1. bookVolume 6 (2022): Issue 1 (January 2022)
Journal Details
First Published
30 Jan 2017
Publication timeframe
4 times per year
access type Open Access

Chemical toxicity assessment and Physiological investigation in rats exposed to pyrethroid insecticide type 1 and possible mitigation of propolis

Published Online: 24 Jan 2022
Page range: 9 - 26
Journal Details
First Published
30 Jan 2017
Publication timeframe
4 times per year

The current investigation aims to study the potential protective effects of propolis methanolic extract (100 mg/kg BW) on the systemic toxic effects after dietary exposure concentration (1/100 LD50 for 30 days) of permethrin (PM) administered in experimental rats. In this experiment, we added propolis four weeks after PM -administration to examining the medicinal effects. Therapeutic use of propolis mitigated PM -induced deterioration of liver and kidney functions and myocardial damage measured by cardiac enzymes lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) in serum. In addition, propolis treatment (prophylactic and therapeutic) prevented PM-induced apoptosis index, including B-cell lymphoma protein 2 (BCL-2)-associated X (BAX) protein activates, and lipid peroxide (LP). The results showed propolis induced a significant decrease in serum levels of thyroid hormones (T3 and T4), proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), interleukin one beta (IL-1β), interleukin 12 (IL-12), and interleukin 6 (IL-6). Besides, nuclear factor-kappa B (NF-kB), acetylcholine esterase (AChE), and hematological constituents. Cardiac biomarkers, liver, and kidney functions were substantially lower in propolis treatment. High-performance liquid chromatography (HPLC) and Gas chromatography–mass spectrometry (GC- MS) of the propolis-MeOH extract showed valuable antioxidant phenolics and flavonoids capable of alleviating oxidative stress through the free-radical scavenging efficacy and regulating signaling pathways of proinflammatory cytokines.


1. Saleh HM, Mahmoud HH, Abdou MI, Eskander SB. Health risk assessment based on metal analysis of soil and crops in Al-Dakhla Oasis. Arab J Geosci [Internet]. 2021;14(4):260. Available from: https://doi.org/10.1007/s12517-021-06597-310.1007/s12517-021-06597-3 Search in Google Scholar

2. Saleh HM, Moussa HR, El-Saied FA, Dawoud M, Nouh ESA, Abdel Wahed RS. Adsorption of cesium and cobalt onto dried Myriophyllum spicatum L. from radio-contaminated water: Experimental and theoretical study. Prog Nucl Energy [Internet]. 2020 Jul;125:103393. Available from: https://linkinghub.elsevier.com/retrieve/pii/S014919702030145110.1016/j.pnucene.2020.103393 Search in Google Scholar

3. Saleh HM, Mahmoud HH, Aglan RF, Bayoumi TA. Biological treatment of wastewater contaminated with Cu(II), Fe(II) and Mn(II) using Ludwigia stolonifera aquatic plant. Environ Eng Manag J. 2019;18(6):1327–36.10.30638/eemj.2019.126 Search in Google Scholar

4. Dawoud MMA, Hegazy MM, Helew WK, Saleh HM. Overview of Environmental Pollution and Clean Management of Heavy Metals and Radionuclides by using Microcrystalline Cellulose. J Nucl Ene Sci Power Gener Technol. 2021;3:2. Search in Google Scholar

5. Saleh HM, El-Sheikh SM, Elshereafy EE, Essa AK. Performance of cement-slag-titanate nanofibers composite immobilized radioactive waste solution through frost and flooding events. Constr Build Mater. 2019;223:221–32.10.1016/j.conbuildmat.2019.06.219 Search in Google Scholar

6. Saleh HM, Eskander SB. Impact of water flooding on hard cement-recycled polystyrene composite immobilizing radioactive sulfate waste simulate. Constr Build Mater. 2019;222:522–30.10.1016/j.conbuildmat.2019.06.173 Search in Google Scholar

7. Saleh HM, Aglan RF, Mahmoud HH. Qualification of corroborated real phytoremediated radioactive wastes under leaching and other weathering parameters. Prog Nucl Energy [Internet]. 2020 Jan;119:103178. Available from: https://linkinghub.elsevier.com/retrieve/pii/S014919701930287210.1016/j.pnucene.2019.103178 Search in Google Scholar

8. Alphey L, Benedict M, Bellini R, Clark GG, Dame DA, Service MW, et al. Sterile-insect methods for control of mosquito-borne diseases: an analysis. Vector-Borne Zoonotic Dis. 2010;10(3):295–311.10.1089/vbz.2009.0014294617519725763 Search in Google Scholar

9. Perkins JH. Insects, experts, and the insecticide crisis: the quest for new pest management strategies. Springer Science & Business Media; 2012. Search in Google Scholar

10. Odukkathil G, Vasudevan N. Toxicity and bioremediation of pesticides in agricultural soil. Rev Environ Sci Bio/Technology. 2013;12(4):421–44.10.1007/s11157-013-9320-4 Search in Google Scholar

11. Costa CA, Guiné RPF, Costa DVTA, Correia HE, Nave A. Pest control in organic farming. In: Organic Farming. Elsevier; 2019. p. 41–90.10.1016/B978-0-12-813272-2.00003-3 Search in Google Scholar

12. Meyer DA, Carter JM, Johnstone AFM, Shafer TJ. Pyrethroid modulation of spontaneous neuronal excitability and neurotransmission in hippocampal neurons in culture. Neurotoxicology. 2008;29(2):213–25.10.1016/j.neuro.2007.11.00518243323 Search in Google Scholar

13. 13. SMITH TM, STRATTON GW. Effects of synthetic pyrethroid insecticides. Residue Rev Rev Environ Contam Toxicol. 2012;97:93. Search in Google Scholar

14. 14. Wang X, Anadón A, Wu Q, Qiao F, Ares I, Martínez-Larrañaga M-R, et al. Mechanism of neonicotinoid toxicity: impact on oxidative stress and metabolism. Annu Rev Pharmacol Toxicol. 2018;58:471–507.10.1146/annurev-pharmtox-010617-05242928968193 Search in Google Scholar

15. Yadav IC, Devi NL. Pesticides classification and its impact on human and environment. Environ Sci Eng. 2017;6:140–58. Search in Google Scholar

16. Li F-S, Weng J-K. Demystifying traditional herbal medicine with modern approach. Nat plants. 2017;3(8):1–7. Search in Google Scholar

17. Okail HA, Ibrahim AS, Badr AH. The protective effect of propolis against aluminum chloride-induced hepatorenal toxicity in albino rats. J Basic Appl Zool. 2020;81(1):1–11.10.1186/s41936-020-00169-9 Search in Google Scholar

18. Kapare HS, Sathiyanarayanan L. Nutritional and Therapeutic potential of Propolis: A Review. Res J Pharm Technol. 2020;13(7):3545.10.5958/0974-360X.2020.00627.7 Search in Google Scholar

19. Woźniak M, Mrówczyńska L, Kwaśniewska-Sip P, Waśkiewicz A, Nowak P, Ratajczak I. Effect of the solvent on propolis phenolic profile and its antifungal, antioxidant, and in vitro cytoprotective activity in human erythrocytes under oxidative stress. Molecules. 2020;25(18):4266.10.3390/molecules25184266757111632957629 Search in Google Scholar

20. Zhang J, Ding C, Zhang S, Xu Y. Neuroprotective effects of astaxanthin against oxygen and glucose deprivation damage via the PI3K/Akt/GSK3β/Nrf2 signalling pathway in vitro. J Cell Mol Med. 2020;24(16):8977–85.10.1111/jcmm.15531741772332567157 Search in Google Scholar

21. Yilmaz S, Kandemir FM, Kaya E, Ozkaraca M. Chemo-protective effects of propolis on aflatoxin b1-induced hepatotoxicity in rats: Oxidative damage and hepatotoxicity by modulating TP53, oxidative stress. Curr Proteomics. 2020;17(3):191–9.10.2174/1570164617666190925121720 Search in Google Scholar

22. Anjum SI, Ullah A, Khan KA, Attaullah M, Khan H, Ali H, et al. Composition and functional properties of propolis (bee glue): A review. Saudi J Biol Sci. 2019;26(7):1695–703.10.1016/j.sjbs.2018.08.013686420431762646 Search in Google Scholar

23. Geyikoglu F, Koc K, Colak S, Erol HS, Cerig S, Yardimci BK, et al. Propolis and its combination with boric acid protect against ischemia/reperfusion-induced acute kidney injury by inhibiting oxidative stress, inflammation, DNA damage, and apoptosis in rats. Biol Trace Elem Res. 2019;192(2):214–21.10.1007/s12011-019-1649-230783919 Search in Google Scholar

24. Reis JH de O, Barreto G de A, Cerqueira JC, Anjos JP dos, Andrade LN, Padilha FF, et al. Evaluation of the antioxidant profile and cytotoxic activity of red propolis extracts from different regions of northeastern Brazil obtained by conventional and ultrasound-assisted extraction. PLoS One. 2019;14(7):e0219063.10.1371/journal.pone.0219063661159531276476 Search in Google Scholar

25. Dantas Silva RP, Machado BAS, Barreto G de A, Costa SS, Andrade LN, Amaral RG, et al. Antioxidant, antimicrobial, antiparasitic, and cytotoxic properties of various Brazilian propolis extracts. PLoS One. 2017;12(3):e0172585.10.1371/journal.pone.0172585537351828358806 Search in Google Scholar

26. Almuhayawi MS. Propolis as a novel antibacterial agent. Saudi J Biol Sci. 2020;27(11):3079.10.1016/j.sjbs.2020.09.016 Search in Google Scholar

27. Sartori G, Pesarico AP, Pinton S, Dobrachinski F, Roman SS, Pauletto F, et al. Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti+inflammatory mechanisms. Cell Biochem Funct. 2012;30(1):1–10.10.1002/cbf.1810 Search in Google Scholar

28. dos Santos DA, Munari FM, da Silva Frozza CO, Moura S, Barcellos T, Henriques JAP, et al. Brazilian red propolis extracts: study of chemical composition by ESI-MS/MS (ESI+) and cytotoxic profiles against colon cancer cell lines. Biotechnol Res Innov. 2019;3(1):120–30.10.1016/j.biori.2019.02.001 Search in Google Scholar

29. Daikh A, Segueni N, Dogan NM, Arslan S, Mutlu D, Kivrak I, et al. Comparative study of antibiofilm, cytotoxic activity and chemical composition of Algerian propolis. J Apic Res. 2020;59(2):160–9.10.1080/00218839.2019.1701777 Search in Google Scholar

30. Touzani S, Embaslat W, Imtara H, Kmail A, Kadan S, Zaid H, et al. In vitro evaluation of the potential use of propolis as a multitarget therapeutic product: physicochemical properties, chemical composition, and immunomodulatory, antibacterial, and anticancer properties. Biomed Res Int. 2019;2019.10.1155/2019/4836378 Search in Google Scholar

31. Ripari N, Sartori AA, da Silva Honorio M, Conte FL, Tasca KI, Santiago KB, et al. Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment. J Pharm Pharmacol. 2021;73(3):281–99.10.1093/jpp/rgaa067 Search in Google Scholar

32. Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Vol. 64, Food Chemistry. 1999. p. 555–9.10.1016/S0308-8146(98)00102-2 Search in Google Scholar

33. Rodríguez-Bernaldo de Quirós A, Lage-Yusty MA, López-Hernández J. Determination of phenolic compounds in macroalgae for human consumption. Food Chem. 2010;121(2):634–8.10.1016/j.foodchem.2009.12.078 Search in Google Scholar

34. Chu Y, Chang C, Hsu H. Flavonoid content of several vegetables and their antioxidant activity. J Sci Food Agric. 2000;80(5):561–6.10.1002/(SICI)1097-0010(200004)80:5<561::AID-JSFA574>3.0.CO;2-# Search in Google Scholar

35. Arnao MB, Cano A, Acosta M. The hydrophilic and lipophilic contribution to total antioxidant activity. Food Chem. 2001;73(2):239–44.10.1016/S0308-8146(00)00324-1 Search in Google Scholar

36. Kuda T, Tsunekawa M, Goto H, Araki Y. Antioxidant properties of four edible algae harvested in the Noto Peninsula, Japan. J food Compos Anal. 2005;18(7):625–33.10.1016/j.jfca.2004.06.015 Search in Google Scholar

37. Okihashi M, Kitagawa Y, Akutsu K, Obana H, Tanaka Y. Rapid method for the determination of 180 pesticide residues in foods by gas chromatography/mass spectrometry and flame photometric detection. J Pestic Sci. 2005;30(4):368–77.10.1584/jpestics.30.368 Search in Google Scholar

38. Guideline P-BT. OECD guideline for the testing of chemicals. The Hershberger. 2001;601:858. Search in Google Scholar

39. Cantalamessa F. Acute toxicity of two pyrethroids, permethrin, and cypermethrin in neonatal and adult rats. Arch Toxicol. 1993;67(7):510–3.10.1007/BF01969923 Search in Google Scholar

40. Weichselbaum CTE. An accurate and rapid method for the determination of proteins in small amounts of blood serum and plasma. Am J Clin Pathol. 1946;16(3_ts):40–9.10.1093/ajcp/16.3_ts.40 Search in Google Scholar

41. Würzburg U, Hennrich N, Lang H, Prellwitz W, Neumeier D, Knedel M. Determination of creatine kinase-MB in serum using inhibiting antibodies (author’s transl). Klin Wochenschr. 1976;54(8):357–60.10.1007/BF01469790 Search in Google Scholar

42. Buhl SN, Jackson KY. Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30, and 37 degrees C. Clin Chem. 1978;24(5):828–31.10.1093/clinchem/24.5.828 Search in Google Scholar

43. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.10.1016/0003-2697(79)90738-3 Search in Google Scholar

44. Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996;239(1):70–6.10.1006/abio.1996.0292 Search in Google Scholar

45. Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7(2):88–95.10.1016/0006-2952(61)90145-9 Search in Google Scholar

46. Suvarna KS, Layton C, Bancroft JD. Bancroft’s theory and practice of histological techniques E-Book. Elsevier Health Sciences; 2018. Search in Google Scholar

47. Nna VU, Bakar ABA, Lazin MRMLM, Mohamed M. Antioxidant, anti-inflammatory and synergistic anti-hyper-glycemic effects of Malaysian propolis and metformin in streptozotocin–induced diabetic rats. Food Chem Toxicol. 2018;120:305–20.10.1016/j.fct.2018.07.02830026088 Search in Google Scholar

48. Nna VU, Abu Bakar AB, Ahmad A, Eleazu CO, Mohamed M. Oxidative stress, NF-κb-mediated inflammation and apoptosis in the testes of streptozotocin–induced diabetic rats: Combined protective effects of malaysian propolis and metformin. Antioxidants. 2019;8(10):465.10.3390/antiox8100465682657131600920 Search in Google Scholar

49. Askari VR, Rahimi VB, Zamani P, Fereydouni N, Rahmanian-Devin P, Sahebkar AH, et al. Evaluation of the effects of Iranian propolis on the severity of post operational-induced peritoneal adhesion in rats. Biomed Pharmacother. 2018;99:346–53.10.1016/j.biopha.2018.01.06829665643 Search in Google Scholar

50. Ramadan A, Soliman G, Mahmoud SS, Nofal SM, Abdel-Rahman RF. Evaluation of the safety and antioxidant activities of Crocus sativus and Propolis ethanolic extracts. J Saudi Chem Soc. 2012;16(1):13–21.10.1016/j.jscs.2010.10.012 Search in Google Scholar

51. Menegaux F, Baruchel A, Bertrand Y, Lescoeur B, Leverger G, Nelken B, et al. Household exposure to pesticides and risk of childhood acute leukaemia. Occup Environ Med. 2006;63(2):131–4.10.1136/oem.2005.023036207807516421392 Search in Google Scholar

52. Nebeker A V, Dunn KD, Griffis WL, Schuytema GS. Effects of dieldrin in food on growth and bioaccumulation in mallard ducklings. Arch Environ Contam Toxicol. 1994;26(1):29–32.10.1007/BF00212790 Search in Google Scholar

53. Jaffe S, Sevinsky JA. secret hazards of pesticides. 1991; Search in Google Scholar

54. Davis G, Hickox WH, Helliker PE. Summary of pesticide use report data. State California, EPA, Sacramento, CA. 1996; Search in Google Scholar

55. Achudume AC. The influence of chloroquine administration on antioxidant levels, oxidant marker and total cholesterol in Wistar rats. Biol Med. 2009;1:39–43. Search in Google Scholar

56. Ali T, Ahmed O, Ahmed R. Biochemical and Hematological Effects of Food Flavoring Furfural in Male Albino Rats. Bull Egypt Soc Physiol Sci. 2012;32(1):93–110.10.21608/besps.2012.35529 Search in Google Scholar

57. Jaitly D, PRASAD A, Singh DB. Illiteracy & India. Int J Transform Bus Manag. 2012;1(5):1–7. Search in Google Scholar

58. Paulino CA, Guerra JL, Oliveira GH de, Palermo-Neto J. Acute, subchronic and chronic 2, 4-dichlorophenoxyacetic acid (2, 4-D) intoxication in rats. Vet Hum Toxicol. 1996;38(5):348–52. Search in Google Scholar

59. Abbas NAT, Awad MM, Nafea OE. Silymarin in combination with chlorogenic acid protects against hepatotoxicity induced by doxorubicin in rats: possible role of adenosine monophosphate–activated protein kinase pathway. Toxicol Res (Camb). 2020;9(6):771–7.10.1093/toxres/tfaa080778617333447361 Search in Google Scholar

60. Mohamed F, Endre ZH, Pickering JW, Jayamanne S, Palangasinghe C, Shahmy S, et al. Mechanism-specific injury biomarkers predict nephrotoxicity early following glyphosate surfactant herbicide (GPSH) poisoning. Toxicol Lett. 2016;258:1–10.10.1016/j.toxlet.2016.06.00127288352 Search in Google Scholar

61. Stevanovic T, Diouf PN, Garcia-Perez ME. Bioactive polyphenols from healthy diets and forest biomass. Curr Nutr Food Sci. 2009;5(4):264–95.10.2174/157340109790218067 Search in Google Scholar

62. Mostafalou S, Abdollahi M. Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicol Appl Pharmacol. 2013;268(2):157–77.10.1016/j.taap.2013.01.02523402800 Search in Google Scholar

63. Shang H, Bhagavathula AS, Aldhaleei WA, Rahmani J, Karam G, Rinaldi G, et al. Effect of propolis supplementation on C-reactive protein levels and other inflammatory factors: A systematic review and meta-analysis of randomized controlled trials. J King Saud Univ. 2020;32(2):1694–701.10.1016/j.jksus.2020.01.003 Search in Google Scholar

64. Selvaraj R, Sivakumari K, Rajesh S, Ashok K. Molecular docking interaction of propolis with Caspase-3, Caspase-9, Bax, Bcl-2 And Bcl-Xl. IJRAR-International J Res Anal Rev. 2019;6(2):33–8. Search in Google Scholar

65. Fillion M, Mergler D, José C, Passos S, Larribe F, Lemire M, et al. Environmental Health : A Global A preliminary study of mercury exposure and blood pressure in the Brazilian Amazon. Blood Press. 2006;9:1–9. Search in Google Scholar

66. Chrustek A, Hołyńska-Iwan I, Dziembowska I, Bogusiewicz J, Wróblewski M, Cwynar A, et al. Current research on the safety of pyrethroids used as insecticides. Medicina (B Aires). 2018;54(4):61.10.3390/medicina54040061617433930344292 Search in Google Scholar

67. Rao GV, Rao KSJ. Inhibition of monoamine oxidase-A of rat brain by pyrethroids—anin vitro kinetic study. Mol Cell Biochem. 1993;124(2):107–14.10.1007/BF009292028232282 Search in Google Scholar

68. Nassar AMK, Salim YMM, Eid KSA, Shaheen HM, Saati AA, Hetta HF, et al. Ameliorative effects of honey, propolis, pollen, and royal jelly mixture against chronic toxicity of sumithion insecticide in white albino rats. Molecules. 2020;25(11):2633.10.3390/molecules25112633732123832517066 Search in Google Scholar

69. Council NR. Understanding risk: Informing decisions in a democratic society. National Academies Press; 1996. Search in Google Scholar

70. Touitou Y, Smolensky MH, Portaluppi F. Ethics, standards, and procedures of animal and human chronobiology research. Chronobiol Int. 2006;23(6):1083–96.10.1080/0742052060105530817190696 Search in Google Scholar

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