Abstract
It is claimed that oxidative stress has a prominent role in the mechanism of toxic effects formed by glyphosate-based herbicide (GBH) in living systems. A strong thiol compound, N-acetylcysteine (NAC), has antioxidative and cytoprotective properties. The objective in this subchronic toxicity study was to identify the prophylactic effect of NAC over histopathological changes and oxidative stress induced by GBH in blood, renal, liver, cardiac, and brain tissues. A sum of 28 male Wistar rats were divided into four equal groups, each containing 7 rats. During the study, group I (control group) was supplied with normal rodent bait and tap water ad libitum. The applied agents were 160 mg/kg NAC to group II, 375 mg/kg as equivalent to 1/10 of lethal dose 50% (LD50) of GBH to group III, and 160 mg/kg of NAC and 375 mg/kg of GBH together once per day as oral gavage to group IV for 8 weeks. While GBH decreased the levels of GSH in blood, liver, kidney, and brain tissues, it considerably increased malondialdehyde levels. On the contrary, these parameters happened to improve in the group supplied with NAC. Besides, it was seen that NAC was observed to improve the histopathologic changes in rat tissues induced by GBH. It was concluded that NAC protects oxidative stress and tissue damage induced by GBH in blood and tissue and this prophylactic effect could be attributed to its antioxidant and free radical sweeper character.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abdel-Daim MM, Dessouki AA, Abdel-Rahman HG, Eltaysh R, Alkahtani S (2019) Hepatorenal protective effects of taurine and N-acetylcysteine against fipronil-induced injuries: the antioxidant status and apoptotic markers expression in rats. Sci Total Environ 650:2063–2073. https://doi.org/10.1016/j.scitotenv.2018.09.313
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3
Akbel E, Arslan-Acaroz D, Demirel HH, Kucukkurt I, Ince S (2018) The subchronic exposure to malathion, an organophosphate pesticide, causes lipid peroxidation, oxidative stress, and tissue damage in rats: the protective role of resveratrol. Toxicol Res (Camb) 7:503–512. https://doi.org/10.1039/c8tx00030a
Aksoy Y (2002) Antioksidan Mekanizmada Glutatyonun Rolü. T Klin J Med Sci 22:442–448
Alp H, Pinar N, Dokuyucu R, Kaplan I, Sahan M, Senol S, Karakus A, Yaldiz M (2016) Effects of intralipid and caffeic acid phenyl esther (CAPE) against hepatotoxicity and nephrotoxicity caused by glyphosate isopropylamine (GI). Eur J Inflamm 14:3–9. https://doi.org/10.1177/1721727X16630318
Bai SH, Ogbourne SM (2016) Glyphosate: environmental contamination, toxicity and potential risks to human health via food contamination. Environ Sci Pollut Res 23:18988–19001. https://doi.org/10.1007/s11356-016-7425-3
Benedetti AL, Vituri CDL, Trentin AG et al (2004) The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate-Biocarb®. Toxicol Lett 153:227–232. https://doi.org/10.1016/j.toxlet.2004.04.008
Beutler E (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
Burella PM, Odetti LM, Simoniello MF, Poletta GL (2018) Oxidative damage and antioxidant defense in Caiman latirostris (broad-snouted caiman) exposed in ovo to pesticide formulations. Ecotoxicol Environ Saf 161:437–443. https://doi.org/10.1016/j.ecoenv.2018.06.006
Çaǧlar S, Kolankaya D (2008) The effect of sub-acute and sub-chronic exposure of rats to the glyphosate-based herbicide Roundup. Environ Toxicol Pharmacol 25:57–62. https://doi.org/10.1016/j.etap.2007.08.011
Cattaneo R, Clasen B, Loro VL, de Menezes CC, Pretto A, Baldisserotto B, Santi A, de Avila LA (2011) Toxicological responses of Cyprinus carpio exposed to a commercial formulation containing glyphosate. Bull Environ Contam Toxicol 87:597–602. https://doi.org/10.1007/s00128-011-0396-7
Cattani D, de Liz Oliveira Cavalli VL, Heinz Rieg CE, et al (2014) Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: involvement of glutamate excitotoxicity. Toxicology. https://doi.org/10.1016/j.tox.2014.03.001, 320, 34, 45
Çavuşoğlu K, Yapar K, Oruç E, Yalçın E (2011) Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice. J Med Food 14:1263–1272. https://doi.org/10.1089/jmf.2010.0202
Chłopecka M, Mendel M, Dziekan N, Karlik W (2014) Glyphosate affects the spontaneous motoric activity of intestine at very low doses - in vitro study. Pestic Biochem Physiol 113:25–30. https://doi.org/10.1016/j.pestbp.2014.06.005
Dar MA, Sultana M, Mir AH, Bhat MA, Wani TA, Haq Z (2018) Sub-acute oral toxicity of Roundup® and ammonium nitrate with special reference to oxidative stress indices in wistar rats. Indian J Anim Res 52:405–408. https://doi.org/10.18805/ijar.v0iOF.7826
de Souza JS, Kizys MML, da Conceição RR, Glebocki G, Romano RM, Ortiga-Carvalho TM, Giannocco G, da Silva IDCG, Dias da Silva MR, Romano MA, Chiamolera MI (2017) Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats. Toxicology 377:25–37. https://doi.org/10.1016/j.tox.2016.11.005
Dodd S, Dean O, Copolov DL, Malhi GS, Berk M (2008) N -acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther 8:1955–1962. https://doi.org/10.1517/14728220802517901
Drabkin DL, Austin JH (1935) Spectrophotometric studies. J Biol Chem 112:51–65
Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431. https://doi.org/10.1016/0076-6879(90)86135-I
El-Bini Dhouib I, Annabi A, Jrad A et al (2015) Carbosulfan-induced oxidative damage following subchronic exposure and the protective effects of N-acetylcysteine in rats. Gen Physiol Biophys 34:249–261. https://doi.org/10.4149/gpb_2015005
El-Shenawy NS (2009) Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate. Environ Toxicol Pharmacol 28:379–385. https://doi.org/10.1016/j.etap.2009.06.001
Eraslan G, Kanbur M, Siliğ Y, Karabacak M, Soyer Sarica Z, Şahin S (2016) The acute and chronic toxic effect of cypermethrin, propetamphos, and their combinations in rats. Environ Toxicol 31:1415–1429. https://doi.org/10.1002/tox.22147
Gibson-Corley KN, Olivier AK, Meyerholz DK (2013) Principles for valid histopathologic scoring in research. Vet Pathol 50:1007–1015. https://doi.org/10.1177/0300985813485099
Gress S, Lemoine S, Séralini GE, Puddu PE (2015) Glyphosate-based herbicides potently affect cardiovascular system in mammals: review of the literature. Cardiovasc Toxicol 15:117–126. https://doi.org/10.1007/s12012-014-9282-y
Gultekin F, Delibas N, Yasar S, Kilinc I (2001) In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats. Arch Toxicol 75:88–96. https://doi.org/10.1007/s002040100219
Guyton KZ, Loomis D, Grosse Y, el Ghissassi F, Benbrahim-Tallaa L, Guha N, Scoccianti C, Mattock H, Straif K, International Agency for Research on Cancer Monograph Working Group, IARC, Lyon, France (2015) Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncol 16:490–491. https://doi.org/10.1016/S1470-2045(15)70134-8
Hamdaoui L, Naifar M, Mzid M, Ben Salem M, Chtourou A, Makni-Ayadi F, Sahnoun Z, Rebai T (2016) Nephrotoxicity of Kalach 360 SL: biochemical and histopathological findings. Toxicol Mech Methods 26:685–691. https://doi.org/10.1080/15376516.2016.1230918
Hurst GA, Shaw PB, LeMaistre CA (1967) Laboratory and clinical evaluation of the mucolytic properties of acetylcysteine. Am Rev Respir Dis 96:962–970. https://doi.org/10.1164/arrd.1967.96.5.962
Ince S, Kucukkurt I, Demirel HH, Turkmen R, Sever E (2012) Thymoquinone attenuates cypermethrin induced oxidative stress in Swiss albino mice. Pestic Biochem Physiol 104:229–235. https://doi.org/10.1016/j.pestbp.2012.09.003
Ince S, Kucukkurt I, Demirel HH, Turkmen R, Zemheri F, Akbel E (2013) The role of thymoquinone as antioxidant protection on oxidative stress induced by imidacloprid in male and female Swiss albino mice. Toxicol Environ Chem 95:318–329. https://doi.org/10.1080/02772248.2013.764672
Jasper R, Locatelli GO, Pilati C, Locatelli C (2012) Evaluation of biochemical, hematological and oxidative parameters in mice exposed to the herbicide glyphosate-Roundup®. Interdiscip Toxicol 5:133–140. https://doi.org/10.2478/v10102-012-0022-5
Kamboj A, Kumaresan N, Kiran R, Sandhir R (2006) Neuroprotective potential of N-acetylcysteine in carbofuran neurotoxicity: a biochemical and histopathological study. Toxicol Environ Chem 88:745–753. https://doi.org/10.1080/02772240600934990
Lajmanovich RC, Attademo AM, Simoniello MF, Poletta GL, Junges CM, Peltzer PM, Grenón P, Cabagna-Zenklusen MC (2015) Harmful effects of the dermal intake of commercial formulations containing chlorpyrifos, 2,4-D, and glyphosate on the common toad Rhinella arenarum (Anura: Bufonidae). Water Air Soil Pollut 226. https://doi.org/10.1007/s11270-015-2695-9
Lasram MM, Lamine AJ, Dhouib IB, Bouzid K, Annabi A, Belhadjhmida N, Ahmed MB, el Fazaa S, Abdelmoula J, Gharbi N (2014) Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats. Life Sci 107:50–58. https://doi.org/10.1016/j.lfs.2014.04.033
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Luck H (1965) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 885–894. https://doi.org/10.1016/B978-0-12-395630-9.50158-4
Mañas F, Peralta L, Raviolo J, Ovando HG, Weyers A, Ugnia L, Cid MG, Larripa I, Gorla N (2009) Genotoxicity of glyphosate assessed by the comet assay and cytogenetic tests. Environ Toxicol Pharmacol 28:37–41. https://doi.org/10.1016/j.etap.2009.02.001
Mesnage R, Defarge N, Spiroux de Vendômois J, Séralini GE (2015) Potential toxic effects of glyphosate and its commercial formulations below regulatory limits. Food Chem Toxicol 84:133–153. https://doi.org/10.1016/j.fct.2015.08.012
Mohammadi-Sardoo M, Mandegary A, Nabiuni M, Nematollahi-Mahani SN, Amirheidari B (2018) Mancozeb induces testicular dysfunction through oxidative stress and apoptosis: protective role of N-acetylcysteine antioxidant. Toxicol Ind Health 34:798–811. https://doi.org/10.1177/0748233718778397
Moon JM, Chun BJ, Cho YS, Lee SD, Hong YJ, Shin MH, Jung EJ, Ryu HH (2018) Cardiovascular effects and fatality may differ according to the formulation of glyphosate salt herbicide. Cardiovasc Toxicol 18:99–107. https://doi.org/10.1007/s12012-017-9418-y
Murussi CR, Costa MD, Leitemperger JW, Guerra L, Rodrigues CCR, Menezes CC, Severo ES, Flores-Lopes F, Salbego J, Loro VL (2016) Exposure to different glyphosate formulations on the oxidative and histological status of Rhamdia quelen. Fish Physiol Biochem 42:445–455. https://doi.org/10.1007/s10695-015-0150-x
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3
Pal S, Chatterjee AK (2004) Protective effect of N-acetylcysteine against arsenic-induced depletion in vivo of carbohydrate. Drug Chem Toxicol 27:179–189
Piola L, Fuchs J, Oneto ML, Basack S, Kesten E, Casabé N (2013) Comparative toxicity of two glyphosate-based formulations to Eisenia andrei under laboratory conditions. Chemosphere. 91:545–551. https://doi.org/10.1016/j.chemosphere.2012.12.036
Prescott LF (1983) New approaches in managing drug overdosage and poisoning. Br Med J 287:274–276
Roy NM, Carneiro B, Ochs J (2016) Glyphosate induces neurotoxicity in zebrafish. Environ Toxicol Pharmacol 42:45–54. https://doi.org/10.1016/j.etap.2016.01.003
Samsel A, Seneff S (2013) Glyphosate, pathways to modern diseases II: celiac sprue and gluten intolerance. Interdiscip Toxicol 6:159–184. https://doi.org/10.2478/intox-2013-0026
Samsel A, Seneff S (2015) Glyphosate, pathways to modern diseases III: manganese, neurological diseases, and associated pathologies. Surg Neurol Int 6:45. https://doi.org/10.4103/2152-7806.153876
Sun YI, Oberley L w, Ying L (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500. https://doi.org/10.1074/jbc.M113.471342
Tizhe EV, Ibrahim NDG, Fatihu MY et al (2013) Haematogical changes induced by subchronic glyphosate exposure: ameliorative effect of zinc in Wistar rats. 11:28–35. https://doi.org/10.4314/sokjvs.v11i2.5
Tizhe EV, Ibrahim NDG, Fatihu MY, Onyebuchi II, George BDJ, Ambali SF, Shallangwa JM (2014) Influence of zinc supplementation on histopathological changes in the stomach, liver, kidney, brain, pancreas and spleen during subchronic exposure of Wistar rats to glyphosate. Comp Clin Pathol 23:1535–1543
USEPA (2016) Report on the 2016 U.S. Environmental Protection Agency (EPA) International Decontamination Research and Development Conference
Webster TMU, Santos EM (2015) Global transcriptomic profiling demonstrates induction of oxidative stress and of compensatory cellular stress responses in brown trout exposed to glyphosate and Roundup. BMC Genomics 16:32. https://doi.org/10.1186/s12864-015-1254-5
Whitehouse L, Wong L, Paul C (1985) Postabsorption antidotal effects of N-acetylcysteine on acetaminophen-induced hepatotoxicity in the mouse. Can J Physiol Pharmacol 63:431–437
Winterbourn CC, Hawkins RE, Brian MCR (1975) The estimation of red cell superoxide dismutase activity. J Lab Clin Med 85:337–341
Wunnapuk K, Gobe G, Endre Z, Peake P, Grice JE, Roberts MS, Buckley NA, Liu X (2014) Use of a glyphosate-based herbicide-induced nephrotoxicity model to investigate a panel of kidney injury biomarkers. Toxicol Lett 225:192–200. https://doi.org/10.1016/j.toxlet.2013.12.009
Yarsan E, Tanyuksel M, Celik S, Aydin A (1999) Effects of aldicarb and malathion on lipid peroxidation. Bull Environ Contam Toxicol 63:575–581. https://doi.org/10.1007/s001289901019
Youness A, El-Toukhy et al (2016) The protective effect of orange juice on glyphosate toxicity in adult male mice. J Chem Pharm Res 8:13–28
Yurumez Y, Cemek M, Yavuz Y, Birdane YO, Buyukokuroglu ME (2007) Beneficial effect of N-acetylcysteine against organophosphate toxicity in mice. Biol Pharm Bull 30:490–494. https://doi.org/10.1248/bpb.30.490
Acknowledgements
A short summary of this study was verbally presented at I. International Congress on Medicinal and Aromatic Plants, 09–12 May 2017, in Konya, Turkey.
Funding
This study was funded by Afyon Kocatepe University Scientific Research Projects Coordination Department (Project No: 16.VF.11).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Responsible editor: Philippe Garrigues
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Turkmen, R., Birdane, Y.O., Demirel, H.H. et al. Antioxidant and cytoprotective effects of N-acetylcysteine against subchronic oral glyphosate-based herbicide-induced oxidative stress in rats. Environ Sci Pollut Res 26, 11427–11437 (2019). https://doi.org/10.1007/s11356-019-04585-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-019-04585-5