShenM. XieJ. Characterizations and hepatoprotective effect of polysaccharides from Mesona blumes against tetrachloride-induced acute liver injury in mice.Int. J. Biol. Macromol.201912478879510.1016/j.ijbiomac.2018.11.260 30502438
    [Google Scholar]
  24. ErnstL. ZieglowskiL. SchulzM. Severity assessment in mice subjected to carbon tetrachloride.Sci. Rep.20201011579010.1038/s41598‑020‑72801‑1 32978437
    [Google Scholar]
  25. DenizG.Y. LalogluE. KocK. GeyikogluF. Hepatoprotective potential of Ferula communis extract for carbon tetrachloride induced hepato-toxicity and oxidative damage in rats.Biotech. Histochem.201994533434010.1080/10520295.2019.1566831 30712392
    [Google Scholar]
  26. UstunerD. ColakE. DincerM. Posttreatment effects of olea europaea L. leaf extract on carbon tetrachloride-induced liver injury and oxidative stress in rats.J. Med. Food201821989990410.1089/jmf.2017.0143 29648970
    [Google Scholar]
  27. DuttaS. ChakrabortyA.K. DeyP. Chaudhuri amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill.PLoS One2018134130
    [Google Scholar]
  28. LiR. ZhangP. LiC. YangW. YinY. TaoK. Tert-butylhydroquinone mitigates carbon tetrachloride induced hepatic injury in mice.Int. J. Med. Sci.202017142095210310.7150/ijms.45842 32922170
    [Google Scholar]
  29. MohammedM. Nephroprotective effect of zingerone against CCl4-induced renal toxicity in swiss albino mice: Molecular mechanism.Oxid. Med. Cell. Longev.201820182474831
    [Google Scholar]
  30. WuG. LuptonJ.R. TurnerN.D. FangY-Z. YangS. Glutathione metabolism and its implications for health.J. Nutr.2004134348949210.1093/jn/134.3.489 14988435
    [Google Scholar]
  31. GruczaK. ChołbińskiP. KwiatkowskaD. SzutowskiM. Effects of supplementation with glutathione and its precursors on athlete perfor-mance.Biomed. J. Sci. Tech. Res.201912494349441
    [Google Scholar]
  32. MichlinM. Argaev-FrenkelL. Weinstein-FudimL. OrnoyA. RosenzweigT. Maternal N-acetyl cysteine intake improved glucose tolerance in obese mice offspring.Int. J. Mol. Sci.2020216198110.3390/ijms21061981 32183232
    [Google Scholar]
  33. MahmoudS.M. Abdel MoneimA.E. QayedM.M. El-YamanyN.A. Potential role of N-acetylcysteine on chlorpyrifos-induced neurotoxicity in rats.Environ. Sci. Pollut. Res. Int.20192620207312074110.1007/s11356‑019‑05366‑w 31104238
    [Google Scholar]
  34. LiuY. YaoW. XuJ. The anti-inflammatory effects of acetaminophen and N -acetylcysteine through suppression of the NLRP3 inflammasome pathway in LPS-challenged piglet mononuclear phagocytes.Innate Immun.201521658759710.1177/1753425914566205 25575547
    [Google Scholar]
  35. LeeS.I. KangK.S. N-acetylcysteine modulates lipopolysaccharide-induced intestinal dysfunction.Sci. Rep.201991100410.1038/s41598‑018‑37296‑x 30700808
    [Google Scholar]
  36. Sadegh Soltan-SharifiM. MojtahedzadehM. NajafiA. Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms.Hum. Exp. Toxicol.200726969770310.1177/0960327107083452 17984140
    [Google Scholar]
  37. CynoberL. Metabolism of dietary glutamate in adults.Ann. Nutr. Metab.2018735Suppl. 551410.1159/000494776 30508813
    [Google Scholar]
  38. HouY. WuG. l-Glutamate nutrition and metabolism in swine.Amino Acids201850111497151010.1007/s00726‑018‑2634‑3 30116978
    [Google Scholar]
  39. SalyhaN.O. Effect of glutamic acid and cysteine on oxidative stress markers in rats.Ukr. Biochem. J.202092616517210.15407/ubj92.06.165
    [Google Scholar]
  40. HolečekM. Branched-chain amino acids in health and disease: Metabolism, alterations in blood plasma, and as supplements.Nutr. Metab.20181513310.1186/s12986‑018‑0271‑1 29755574
    [Google Scholar]
  41. MagiS. PiccirilloS. AmorosoS. The dual face of glutamate: From a neurotoxin to a potential survival factor—metabolic implications in health and disease.Cell. Mol. Life Sci.20197681473148810.1007/s00018‑018‑3002‑x 30599069
    [Google Scholar]
  42. AlbarracinS.L. BaldeonM.E. SangronisE. PetruschinaA.C. ReyesF.G.R. L-glutamate: A key amino acid for senory and metabolic functions.Arch. Latinoam. Nutr.2016662101112 29737666
    [Google Scholar]
  43. YooH.C. YuY.C. SungY. HanJ.M. Glutamine reliance in cell metabolism.Exp. Mol. Med.20205291496151610.1038/s12276‑020‑00504‑8 32943735
    [Google Scholar]
  44. BallesterM. SentandreuE. LuongoG. Glutamine/glutamate metabolism rewiring in reprogrammed human hepatocyte-like cells.Sci. Rep.20199117978
    [Google Scholar]
  45. ToméD. Te roles of dietary glutamate in the intestine.Ann. Nutr. Metab.2018735Suppl. 5152010.1159/000494777 30508814
    [Google Scholar]
  46. WalkerM.C. van der DonkW.A. The many roles of glutamate in metabolism.J. Ind. Microbiol. Biotechnol.2016432-341943010.1007/s10295‑015‑1665‑y 26323613
    [Google Scholar]
  47. XueH. FieldC.J. New role of glutamate as an immunoregulator via glutamate receptors and transporters.Front. Biosci.2011S311007102010.2741/205 21622250
    [Google Scholar]
  48. SalyhaN. SalyhaY. Protective role of l-glutamic acid and l-cysteine in mitigation the chlorpyrifos-induced oxidative stress in rats.Environ. Toxicol. Pharmacol.20186415516310.1016/j.etap.2018.10.010 30412861
    [Google Scholar]
  49. TabassumS. AhmadS. MadihaS. Free l-glutamate-induced modulation in oxidative and neurochemical profile contributes to enhancement in locomotor and memory performance in male rats.Sci. Rep.20201011120610.1038/s41598‑020‑68041‑y 32641780
    [Google Scholar]
  50. YoungV.R. AjamiA.M. Glutamate: an amino acid of particular distinction.J. Nutr.20001304Suppl.892S900S10.1093/jn/130.4.892S 10736349
    [Google Scholar]
  51. LiuG. WuX. JiaG. Effects of glutamine against oxidative stress in the metabolome of rats—new insight.RSC Advances2016678745157452410.1039/C6RA14469A
    [Google Scholar]
  52. WindleE.M. Glutamine supplementation in critical illness: Evidence, recommendations, and implications for clinical practice in burn care.J. Burn Care Res.200627676477210.1097/01.BCR.0000245417.47510.9C 17091069
    [Google Scholar]
  53. ZabotG.P. CarvalhalG.F. MarroniN.P. Glutamine prevents oxidative stress in a model of portal hypertension.World J. Gastroenterol.201723254529453710.3748/wjg.v23.i25.4529 28740341
    [Google Scholar]
  54. SchemittE.G. ColaresJ.R. HartmannR.M. Effect of glutamine on oxidative stress and infammation in a rat model of fulminant hepatic failure.Nutr. Hosp.20163392
    [Google Scholar]
  55. SchemittE.G. HartmannR.M. ColaresJ.R. Protective action of glutamine in rats with severe acute liver failure.World J. Hepatol.201911327328610.4254/wjh.v11.i3.273 30967905
    [Google Scholar]
  56. ChenS. XiaY. ZhuG. Glutamine supplementation improves intestinal cell proliferation and stem cell differentiation in weanling mice.Food Nutr. Res.20186206210.29219/fnr.v62.1439 30083086
    [Google Scholar]
  57. DenekeS.M. SteigerV. FanburgB.L. Effect of hyperoxia on glutathione levels and glutamic acid uptake in endothelial cells.J. Appl. Physiol.19876351966197110.1152/jappl.1987.63.5.1966 2891677
    [Google Scholar]
  58. GarlickP.J. Assessment of the safety of glutamine and other amino acids.J. Nutr.20011319Suppl.2556S2561S10.1093/jn/131.9.2556S 11533313
    [Google Scholar]
  59. LeikinJ.B. McFeeR.B. KerscherR. Handbook of nuclear, biological, and chemical agent exposures.CRC Press200710.1201/b14264
    [Google Scholar]
  60. SalyhaN.O. L-glutamic acid effect on changes in biochemical parameters of rats intoxicated by carbon tetrachloride.Anim. Biol. Leiden Neth.2021231182210.15407/animbiol23.01.018
    [Google Scholar]
  61. JegatheeswaranS. SiriwardenaA.K. Experimental and clinical evidence for modification of hepatic ischaemia–reperfusion injury by N-acetylcysteine during major liver surgery.HPB2011132717810.1111/j.1477‑2574.2010.00263.x 21241423
    [Google Scholar]
  62. Lopes-RochaA. BezerraT.O. ZanottoR. Lages NascimentoI. RodriguesA. SalumC. The antioxidant N-Acetyl-L-cysteine restores the behavioral deficits in a neurodevelopmental model of schizophrenia through a mechanism that involves nitric oxide.Front. Pharmacol.20221392495510.3389/fphar.2022.924955 35903343
    [Google Scholar]
  63. Oliveira FilhoL.D. SaadK.R. SaadP.F. KoikeM.K. SilvaS.M. MonteroE.F. Effect of N-acetylcysteine in hearts of rats submitted to con-trolled hemorrhagic shock.Rev. Bras. Cir. Cardiovasc.2015302173181 26107448
    [Google Scholar]
  64. SalyhaN.O. Activity of the glutathione system of antioxidant defense in rats under the action of L-glutamic acid.Ukr. Biochem. J.20138544047
    [Google Scholar]
  65. RosalovskyV.P. GrabovskaS.V. SalyhaY.T. Changes in glutathione system and lipid peroxidation in rat blood during the first hour after chlorpyrifos exposure.Ukr. Biochem. J.201587512413210.15407/ubj87.05.124 26717603
    [Google Scholar]
  66. FerreiraT. RasbandW. ImageJ User Guide.New YorkNational Institute of Health2012
    [Google Scholar]
  67. TeschkeR. Liver injury by carbon tetrachloride intoxication in 16 patients treated with forced ventilation to accelerate toxin removal via the lungs: A clinical report.Toxics2018622510.3390/toxics6020025 29702608
    [Google Scholar]
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  • Article Type:
    Research Article
Keyword(s): antioxidant system; free radicals; L-Glu; NAC; Oxidative stress; xenobiotics
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