Skip to main content
SpringerLink
Log in

Protective effects of rutin against deltamethrin-induced hepatotoxicity and nephrotoxicity in rats via regulation of oxidative stress, inflammation, and apoptosis

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Deltamethrin is a type-II pyrethroid synthetic insecticide that is extensively used for controlling mosquitoes, flies, pests, and insects worldwide. This study was carried out to evaluate the likelihood protective effects of rutin, a natural antioxidant, against deltamethrin-induced liver and kidney toxicities in rats. Hepatotoxicity and nephrotoxicity were evaluated after the rats were treated orally with deltamethrin (1.28 mg/kg b.w.) alone or with rutin (25 and 50 mg/kg b.w.) for 30 days. Deltamethrin administration caused an increase in lipid peroxidation level and a decrease in activities of SOD, CAT, GPx, and GSH levels in the both tissues. Deltamethrin also increased serum ALT, AST, ALP, urea, and creatinine levels, while reduced nephrine levels in rats. In addition, deltamethrin increased the activation of inflammatory and apoptotic pathways by decreasing Bcl-2 and increasing TNF-α, NF-κB, IL-1β, p38α MAPK, COX-2, iNOS, beclin-1, Bax, and caspase-3 protein levels and/or activities. Furthermore, deltamethrin increased mRNA expression levels of PARP-1, VEGF, and immunohistochemical expressions of c-fos in the tissues. Rutin treatment significantly improved all examined parameters and restored the liver and kidney histopathological and immunohistochemical alterations. These findings demonstrate that rutin could be used to ameliorate hepatotoxicity and nephrotoxicity associated with oxidative stress, inflammation, and apoptosis in deltamethrin-induced rats.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

Bax:

Bcl-2-associated x protein

Bcl-2:

B-cell lymphoma-2

Caspase-3:

Cysteine aspartate specific protease-3

CAT:

Catalase

COX-2:

Cyclooxygenase-2

ELISA:

Enzyme-linked immunosorbent assay

GPx:

Glutathione peroxidase

GSH:

Glutathione

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

iNOS:

Inducible nitric oxide synthase

MDA:

Malondialdehyde

NF-κB:

Nuclear factor kappa B

PARP-1:

Poly[ADP-ribose]polymerase 1

p38α MAPK:

p38α mitogen-activated protein kinase

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TNF-α:

Tumor necrosis factor-α

VEGF:

Vascular endothelial growth factor

References

  • Abdallah FB, Slima AB, Dammak I, Keskes-Ammar L, Mallek Z (2010) Comparative effects of dimethoate and deltamethrin on reproductive system in male mice. Andrologia 42:182–186

    Article  Google Scholar 

  • Abdel-Daim MM, El-Ghoneimy A (2015) Synergistic protective effects of ceftriaxone and ascorbic acid against subacute deltamethrin-induced nephrotoxicity in rats. Ren Fail 37:297–304

    Article  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

    Article  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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Abdelkhalek NK, Ghazy EW, Abdel-Daim MM (2015) Pharmacodynamic interaction of Spirulina platensis and deltamethrin in freshwater fish Nile tilapia, Oreochromis niloticus: impact on lipid peroxidation and oxidative stress. Environ Sci Pollut Res 22:3023–3031

    Article  CAS  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

    Article  CAS  Google Scholar 

  • Aebi H (1984) Catalase in vitro. Method Enzymol 105:121–126

  • Ahmadvand H, Ghabaee DNZ, Malekshah AK, Navazesh A (2016) Virgin olive oil ameliorates deltamethrin-induced nephrotoxicity in mice: a biochemical and immunohistochemical assessment. Toxicol Rep 3:584–590

    Article  Google Scholar 

  • Ahmed MM, Ibrahim Laila IM (2018) Rutin ameliorates acrylamide-induced hepatotoxicity and biochemical disturbance in male albino rats. SJO6U 4:8–13

  • Ansar S, Hamed S, AlGhosoon H, AlSaedan R, Iqbal M (2016) The protective effect of rutin against renal toxicity induced by lead acetate. Toxin Rev 35:58–62

    Article  CAS  Google Scholar 

  • Arora D, Siddiqui MH, Sharma PK, Shukla Y (2016) Deltamethrin induced RIPK3-mediated caspase-independent non-apoptotic cell death in rat primary hepatocytes. Biochem Biophys Res Commun 479:217–223

    Article  CAS  Google Scholar 

  • Atakan A, Arikan H, Macunluoglu B, Tuglular S, Ulfer G, Cakalagaoglu F, Ozener C, Akoglu E (2008) Renal protective effects of leukotrienereceptor blockers in an experimental model of cyclosporine nephrotoxicity. Transplant Proc 40:279–284

  • Barlow S, Sullivan F, Lines J (2001) Risk assessment of the use of deltamethrin on bednets for the prevention of malaria. Food Chem Toxicol 39:407–422

    Article  CAS  Google Scholar 

  • Caglayan C, Kandemir FM, Darendelioğlu E, Yıldırım S, Kucukler S, Dortbudak MB (2019a) Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. J Trace Elem Med Biol 56:60–68

    Article  CAS  Google Scholar 

  • Caglayan C, Kandemir FM, Yildirim S, Kucukler S, Eser G (2019b) Rutin protects mercuric chloride-induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats. J Trace Elem Med Biol 54:69–78

    Article  CAS  Google Scholar 

  • Caglayan C, Taslimi P, Türk C, Kandemir FM, Demir Y, Gulcin İ (2019c) Purification and characterization of the carbonic anhydrase enzyme from horse mackerel (Trachurus trachurus) muscle and the impact of some metal ions and pesticides on enzyme activity. Comp Biochem Physiol Part - C: Toxicol Pharmacol 226:108605

  • Caglayan C, Taslimi P, Türk C, Gulcin İ, Kandemir FM, Demir Y, Beydemir Ş (2020) Inhibition effects of some pesticides and heavy metals on carbonic anhydrase enzyme activity purified from horse mackerel (Trachurus trachurus) gill tissues. Environ Sci Pollut Res Int 27(10):10607–10616

    Article  CAS  Google Scholar 

  • Çelik H, Kandemir FM, Caglayan C, Özdemir S, Çomaklı S, Kucukler S, Yardım A (2020) Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions. Mol Biol Rep 47:2023–2034

    Article  Google Scholar 

  • Chaitanya GV, Alexander JS, Babu PP (2010) PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal 8:31

  • Coyle JP, Mayo-Perez A, Bourgeois M, Johnson G, Morris S, Harbison R (2015) The assessment of an in-vitro model for evaluating the role of PARP in ethanol-mediated hepatotoxicity. Int J Crit Illn Inj Sci 5:9

  • Das PC, Streit TM, Cao Y, Rose RL, Cherrington N, Ross MK, Wallace AD, Hodgson E (2007) Pyrethroids: cytotoxicity and induction of CYP isoforms human hepatocytes. Drug Met Drug Interact 23:211

  • Ding Y, White CA, Muralidhara S, Bruckner JV, Bartlett MG (2004) Determination of deltamethrin and its metabolite 3-phenoxybenzoic acid in male rat plasma by high-performance liquid chromatography. J Chromatogr B 810:221–227

    Article  CAS  Google Scholar 

  • El Golli-Bennour E, Timoumi R, Annaibi E, Mokni M, Omezzine A, Bacha H, Abid-Essefi S (2019) Protective effects of kefir against deltamethrin-induced hepatotoxicity in rats. Environ Sci Pollut Res 26:18856–18865

    Article  Google Scholar 

  • Elsawy H, Badr GM, Sedky A, Abdallah BM, Alzahrani AM, Abdel-Moneim AM (2019) Rutin ameliorates carbon tetrachloride (CCl4)-induced hepatorenal toxicity and hypogonadism in male rats. PeerJ 7:e7011

    Article  Google Scholar 

  • Ferrara N (1999) Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int 56:794–814

    Article  CAS  Google Scholar 

  • Gülçin İ (2012) Antioxidant activity of food constituents: an overview. Arch Toxicol 86:345–391

    Article  Google Scholar 

  • Gulcin İ (2020) Antioxidants and antioxidant methods: an updated overview. Arch Toxicol 94:651–715

    Article  CAS  Google Scholar 

  • Hafez MM, Al-Harbi NO, Al-Hoshani AR, Al-Hosaini KA, Al Shrari SD, Al Rejaie SS, Sayed-Ahmed MM, Al-Shabanah OA (2015) Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl 4-induced hepatotoxicity in rats. Biol Res 48:30

    Article  Google Scholar 

  • Hegedűs C, Virág L (2014) Inputs and outputs of poly (ADP-ribosyl) ation: relevance to oxidative stress. Redox Biol 2:978–982

    Article  Google Scholar 

  • Hossain MM, Richardson JR (2011) Mechanism of pyrethroid pesticide–induced apoptosis: role of calpain and the ER stress pathway. Toxicol Sci 122:512–525

    Article  CAS  Google Scholar 

  • Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N (2016) Oxidative stress and inflammation: what polyphenols can do for us? Oxidative Med Cell Longev 2016:1–9

    Article  Google Scholar 

  • Jeong JJ, Ha YM, Jin YC, Lee EJ, Kim JS, Kim HJ, Seo HG, Lee JH, Kang SS, Kim YS, Chang KC (2009) Rutin from Lonicera japonica inhibits myocardial ischemia/reperfusion-induced apoptosis in vivo and protects H9c2 cells against hydrogen peroxide-mediated injury via ERK1/2 and PI3K/Akt signals in vitro. Food Chem Toxicol 47:1569–1576

    Article  CAS  Google Scholar 

  • Kadry MO, Abdel-Megeed RM, El-Meliegy E, Abdel-Hamid A-HZ (2018) Crosstalk between GSK-3, c-Fos, NFκB and TNF-α signaling pathways play an ambitious role in Chitosan Nanoparticles Cancer Therapy. Toxicol Rep 5:723–727

    Article  CAS  Google Scholar 

  • Kandemir FM, Yildirim S, Caglayan C, Kucukler S, Eser G (2019) Protective effects of zingerone on cisplatin-induced nephrotoxicity in female rats. Environ Sci Pollut Res 26:22562–22574

    Article  CAS  Google Scholar 

  • Kandemir FM, Caglayan C, Aksu EH, Yildirim S, Kucukler S, Gur C, Eser G (2020a) Protective effect of rutin on mercuric chloride-induced reproductive damage in male rats. Andrologia 52:e13524

    Article  Google Scholar 

  • Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB (2020b) Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem Toxicol 138:111190

    Article  CAS  Google Scholar 

  • Khalatbary AR, Ghaffari E, Mohammadnegad B (2015) Protective role of oleuropein against acute deltamethrin-induced neurotoxicity in rat brain. Iran Biomed J 19:247

    Google Scholar 

  • Khan RA, Khan MR, Sahreen S (2012) Protective effects of rutin against potassium bromate induced nephrotoxicity in rats. BMC Complement Altern Med 12:204

    Article  CAS  Google Scholar 

  • Kumar A, Sharma N (2015) Comparative efficacy of piperine and curcumin in deltamethrin induced splenic apoptosis and altered immune functions. Pestic Biochem Physiol 119:16–27

    Article  CAS  Google Scholar 

  • Kumar A, Bhaskar A, Chandra S, Sasmal D, Mukhopadhyay KM, Sharma N (2015) Mechanism of deltamethrin induced immunotoxicity: Current and future perspectives. Receptor Clin Invest 2:e578

  • Kumar A, Sasmal D, Bhaskar A, Mukhopadhyay K, Thakur A, Sharma N (2016) Deltamethrin-induced oxidative stress and mitochondrial caspase-dependent signaling pathways in murine splenocytes. EnTox 31:808–819

  • Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. BBRC 71:952–958

    CAS  Google Scholar 

  • Li H, Cheng F, Wei Y, Lydy MJ, You J (2017) Global occurrence of pyrethroid insecticides in sediment and the associated toxicological effects on benthic invertebrates: an overview. J Hazard Mater 324:258–271

    Article  CAS  Google Scholar 

  • Li S, Zheng X, Zhang X, Yu H, Han B, Lv Y, Liu Y, Wang X, Zhang Z (2021) Exploring the liver fibrosis induced by deltamethrin exposure in quails and elucidating the protective mechanism of resveratrol. Ecotoxicol Environ Saf 207:111501

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Article  CAS  Google Scholar 

  • Maalej A, Mahmoudi A, Bouallagui Z, Fki I, Marrekchi R, Sayadi S (2017) Olive phenolic compounds attenuate deltamethrin-induced liver and kidney toxicity through regulating oxidative stress, inflammation and apoptosis. Food Chem Toxicol 106:455–465

    Article  CAS  Google Scholar 

  • Magby JP, Richardson JR (2015) Role of calcium and calpain in the downregulation of voltage-gated sodium channel expression by the pyrethroid pesticide deltamethrin. J Biochem Mol Toxicol 29:129–134

    Article  CAS  Google Scholar 

  • Manzoni AG, Passos DF, da Silva JL, Bernardes VM, Bremm JM, Jantsch MH, de Oliveira JS, Mann TR, de Andrade CM, Leal DB (2019) Rutin and curcumin reduce inflammation, triglyceride levels and ADA activity in serum and immune cells in a model of hyperlipidemia. Blood Cells Mol Dis 76:13–21

    Article  CAS  Google Scholar 

  • Mirfazaelian A, Kim K-B, Anand SS, Kim HJ, Tornero-Velez R, Bruckner JV, Fisher JW (2006) Development of a physiologically based pharmacokinetic model for deltamethrin in the adult male Sprague-Dawley rat. Toxicol Sci 93:432–442

    Article  CAS  Google Scholar 

  • Morgan MK, MacMillan DK, Zehr D, Sobus JR (2018) Pyrethroid insecticides and their environmental degradates in repeated duplicate-diet solid food samples of 50 adults. J Expo Sci Environ Epidemiol 28:40–45

    Article  CAS  Google Scholar 

  • Nafees S, Rashid S, Ali N, Hasan SK, Sultana S (2015) Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NFκB/MAPK pathway. Chem Biol Interact 231:98–107

    Article  CAS  Google Scholar 

  • Özdemir S, Çomaklı S (2018) Investigation of the interaction between bta-miR-222 and the estrogen receptor alpha gene in the bovine ovarium. Reprod Biol 18:259–266

    Article  Google Scholar 

  • Papastefanou VP, Bozas E, Mykoniatis MG, Grypioti A, Garyfallidis S, Bartsocas CS, Nicolopoulou-Stamati P (2007) VEGF isoforms and receptors expression throughout acute acetaminophen-induced liver injury and regeneration. Arch Toxicol 81:729–741

    Article  CAS  Google Scholar 

  • Park YS, Park JH, Ko J, Shin IC, Koh HC (2017) m TOR inhibition by rapamycin protects against deltamethrin-induced apoptosis in PC 12 Cells. EnTox 32:109–121

    CAS  Google Scholar 

  • Placer ZA, Cushman LL, Johnson BC (1966) Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. AnBio 16:359–364

    CAS  Google Scholar 

  • Ray N, Kuwahara M, Takada Y, Maruyama K, Kawaguchi T, Tsubone H, Ishikawa H, Matsuo K (2006) c-Fos suppresses systemic inflammatory response to endotoxin. Int Immunol 18:671–677

    Article  CAS  Google Scholar 

  • Rjeibi I, Saad AB, Hfaiedh N (2016) Oxidative damage and hepatotoxicity associated with deltamethrin in rats: the protective effects of Amaranthus spinosus seed extract. Biomed Pharmacother 84:853–860

    Article  CAS  Google Scholar 

  • Ruzo LO, Unai T, Casida JE (1978) Decamethrin metabolism in rats. J Agric Food Chem 26:918–925

    Article  CAS  Google Scholar 

  • Sadeghnia HR, Yousefsani BS, Rashidfar M, Boroushaki MT, Asadpour E, Ghorbani A (2013) Protective effect of rutin on hexachlorobutadiene-induced nephrotoxicity. Ren Fail 35:1151–1155

    Article  CAS  Google Scholar 

  • Sayeed I, Parvez S, Pandey S, Bin-Hafeez B, Haque R, Raisuddin S (2003) Oxidative stress biomarkers of exposure to deltamethrin in freshwater fish, Channa punctatus Bloch. Ecotoxicol Environ Saf 56:295–301

    Article  CAS  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. AnBio 25:192–205

    CAS  Google Scholar 

  • Shihab FS, Bennett WM, Isaac J, Yi H, Andoh TF (2003) Nitric oxide modulates vascular endothelial growth factor and receptors in chronic cyclosporine nephrotoxicity. Kidney Int 63:522–533

    Article  CAS  Google Scholar 

  • Stanisavljević A, Perić I, Gass P, Inta D, Lang UE, Borgwardt S, Filipović D (2019) Brain sub/region-specific effects of olanzapine on c-Fos expression of chronically socially isolated rats. Neuroscience 396:46–65

    Article  Google Scholar 

  • Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    Article  CAS  Google Scholar 

  • Temel Y, Kucukler S, Yıldırım S, Caglayan C, Kandemir FM (2020) Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. Naunyn Schmiedeberg's Arch Pharmacol 393:325–337

    Article  CAS  Google Scholar 

  • Virag L (2005) Structure and function of poly (ADP-ribose) polymerase-1: role in oxidative stress-related pathologies. Curr Vasc Pharmacol 3:209–214

    Article  CAS  Google Scholar 

  • Wu A, Ren T, Hu Q, Liu Y (2000) Deltamethrin induces altered expression of P53, Bax and Bcl-2 in rat brain. Neurosci Lett 284:29–32

    Article  CAS  Google Scholar 

  • Yang J, Yan J, Liu B (2018) Targeting VEGF/VEGFR to modulate antitumor immunity. Front Immunol 9:978

    Article  Google Scholar 

  • Yousef MI, Awad TI, Mohamed EH (2006) Deltamethrin-induced oxidative damage and biochemical alterations in rat and its attenuation by vitamin E. Toxicology 227:240–247

    Article  CAS  Google Scholar 

  • Yu H-m, Wu Y, Ju P, Wang B-h, Yang X-d, Wang H-m, Xu L-c (2014) eNOS-JNK1-AR signaling pathway mediates deltamethrin-induced germ cells apoptosis in testes of adult rats. Environ Toxicol Pharmacol 38:733–741

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

    Sefa Küçükler & Fatih Mehmet Kandemir

  2. Department of Genetics, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

    Selçuk Özdemir

  3. Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

    Selim Çomaklı

  4. Department of Biochemistry, Faculty of Veterinary Medicine, Bingöl University, 12000, Bingöl, Turkey

    Cuneyt Caglayan

Authors
  1. Sefa Küçükler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatih Mehmet Kandemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Selçuk Özdemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Selim Çomaklı
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cuneyt Caglayan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SK: investigation, methodology. FMK: investigation, data curation, review and editing, supervision, SÖ: methodology, software, formal analysis. SÇ: methodology, formal analysis. CC: investigation, writing (review and editing), supervision.

Corresponding authors

Correspondence to Fatih Mehmet Kandemir or Cuneyt Caglayan.

Ethics declarations

Ethics approval

The animal care and use procedures applied in the study were conducted under the protocols approved by the Animal Experiments Local Ethics Committee of the Atatürk University (approval no: 2020-4/65).

Conflict of interest

The authors declare no competing interests.

Additional information

Responsible Editor: Mohamed M. Abdel-Daim

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Küçükler, S., Kandemir, F.M., Özdemir, S. et al. Protective effects of rutin against deltamethrin-induced hepatotoxicity and nephrotoxicity in rats via regulation of oxidative stress, inflammation, and apoptosis. Environ Sci Pollut Res 28, 62975–62990 (2021). https://doi.org/10.1007/s11356-021-15190-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-021-15190-w

Keywords

Search

Navigation