Skip to main content
Log in

Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats

  • Original Article
  • Published:
Toxicological Research Aims and scope Submit manuscript

Abstract

This study aims at investigating the protective effects of flavonoid fractions of diosmin and hesperidin in mitigating sub-chronic lead acetate-induced biochemical, oxidative stress, and histopathological alterations in adult male Wistar rats. Forty animals were randomly assigned into five groups, each consisting of eight animals. Group I animals was treated with deionised water only, group II, IV, and V were administered lead acetate 90 mg/Kg body weight (1/20th of the LD50), groups III, and IV was administered Daflon (100 mg/Kg), while group V was administered Daflon (200 mg/Kg), 30 min prior treatment with lead acetate. All treatments lasted for 42 days. Blood lead levels, electrolyte parameters, zinc protoporphyrin (ZPP) levels, activities of antioxidant enzymes, and histopathology of vital organs, were evaluated following standard practice. Sub-chronic lead acetate exposure induced a decrease in levels of serum electrolytes, and activities of antioxidant enzymes, while blood lead levels, ZPP, and malondialdehyde levels were increased. Lead exposure also instigated marked variation in histopathology of vital organs. Conversely, co-treatment with graded doses of daflon improved the levels of blood lead, electrolytes, ZPP, activities of antioxidant enzymes, and histopathology of vital organs. Data obtained from the current study indicate that rats exposed to sub-chronic doses of lead acetate show increased blood lead levels, electrolyte imbalance, alongside impairment in ZPP levels, activities of antioxidant enzymes, and histopathology, while pretreatment using daflon mitigated the ensued perturbations. This, therefore, suggests that consumption of foods enriched with flavonoid fractions of diosmin and hesperidin may be beneficial for individuals inhabiting lead-polluted environments.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Burki T (2020) Report says 815 million children have high blood lead levels. Lancet 396:370. https://doi.org/10.1016/S0140-6736(20)31684-6

    Article  Google Scholar 

  2. Hedayati A, Darabitabar F (2017) Lethal and sub-lethal impacts of lead on some hematological, biochemical and immunological indices in Caspian roach. Pollution 3:21–27. https://doi.org/10.22059/poll.2017.59567

    Article  CAS  Google Scholar 

  3. Bah H, Bandeira MJ, Gomes-Junior EA, Anjos A, Rodrigues Y, Dos Santos NR, Martinez VO, Rocha R, Costa RG, Adorno EV, Menezes-Filho JA (2020) Environmental exposure to lead and hematological parameters in Afro-Brazilian children living near artisanal glazed pottery workshops. J Environ Sci Health 55:964–974. https://doi.org/10.1080/10934529.2020.1761738

    Article  CAS  Google Scholar 

  4. Ayla O, Metin O (2015) Biochemistry of reactive oxygen and nitrogen species. Faculty of Veterinary Medicine, University of Kafkas, Turkey, Croatia, InTech, pp 37–58. https://doi.org/10.5772/61193

  5. Yabe J, Nakayama SM, Nakata H, Toyomaki H, Yohannes YB, Muzandu K, Kataba A, Zyambo G, Hiwatari M, Narita D, Yamada D, Hangoma P, Munyinda NS, Mufune T, Ikenaka Y, Choongo K, Ishizuka M (2020) Current trends of blood lead levels, distribution patterns and exposure variations among household members in Kabwe, Zambia. Chemosphere 243:125412. https://doi.org/10.1016/j.chemosphere.2019.125412

    Article  CAS  PubMed  Google Scholar 

  6. Wani AL, Ara A, Usmani JA (2015) Lead toxicity: a review. Interdiscip Toxicol 8:55–64. https://doi.org/10.1515/intox-2015-0009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Agency for Toxic Substances and Disease Registry (ATSDR) (2020) Toxicological profile for Lead. U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA. https://doi.org/10.15620/cdc:95222

  8. Ameh MP, Mohammed M, Ofemile YP, Mohammed MG, Gabriel A, Isaac AO (2020) Detoxifying Action of Aqueous Extracts of Mucuna pruriens Seed and Mimosa pudica Root Against Venoms of Naja nigricollis and Bitis arietans. Recent Pat Biotechnol 14:134–144. https://doi.org/10.2174/1872208313666191025110019

    Article  CAS  PubMed  Google Scholar 

  9. Isaac AO, Joseph AO, Victor SO, Lamidi YI, Andrew AM (2017) Ameliorative effects of kaempferol and zinc gluconate on erythrocyte osmotic fragility and haematological parameters in Wistar rats exposed to noise stress. Insights Biomed 2:15. https://doi.org/10.21767/2572-5610.100031

    Article  Google Scholar 

  10. Bokara KK, Brown E, McCormick R, Yallapragada PR, Rajanna S, Bettaiya R (2008) Lead-induced increase in antioxidant enzyme and lipid peroxidation products in developing rat brain. Biometals 21:9–16. https://doi.org/10.1007/s10534-007-9088-5

    Article  CAS  PubMed  Google Scholar 

  11. Wei W, Wu X, Bai Y, Li G, Feng Y, Meng H, Li H, Li M, Zhang X, He M, Guo H (2020) Lead exposure and its interactions with oxidative stress polymorphisms on lung function impairment: results from a longitudinal population-based study. Environ Res 187:109645. https://doi.org/10.1016/j.envres.2020.109645

    Article  CAS  PubMed  Google Scholar 

  12. Gems D, Patridge L (2008) Stress-response hormesis and aging: that which does not kill us makes us stronger. Cell Metab 7:200–203. https://doi.org/10.1016/j.cmet.2008.01.001

    Article  CAS  PubMed  Google Scholar 

  13. Isaac A, Ibrahim Y, Andrew A, Edward D, Solomon A (2017) The cortisol steroid levels as a determinant of health status in animals. J Proteomics Bioinform 10:277–283. https://doi.org/10.4172/jpb.1000452

    Article  Google Scholar 

  14. Adinortey MB, Sarfo JK, Kwarteng J, Adinortey CA, Ekloh W, Kuatsienu LE, Kwadwo Nyarko A (2018) The Ethnopharmacological and Nutraceutical Relevance of Launaea taraxacifolia (Willd.) Amin ex C. Jeffrey. Evid Based Complement Alternat Med 2018:7259146. https://doi.org/10.1155/2018/7259146

    Article  PubMed  PubMed Central  Google Scholar 

  15. Akefe IO, Ayo JO, Sinkalu VO (2020) Kaempferol and zinc gluconate mitigate neurobehavioral deficits and oxidative stress induced by noise exposure in Wistar rats. PLoS ONE 15:e0236251. https://doi.org/10.1371/journal.pone.0236251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Brodowska MK (2017) Natural flavonoids: classification, potential role, and application of flavonoid analogues. Eur J Biol Res 7:108–123. https://doi.org/10.5281/zenodo.545778

    Article  CAS  Google Scholar 

  17. Shubina VS, Shatalin YV (2017) Antioxidant and iron-chelating properties of taxifolin and its condensation product with glyoxylic acid. J Food Sci Technol 54:1467–1475. https://doi.org/10.1007/s13197-017-2573-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ramlet AA (2001) Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency. Angiology 52:49–56. https://doi.org/10.1177/000331970105200107

    Article  Google Scholar 

  19. Rizk SM, Sabri NA (2009) Evaluation of clinical activity and safety of Daflon 500 mg in type 2 diabetic female patients. Saudi Pharm J 17:199–207. https://doi.org/10.1016/j.jsps.2009.08.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Prabhu VV, Sathyamurthy D, Ramasamy A, Das S, Anuradha M, Pachiappan S (2016) Evaluation of protective effects of diosmin (a citrus flavonoid) in chemical-induced urolithiasis in experimental rats. Pharm Biol 54:1513–1521. https://doi.org/10.3109/13880209.2015.1107105

    Article  CAS  PubMed  Google Scholar 

  21. Lamidi IY, Hudu MG, Akefe IO, Adamu S, Salihu SI (2020) Sub-chronic administration of flavonoid fraction Daflon improve lead-induced alterations in delta-aminolevulinic acid dehydratase activity, erythrocytic parameters, and erythrocyte osmotic fragility in Wistar rats. Comp Clin Pathol. https://doi.org/10.1007/s00580-020-03144-6

    Article  Google Scholar 

  22. Eman G, Fawzi B (2020) Micronized flavonoid fraction Daflon 500 protects heart against ischemia–reperfusion injury: an old medicine for a new target. All Life 13:556-568. https://doi.org/10.1080/26895293.2020.1832921

    Article  CAS  Google Scholar 

  23. Lamidi IY, Akefe IO (2017) Mitigate effects of antioxidants in lead toxicity. Clin Pharmacol Toxicol J 1:1–9

    Google Scholar 

  24. Garber JC, Barbee RW, Bielitzki JT, Clayton LA, Donovan JC, Kohn DF, Lipman NS et al (2011) Guide for the care and use of laboratory animals, 8th edn. National Academies Press, Washington, DC

    Google Scholar 

  25. Kobo PI, Ayo JO, Aluwong T, Zezi AU, Maikai V, Ambali SF (2014) Flavonoid mixture ameliorates increase in erythrocyte osmotic fragility and malondialdehyde concentration induced by Trypanosoma brucei brucei-infection in Wistar rats. Res Vet Sci 96:139–142. https://doi.org/10.1016/j.rvsc.2013.10.005

    Article  CAS  PubMed  Google Scholar 

  26. Erick H, Yong W, Ian DB (2016) A novel methodology for rapid digestion of rare earth element ores and determination by microwave plasma-atomic emission spectrometry and dynamic reaction cell-inductively coupled plasma-mass spectrometry. Talanta 160:521–527. https://doi.org/10.1016/j.talanta.2016.07.067

    Article  CAS  Google Scholar 

  27. Grandjean P (1979) Occupational lead exposure in Denmark: screening with a haematofluorimeter. Br J Ind Med 36:52–58. https://doi.org/10.1136/oem.36.1.52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Martin JP Jr, Dailey M, Sugarman E (1987) Negative and positive assays of superoxide dismutase based on haematoxylin autoxidation. Arch Biochem Biophys 225:329–336. https://doi.org/10.1016/0003-9861(87)90400-0

    Article  Google Scholar 

  29. Palgia DE, Valentine WN (1967) Studies on qualitative and quantitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    Google Scholar 

  30. Beers FN, Sizer IW (1952) A spectrophotometric method for measuring the break-down of hydrogen peroxide by catalase. J Biol Chem 195:133–140

    Article  CAS  Google Scholar 

  31. 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

    Article  CAS  PubMed  Google Scholar 

  32. Altuntas I, Delibas N, Sutcu R (2002) The effects of organophosphate insecticide methidathion on lipid peroxidation and anti-oxidant enzymes in rat erythrocytes: role of vitamins E and C. Hum Exp Toxicol 21:681–685. https://doi.org/10.1191/0960327102ht304oa

    Article  CAS  PubMed  Google Scholar 

  33. Luna GH (1960) Manual of histologic staining method of armed forces institute of pathology, 35th edn. McGraw-Hill Book Company, New York, p 46

    Google Scholar 

  34. Akefe IO, Yusuf IL, Adegoke VA (2019) C-glycosyl flavonoid orientin alleviates learning and memory impairment by radiofrequency electromagnetic radiation in mice via improving antioxidant defence mechanism. Asian Pac J Trop Biomed 9:518-523. https://doi.org/10.4103/2221-1691.271725

  35. Suradkar SG, Ghodasara DJ, Vihol P, Patel J, Jaiswal V, Prajapati KS (2009) Haematobiochemical alterations induced by lead acetate toxicity in wistar rats. Vet World 2:429–439

    Google Scholar 

  36. Sakai T (2000) Biomarkers of lead exposure. Ind Health 38:127–142. https://doi.org/10.2486/indhealth.38.127

    Article  CAS  PubMed  Google Scholar 

  37. Rendon-Ramirez A, Cerbon-Solorzano J, Maldonado-Vega M, Quintanar-Escorza MA, Calderon-Salinas JV (2007) Vitamin E reduces the oxidative damage on d-aminolevulinic dehydratase induced by lead intoxication in rat erythrocytes. Toxicol In Vitro 21:1121–1126. https://doi.org/10.1016/j.tiv.2007.04.019

    Article  CAS  PubMed  Google Scholar 

  38. Eze JI, Anene BM, Chukwu CC (2008) Determination of serum and organ malondialdehyde (MDA) concentration, a lipid peroxidation index in Trypanosoma bruceiinfected rats. Comp Clin Pathol 17:67–72. https://doi.org/10.1007/s00580-008-0722-6

    Article  CAS  Google Scholar 

  39. Aksu DS, Didin M, Kayikci F (2012) The protective role of polyphenols on blood cells in rats exposed to lead. Rev Română Med Lab 20:233–243

    Google Scholar 

  40. Nisar NA, Sultana M, Waiz HA, Para PA, Baba NA, Zargar FA, Raja WH (2013) Experimental study on the effect of vitamin C administration on lipid peroxidation and antioxidant enzyme activity in rats exposed to chlorpyriphos and lead acetate. Vet World 6:461–466. https://doi.org/10.5455/vetworld.2013.461-466

    Article  CAS  Google Scholar 

  41. Wang J, Zhu H, Yang Z, Liu Z (2013) Antioxidative effects of hesperetin against lead acetate-induced oxidative stress in rats. Indian J Toxicol 45:395–398. https://doi.org/10.4103/0253-7613.115015

    Article  CAS  Google Scholar 

  42. Okediran BS, Biobaku KT, Olaifa FH, Atata AJ (2017) Haematological and antioxidant enzyme response to lead toxicity in male Wistar rats. Ceylon J Sci 46:31–37. https://doi.org/10.4038/cjs.v46i2.7427

    Article  Google Scholar 

  43. Jalali MS, Seyedeh NH, Mousavi M (2017) Comparative effect of silymarin and D-penicillamine on lead induced hemotoxicity and oxidative stress in rat. Iranian J Toxicol 11:12–18. https://doi.org/10.29252/arakmu.11.3.11

    Article  Google Scholar 

  44. Ujowundu CO, Okwu GN, Achilike JJ, Nwaogu LA, Iheme CI (2017) Lead-induced oxidative stress and chemoprotective role of dietary supplements on Wistar albino rats. Annu Res Rev Biol 13:1–14. https://doi.org/10.9734/ARRB/2017/33167

    Article  Google Scholar 

  45. Gurer H, Ozgunes H, Neal R, Spitzand DR, Ercal N (1998) Antioxidant effects of N–acetyl cysteine and succimer in red blood cells from lead-exposed rats. Toxicology 128:181–189. https://doi.org/10.1016/j.tox.2004.07.006

    Article  CAS  PubMed  Google Scholar 

  46. Shalana M, Mostafab M, Hassounab M (2005) Amelioration of lead toxicity on rat liver with vitamin and silymarin supplements. Toxicology 206:1–15. https://doi.org/10.1016/j.tox.2004.07.006

    Article  CAS  Google Scholar 

  47. Patra RCD, Swarup SK, Dwivedi AS (2001) Trace minerals in blood of young calves during exposure to lead. Indian J Animal Sci 71:507–510. https://doi.org/10.4061/2011/457327

    Article  CAS  Google Scholar 

  48. Patra RC, Rautray AK, Swarup D (2011) Oxidative stress in lead and cadmium toxicity and its amelioration. Vet Med Int 22:1–9. https://doi.org/10.4061/2011/457327

    Article  Google Scholar 

  49. Flora SJ, Flora G, Saxena G, Mishra M (2007) Arsenic and lead induced free radical generation and their reversibility following chelation. Cell Mol Biol 53:26–47. https://doi.org/10.1170/T773

    Article  CAS  PubMed  Google Scholar 

  50. Sidhu P, Nehru B (2004) Lead intoxication: histological and oxidative damage in rat cerebrum and cerebellum. J Trace Elements Exp Med 17:45–53. https://doi.org/10.1002/jtra.10052

    Article  CAS  Google Scholar 

  51. Kayode IMO, Olugbenga IE (2017) Lead acetate induced cerebral tissue damage; The effect of Phoenix dactylifera pits extract. Eur J Med Plants 21:1–9. https://doi.org/10.9734/EJMP/2017/37302

    Article  Google Scholar 

  52. Lawton LJ, Donaldson WE (1991) Lead-induced tissue fatty acid alterations and lipid peroxidation. Biol Trace Elem Res 28:83–97. https://doi.org/10.1007/BF02863075

    Article  CAS  PubMed  Google Scholar 

  53. Julka D, Pal R, Gill KD (1992) Neurotoxicity of dichlorvos: effect on antioxidant system in the rat central nervous system. Exp Mol Pathol 56:144–152. https://doi.org/10.1016/0014-4800(92)90031-6

    Article  CAS  PubMed  Google Scholar 

  54. Gajawat S, Sancheti G, Goyal P (2005) Vitamin C against concomitant exposure to heavy metal and radiation: a study on variations in hepatic cellular counts. Asian J Exposure Sci 19:53–58. https://doi.org/10.1007/s12291-013-0375-3

    Article  CAS  Google Scholar 

  55. Johar D, Roth JC, Bay GH, Walker JN, Kroczak TJ, Los M (2004) Inflammatory response, reactive oxygen species, programmed (necrotic-like and apoptotic) cell death and cancer. Roczniki Akademia Medyczna Bialymstoku 49:31–39

    CAS  Google Scholar 

  56. Ozkaya A, Sahin Z, Kuzu M, Selim Y, Mustafa S, Mirac O, Ertan U, Veysel Y, Ramazan C, Yologlu S (2017) Role of geraniol against lead acetate-mediated hepatic damage and their interaction with liver carboxylesterase activity in rats. Arch Physiol Biochem 17:1–8. https://doi.org/10.1080/13813455.2017.1364772

    Article  CAS  Google Scholar 

  57. Yasim A, Ozbag D, Kilinc M, Ciralik H, Toru I (2011) The effects of diosmin-hesperidin combination treatment on the lipid profile and oxidative antioxidative systems in high-cholesterol diet-fed rats. Turkey Gorgus Kalp Damar Cerrahisi Dergisi 1:55–61. https://doi.org/10.5897/IJMMS.9000121

    Article  Google Scholar 

Download references

Acknowledgement

Authors are grateful to Mr. Denis Otie and Abdulwahab Hashimu of Veterinary Pharmacology and Toxicology Laboratory, Ahmadu Bello University Zaria for their technical inputs in the accomplishment of this project.

Funding

No external fund was received for this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Isaac Oluwatobi Akefe.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lamidi, I.Y., Mikail, H.G., Adamu, S. et al. Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats. Toxicol Res. 37, 473–484 (2021). https://doi.org/10.1007/s43188-020-00084-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43188-020-00084-9

Keywords

Navigation