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Sub-chronic exposure to Kalach 360 SL–induced damage in rats’ liver and hematological system

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Abstract

We investigated the effects of sub-chronic exposure to Kalach 360 SL (KL), glyphosate-based herbicide used in Tunisia, on liver and hematological system in different groups of female rats. Group 1 was used as a control, while animals of groups 2 and 3 received orally 0.07 mL and 0.175 mL of KL, respectively (126 and 315 mg of glyphosate/kg), for 60 days. As a result, the KL-exposed groups exhibited hypochromic microcytic anemia, systemic inflammation, cytolysis, decrease in hepatic enzyme activity, and cholestasis. Exposure to different doses of KL could induce erythrocyte destruction (hemolysis) in hematopoietic organs (bones). Moreover, lipid peroxidation contents and protein oxidation markers significantly increased in exposed groups, while enzymatic and non-enzymatic antioxidant activities decreased considerably, in both erythrocytes and liver tissues, compared with those in controls. Liver histological studies confirmed the presence of inflammatory reaction with pathology involving the damage or necrosis of hepatocytes, however, without fibrosis remodulation. Thus, KL sub-chronic exposure caused hepatonecrosis, systemic inflammation, and hemolysis.

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Abbreviations

ALT:

Alanine aminotransferase

AOPP:

Oxidation protein product

AST:

Aspartate aminotransferase

BW:

Bodyweight

CAT:

Catalase

CRP:

C-reactive protein

D1:

Dose 1

D2:

Dose 2

DNA:

Deoxyribonucleic acid

G:

Glyphosate

GSH:

Reduced glutathione

Hb:

Hemoglobin

H2O2 :

Hydrogen peroxide

H&E:

Hematoxylin–eosin

KL:

Kalach

LD50:

Lethal dose

LDH:

Lactate deshydrogenase

MDA:

Malondialdehyde

MCH:

Mean corpuscular hemoglobin

MCHC:

Mean corpuscular hemoglobin concentration

PAL:

Alcaline phosphatase

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

Vit C:

Vitamin C

VGM:

Mean corpuscular volume

WBC:

White blood cell

References

  • Abdel-Daim MM, Abdeen A (2018) Protective effects of rosuvastatin and vitamin E against fipronil-mediated oxidative damage and apoptosis in rat liver and kidney. Food Chem Toxicol 114:69–77

    CAS  Google Scholar 

  • Abdel-Daim MM, Abdellatief SA (2018) Attenuating effects of caffeic acid phenethyl ester and betaine on abamectin-induced hepatotoxicity and nephrotoxicity. Environ Sci Pollut Res 25:15909–15917

    CAS  Google Scholar 

  • Abdel-Daim MM, Abuzead SM, Halawa SM (2013) Protective role of Spirulina platensis against acute deltamethrin-induced toxicity in rats. PLoS One 8:e72991

    CAS  Google Scholar 

  • Abdel-Daim MM, Abd Eldaim MA, Mahmoud MM (2014) Trigonella foenum-graecum protection against deltamethrin-induced toxic effects on haematological, biochemical, and oxidative stress parameters in rats. Can J Physiol Pharmacol 92:679–685. https://doi.org/10.1139/cjpp-2014-0144

    Article  CAS  Google Scholar 

  • Abdel-Daim MM, Taha R, Ghazy EW, El-Sayed YS (2016a) Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies. Can J Physiol Pharmacol 94:81–88

    CAS  Google Scholar 

  • Abdel-Daim M, El-Bialy BE, Abdel Rahman HG, Radi AM, Hefny HA, Hassan AM (2016b) Antagonistic effects of Spirulina platensis against sub-acute deltamethrin toxicity in mice: biochemical and histopathological studies. Biomed Pharmacother 77:79–85

    CAS  Google Scholar 

  • Abdel-Daim MM, Abushouk AI, Alkhalf MI, Toraih EA, Fawzy MS, Ijaz H, Bungau SG (2018a) Antagonistic effects of Spirulina platensis on diazinon-induced hemato-biochemical alterations and oxidative stress in rats. Environ Sci Pollut Res 25:27463–27470

    CAS  Google Scholar 

  • Abdel-Daim MM, Shaheen HM, Abushouk AI, Toraih EA, Fawzy MS, Alansari WS, Bungau S (2018b) Thymoquinone and diallyl sulfide protect against fipronil-induced oxidative injury in rats. Environ Sci Pollut Res 25:23909–23916

    CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Abdelkhalek NKM, Eissa IAM, Ahmed E, Kilany OE, El-Adl M, Dawood MAO, Hassan AM, Abdel-Daim MM (2017) Protective role of dietary Spirulina platensis against diazinon-induced oxidative damage in Nile tilapia; Oreochromis niloticus. Environ Toxicol Pharmacol 54:99–104

    CAS  Google Scholar 

  • Abdollahi M, Mostafalou S, Pourn Ourmo Hammadi S, Shadnia S (2004) Oxidative stress and cholinesterase inhibition in saliva and plasma of rats following subchronic exposure to malathion. Comp Biochem Phya Part C 137:29–34

    Google Scholar 

  • Abdou RH, Abdel-Daim MM (2014) Alpha-lipoic acid improves acute deltamethrin-induced toxicity in rats. Can J Physiol Pharmacol 92:773–779

    CAS  Google Scholar 

  • Acquavella JF, Bruce H, Alexander BH, Mandel JS, Gustin C, Baker B, Champan P, Bleeke M (2004) Glyphosate biomonitoring for farmers and their families: results from the farm family exposure study. Environ Health Perspect 112:321–326

    CAS  Google Scholar 

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:21–126

    Google Scholar 

  • Astiz M, de Alaniz MJ, Marra CA (2009) Effect of pesticides on cell survival in liver and brain rat tissues. Ecotoxicol Environ Saf 72:2025–2032

    CAS  Google Scholar 

  • Ayansina ADV, Oso BA (2006) Effect of two commonly used herbicides on soil microflora at two different concentrations. Afr J Biotechnol 5:129–132

    CAS  Google Scholar 

  • Beauchamp C, Fridovich I (1971) Superoxydedimutase: improved assays and an assay applicable to acrylamide gel. Anal Biochem 44:276–287

    CAS  Google Scholar 

  • Benachour N, Seralini GE (2009) Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental. Cell Chem Resea Toxicol 22:97–105

    CAS  Google Scholar 

  • Benedetti AL, de Lourdes Vituri C, Trentin AG, Domingues MAC, Alvarez-Silva M (2004) The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate-Biocarb®. Toxicol Lett 153:227–232

    CAS  Google Scholar 

  • Bradford M (1976) A rapid and sensitive method for the quantities of microgram quantities of protein utilizing the principal of protein binding. Anal Biochem 72:248–254

    CAS  Google Scholar 

  • Bukowska B, Pieniaz zek D, Duda W (2002) Effect of Roundup on human erythrocytes. Cell Mol Biol Lett 26:245–249

    CAS  Google Scholar 

  • Cağlar 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

    Google Scholar 

  • Camaschella C (2015) Iron-deficiency anemia. New England J Med Surg Collat Branches Sci 372:1832–1843

    Google Scholar 

  • Claster S, Chiu DT, Quintanilha A, Lubin B (1984) Neutrophils mediate lipid peroxidation in human red cells. Blood 64:1079–1084

    CAS  Google Scholar 

  • Contardo-Jara V, Klingelmann E, Wiegand C (2008) Bioaccumulation of glyphosate and its formulation Roundup in lumbriculus variegatus and its effects on bio- transformation and antioxidant enzymes. Environ Pollut 157:57–63

    Google Scholar 

  • Dallegrave E, Mantese FD, Coelho RS, Pereira JD, Dalsenter PR, Langeloh A (2003) The teratogenic potential of the herbicide glyphosate-Roundup in Wistar rats. Toxicol Lett 142:45–52

    CAS  Google Scholar 

  • Dallegrave E, Mantese FD, Oliveira RT, Andrade AJ, Dalsenter PR, Langeloh A (2007) Pre-and postnatal toxicity of the commercial glyphosate formulation in Wistar rats. Arch Toxicol 81:665–673

    CAS  Google Scholar 

  • De Boer WB, Segal A, Frost FA, Sterrett GF (2000) Can CD34 discriminate between benign and malignant hepatocytic lesions in fine-needle aspirates and thin core biopsies. Cancer 90:273–278

    Google Scholar 

  • Decker K (1998) The response of liver macrophages to inflammatory stimulation. Keio J Med 47:1–9

    CAS  Google Scholar 

  • DIREN (2006) Ile de France Pesticide Investigation. In: Regional Environmental Office of Ile De France, Paris, p 26

  • Do CarmoLangiano V, Martinez CB (2008) Toxicity and effects of a glyphosate-based herbicide on the Neotropical fish Prochilodus lineatus. Comp Biochem Physio Part C: Toxicol Pharmacol 147:222–231

    Google Scholar 

  • Dodge JT, Mitchell C, Hanahan DJ (1963) The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Archi Biochem Biophy 100:119–130

    CAS  Google Scholar 

  • Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation Methods Enzymol 186:421–431

    CAS  Google Scholar 

  • Dubois A, Lacouture L (2011) Bilan de présence des micropolluants dans les milieux aquatiques continentaux Période 2007–2009. Commissariat général au développement durable – Service de l’observation et des statistiques.

  • El-Demerdash FM (2004) Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme activities and biochemical parameters in rats exposed to aluminium. J Trace Elem Med Biol 18:113–121

    CAS  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    CAS  Google Scholar 

  • El-Shenawy NS (2009) Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate. Environ Toxicol Pharmacol 28:379–385

    CAS  Google Scholar 

  • Emam H, Ahmed E, Abdel-Daim M (2018) Antioxidant capacity of omega-3-fatty acids and vitamin E against imidacloprid-induced hepatotoxicity in Japanese quails. Environ Sci Pollut Res 25:11694–11702

    CAS  Google Scholar 

  • Fakoya FA (2002) Reticulin fibres in the tunica albuginea and peritubular tissue of seminiferous tubules of adult male Wistar rats. Acta Histochem 104:279–283

    Google Scholar 

  • Gehin A, Guyon C, Nicod L (2005) Glyphosate-induced antioxidant imbalance in HaCaT: the protective effect of vitamins C and E. Environ Toxicol Pharmacol 22:27–34

    Google Scholar 

  • Gianella P, Martin PY, Stucker F (2013) Prise en charge de l’anémie rénale en 2013. Rev Med Suisse 9:462–467

    CAS  Google Scholar 

  • Goto M, Lemasters JJ, Thurman RG (1993) Activation of voltage-dependent calcium channels in Kupffer cells by chronic treatment with alcohol in the rat. J Pharmacol Exp Ther 267:1264–1268

    CAS  Google Scholar 

  • Goto S, Deguchi J, Nishio N, Nomura N, Funabashi H (2015) Hepatotoxicants induce cytokine imbalance in response to innate immune system. J Toxicol Sci 40:389–404

    CAS  Google Scholar 

  • Hamdaoui L, Naifar M, Mzid M, Ben Salem M, Chtourou A, Ayadi-Makni F, Sahnoun Z, Rebai T (2016) Nephrotoxicity of Kalach 360 SL: biochemical and histopathological findings. Toxicol Mech Meths 26:685–691

    CAS  Google Scholar 

  • Hamdaoui L, Naifar M, Rahmouni F, Harrabi B, Ayadi F, Sahnoun Z, Rebai T (2018) Subchronic exposure to Kalach 360 SL-induced endocrine disruption and ovary damage in female rats. Arch Physiol Biochem 124:27–34

    CAS  Google Scholar 

  • Jacques-Silva MC, Nogueira CW, Broch LC, Flores ÉM, Rocha JBT (2001) Diphenyl diselenide and ascorbic acid changes deposition of selenium and ascorbic acid in liver and brain of mice. Basic Clin Pharmacol Toxicol 88:119–125

    CAS  Google Scholar 

  • Jollow DJ, Mitchell JR, Zamppaglione Z, Gillette JR (1974) Bromobenzene induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolites. Pharmacology 11:151–157

    CAS  Google Scholar 

  • Kayali R, Çakatay U, Akçay T, Altuğ T (2006) Effect of alpha-lipoic acid supplementation on markers of protein oxidation in post-mitotic tissues of ageing rat. Cell Biochem Funct 24:79–85

    CAS  Google Scholar 

  • Kongsong P, Sikong L, Niyomwas S, Rachpech V (2014) Photocatalytic degradation of glyphosate in water by N-doped SnO2/TiO2 thin film coated glass fibers. Photochemphotobiol 90:1243–1250

    CAS  Google Scholar 

  • Larsen K, Najle R, Lifschitz A, Virkel G (2012) Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine. Environ Toxicol Pharmacol 34:811–818

    CAS  Google Scholar 

  • Lin V, Garry V (2000) In vitro studies of cellular and molecular development toxicity of adjuvants, herbicides, and fungicides commonly used in Red River Valley. J Toxicol Environ Health A 60:423–439

    CAS  Google Scholar 

  • Lushchak V, Kubrak OI, Storey JM, Storey KB, Lushchak VI (2009) Low toxic herbicide Roundup induces mild oxidative stress in goldfish tissues. Chemosphere 76:932–937

    CAS  Google Scholar 

  • Mangara A, Kouame NMT, Soro K, N’Da AAA, Gnahoua GM, Soro D (2014) Test d’efficacité d’un herbicide en culture d’ananas et de production d’Anguédédou en Côte d’Ivoire. J Appl Biosci 80:7161–7172

    Google Scholar 

  • Maroni M, Colosio C, Ferioli A, Fait A (2000) Biological monitoring of pesticide exposure: a review. Introduc Toxicol 143:1–118

    CAS  Google Scholar 

  • Nakatani AS, Fernandes MF, de Souza RA, da Silva AP, dos Reis-Junior FB, Mendes IC, Hungria M (2014) Effects of the glyphosate-resistance gene and of herbicides applied to the soybean crop on soil microbial biomass and enzymes. Field Crop Res 162:20–29

    Google Scholar 

  • Pieniazek D, Bukowska B, Duda W (2004) Comparison of the effect of Roundup ultra 360 SL pesticide and its active compound glyphosate on human erythrocytes. Pesti Biochem Physioll 79:58–63

    CAS  Google Scholar 

  • Pincemail J, Bonjean K, Cayeux K, Defraigne JO (2002) Mécanismes physiologiques de la défense antioxydante. Nut Clini Metabol 16:233–239

    CAS  Google Scholar 

  • Quaghebeur D, De Smet B, De Wulf E, Steurbaut W (2004) Pesticides in rainwater in Flanders, Belgium: results from the monitoring program 1997–2001. Environ Health Perspect 6:182–190

    CAS  Google Scholar 

  • Stockham SL, Scott MA (2002) Liver function. Fundamentals of veterinary clinical pathology Blackwell Publishing Ames 461-486.

  • Takahashi M, Horie M, Aoba N (2001) Analysis of glyphosate and its metabolite, aminomethylphosphonic acid, in agricultural products by HPLC. Shokuhin Eiseigaku Zasshi 42:304–308

    CAS  Google Scholar 

  • Tomlin CDS (2006) The pesticide manual: a world compendium, 14th edn. British Crop Protection Council, Hampshire, pp 545–548

    Google Scholar 

  • Turkmen R, Birdane YO, Demirel HH, Kabu HYM, Ince S (2019a) 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

    CAS  Google Scholar 

  • Turkmen R, Birdane YO, Demirel HH, Kabu HYM, Ince S (2019b) Protective effects of resveratrol on biomarkers of oxidative stress, biochemical and histopathological changes induced by sub-chronic oral glyphosate-based herbicide in rats. Toxicol Res 8:238–245

    CAS  Google Scholar 

  • Tuzmen N, Candan N, Kaya E, Demiryas N (2008) Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver. Cell Biochem Funct 26:119–124

    CAS  Google Scholar 

  • Williams GM, Kroes R, Munro IC (2000) Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol 31:117–165

    CAS  Google Scholar 

  • Wunnapuk K, Gobe G, Endre Z, Peake P, Grice JE, RobertsMS BNA, 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

    CAS  Google Scholar 

  • Yousef MI, Salem MH, Ibrahim HZ, Helmi S, Seehy MA, Bertheussen K (1995) Toxic effects of carbofuran and glyphosate on semen characteristics in rabbits. J Environ Sci Health B 30:513–534

    CAS  Google Scholar 

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Acknowledgments

The authors are grateful to Pr. Wassim Hariz and Pr. Kamel Maaloul English Language Teachers at the Faculty of Science of Sfax, for having proofread the manuscript.

Funding

This work was supported by grants from the Tunisian Ministry of Higher Education and Scientific Research and it was carried out in the research unit 12ES15 (previously 99/UR/0860) of the Faculty of Medicine, Sfax.

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Correspondence to Latifa Hamdaoui.

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Our experimental protocol was approved by the Research Ethics Committee and all efforts were made to minimize animal suffering and reduce the number of animals used.

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The authors declare that they have no conflicts of interest.

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Responsible editor: Philippe Garrigues

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Hamdaoui, L., Naifar, M., Rahmouni, F. et al. Sub-chronic exposure to Kalach 360 SL–induced damage in rats’ liver and hematological system. Environ Sci Pollut Res 26, 36634–36646 (2019). https://doi.org/10.1007/s11356-019-06491-2

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