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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

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Abstract

This study investigated the ameliorative potential of micronized purified flavonoid fraction Daflon on lead-induced alterations in heme-biosynthetic enzyme delta-aminolevulinic acid dehydratase (δ-ALAD) activity and erythrocytic parameters. Thirty-two male adult Wistar rats were divided by simple randomization into four groups of eight rats each. Lead acetate was administered orally at a dose of 190 mg/kg (1/20th of the LD50) body weight for 42 days, either alone or with Daflon at a dose of 100 mg/kg body weight. Blood lead level (BLL) was analyzed using the microwave plasma atomic emission spectrometer (MP-AES), while δ-ALAD activity was quantified using assay kit. Erythrocyte parameters (RBC, packed cell volume, Hb, MCV, and MCHC) were assayed using an automated hematologic analyzer. Erythrocyte osmotic fragility (EOF) was also analyzed using standard procedure. Sub-chronic exposure to lead acetate caused impairment in δ-ALAD activity, erythrocytic parameters, and increased EOF. Conversely, Daflon improved the activity of δ-ALAD and erythrocytic parameters by protecting the integrity of the erythrocyte membrane. The results of our study revealed that sub-chronic exposure of rats to lead acetate induced impairment in δ-ALAD, erythrocytic parameters, and EOF, while pretreatment with Daflon alleviated the ensued changes, and therefore suggested that dietary supplementation with Daflon-enriched foods may be a promising prophylactic agent for individuals living in lead toxicity prone environments.

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References

  • Abadin H, Ashizawa A, Stevens YW, Llados F, Diamond G, Sage G, Citra M, Quinones A, Bosch SJ, Swarts SG (2007) Toxicological profile for lead; the United States Public Health Service, Agency for Toxic Substances and Disease Registry: Atlanta, GA, USA, p 582

  • Akande MG, Aliu YO, Ambali SF, Ayo JO (2014) Protective effect of taurine in chlorpyrifos and lead-induced hematological alterations in Wistar rats. Toxicol Environ Chem 96(1):171–182

    CAS  Google Scholar 

  • Alya A, Ines BD, Montassar L, Najoua GH, Saloua EF (2015) Oxidative stress, biochemical alterations and hyperlipidemia in female rats induced by lead chronic toxicity during puberty and post puberty periods. Iran J Basic Med Sci 18:1034–1043

    PubMed  PubMed Central  Google Scholar 

  • Ambali SF, Abubakar M, Shittu M, Yaqub LS, Anafi SB, Abdullahi A (2010) Chlorpyrifos-induced alteration of haematological parameters in Wistar rats: ameriolative effect of zinc. Res J Environ Toxicol 4:55–66

    CAS  Google Scholar 

  • Anakwue RC, Anakwue AC (2014) Cardiovascular disease profiling in Africa: environmental pollutants are not on the agenda. Cardiovasc Toxicol 14:193–207

    PubMed  CAS  Google Scholar 

  • Andjelkovic M, Djordjevic AB, Antonijevic E, Antonijevic B, Stanic M, Kotur-Stevuljevic J, Spasojevic-Kalimanovska V, Jovanovic M, Boricic N, Wallace D, Bulat Z (2019) Toxic effect of acute cadmium and Lead exposure in rat blood, liver, and kidney. Int J Environ Res Public Health 16:274–295

    PubMed Central  CAS  Google Scholar 

  • Andrew NN (2003) From symptoms to leg edema: efficacy of Daflon 500 mg. Angiology 54(1):33–44

    Google Scholar 

  • Asala OO, Ayo JO, Rekwot PI, Minka NS, Omoniwa DO, Adenkola AY (2011) Effect of ascorbic acid administration on erythrocyte osmotic fragility of pigs transported by road during the hot-dry season. Vet Res Commun 35:245–254

    PubMed  Google Scholar 

  • Bartrem C, Tirima S, Von Lindern I, Von Braun M, Worrell MC, Mohammed AS, Abdullahi A, Moller G (2014) Unknown risk: co-exposure to lead and other heavy metals among children living in small-scale mining communities in Zamfara state, Nigeria. Int J Environ Health Res 24:304–319

    PubMed  CAS  Google Scholar 

  • Dacie JV, Lewis SM (1991) Practical Haematology, 7th edn. Churchill Livingstone, London, p 659–661

  • Debosree G, Sudeshna P, Shamreen N, Debajit B, Mousumi D, Arnab KG, Syed BF, Aindrila C, Russel JR, Debasish B (2016) Melatonin protects against lead acetate induced oxidative stress-mediated changes in morphology and metabolic status in rat red blood cells: a flow cytometric and biochemical analysis. J Pharm Res 10(6):381–402

    Google Scholar 

  • 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

    Google Scholar 

  • Faulkner WR, King JW (1970) Manual of clinical laboratory procedures. Chemical Rubber Company, Cleveland, p 345

  • Flora SJS (2002) Nutritional components modify metal absorption, toxic response and chelation therapy. J Nutr Environ Med 12:53–67

    CAS  Google Scholar 

  • Flora G, Gupta D, Tiwari A (2012) Toxicity of lead: a review with recent updates. Interdiscip Toxicol 5:47–58

    PubMed  PubMed Central  CAS  Google Scholar 

  • 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

  • Halazun KJ, Aldoori A, Malik HZ (2008) Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol 34(1):55–60

    PubMed  CAS  Google Scholar 

  • Hashem MA, El-Sharkawy NI (2009) Haematobiochemical and immunotoxicological effects of low electromagnetic field and its interaction with lead in mice. Iraqi J Vet Sci 23:105–114

    Google Scholar 

  • Ibrahim NM, Eweis EA, El-Bertagi HS, Abdel-Mobdy YE (2012) Effect of lead acetate toxicity on experimental male albino rat. Asian Pac J Trop Biomed 2(1):41–46

    PubMed  PubMed Central  CAS  Google Scholar 

  • 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(3):1–7

    Google Scholar 

  • Jalali MS, Seyedeh NH, Mousavi M (2017) Comparative effect of silymarin and D-penicillamine on lead induced hemotoxicity and oxidative stress in rat. Iran J Toxicol 11(3):12–18

    Google Scholar 

  • John JB (2005) Chronic venous insufficiency and the therapeutic effects of Daflon 500 mg. Angiology 56(6):21–24

    Google Scholar 

  • Kasemy ZA, Kamel GM, Abdel-Rasoul GM, Ismail AA (2019) Environmental and health effects of benzene exposure among Egyptian taxi drivers. J Environ Public Health 4(10):707–802

    Google Scholar 

  • Keleiny EG, Ibrahim Laila IM, Ibrahim SR (2019) The effect of ferulic acid against lead induced oxidative stress and DNA damage in kidney and testes of rats. Environ Sci Pollut Res 26:31675–31684

    Google Scholar 

  • Khan SY, Arshad M, Arshad N, Shaafat S, Tahir HM (2016) A probable role of blood lead levels on some haematological parameters in traffic police, Lahore Pakistan. Toxicol Ind Health 32:795–800

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Mager EM (2012) Homeostasis and toxicology of non-essential metals. In: Wood CM, Anthony P, Farrell, Brauner CJ (eds) Fish physiology, notably, lead decreased PCV, Hb, RBC, MCV, and MCHC by 66.75%, 144.30%, 233.61%, 95.522%, and 94.68% respectively while the administration of DAF improved PCV, Hb, RBC, MCV, and MCHC by 45.03%, 104.30%, 227.46%, 67.80%, and 59.50% respectively. Elsevier Incorporation, New York, pp 85–236

  • Magyar JS, Weng TC, Stern CM, Dye DF, Rous BW, Payne JC, Bridgewater BM (2005) Re-examination of lead (II) coordination preferences in sulphur-rich sites: implications for a critical mechanism of lead poisoning. J Am Chem Soc 127(6):9495–9505

    PubMed  CAS  Google Scholar 

  • Martins JA, Gustavo RB, Anna JB, Marilesia FS (2015) Effects of lead exposure and genetic polymorphisms on ALAD and GPx activities in Brazillian battery workers. J Toxicol Environ Health 78(16):1–9

    Google Scholar 

  • Minka NS, Ayo JO (2007) Physiological responses of transported goats treated with ascorbic acid during the hot-dry season. Anim Sci J 78(2):164–172

    CAS  Google Scholar 

  • Mitra P, Sharma P (2019) Novel direction in mechanisms underlying lead toxicity: evidence and prospective. Indian J Clin Biochem 34:121–122

    PubMed  PubMed Central  Google Scholar 

  • Ohyashiki T, Kobayashi M, Mashi K (1991) Antioxidants in lead toxicity. Arch Biochem Biophys 228:282–286

    Google Scholar 

  • 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(2):31–37

    Google Scholar 

  • Onalaja AO, Claudio L (2000) Genetic susceptibility to lead poisoning. Environ Health Perspect 108:23–28

    PubMed  PubMed Central  CAS  Google Scholar 

  • Orisakwe OE, Oladipo OO, Ajaezi GC, Udowelle NA (2017) Horizontal and vertical distribution of heavy metals in farm produce and livestock around lead-contaminated goldmine in Dareta and Abare, Zamfara state, Northern Nigeria Journal of Environmental and Public.Health

  • Oyewale JO (1991) Osmotic fragility of erythrocytes of guinea fowls at 21 and 156 weeks of age. Veterinariski Arhiv 61(1):49–56

    Google Scholar 

  • Patrick L (2006) Lead toxicity, a review of the literature. Part 1: exposure, evaluation, and treatment. Altern Med Rev 11:2–22

    PubMed  Google Scholar 

  • Pitsch A (2011) The place of Daflon-500mg in recent guidelines on the management of chronic venous disease. Medicograhia 33(3):306–314

    Google Scholar 

  • Ramlet AA (2001) Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency. Angiology 52:49–56

    Google Scholar 

  • 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(6):1121–1126

    PubMed  CAS  Google Scholar 

  • Rous P (2000) The effect of heavy metals boundary contaminated soil on haematological and selected biochemical parameters in blood plasma of rabbits. Acta-Universitatis-Agriculturae-et-SilviculturaeMendelianae-Brunensis 48(3):93–99

    CAS  Google Scholar 

  • Sakai T, Morita Y (1996) Delta aminolevulinic acid in plasma or whole blood as a sensitive indicator of lead effects, and its relation to the other heme-related parameters. Int Arch Occup Environ Health 68:126–132

    PubMed  CAS  Google Scholar 

  • Sancar F (2019) Childhood lead exposure may affect personality, mental health in adulthood. JAMA 32(15):1445–1446

    Google Scholar 

  • Shraideh AZ, Badran HD, Hunaiti AA, Battahn A (2019) Delta-aminolevulinic acid dehydratase inhibition and RBC abnormalities in relation to blood lead among selected Jordanian workers. Jordan J Biol Sci 12(2):237–241

    CAS  Google Scholar 

  • Supabhorn Y, Donrawee W, Saruda K (2019) Screening for elevated blood lead levels and related risk factors among Thai children residing in a fishing community. Toxics 7:54

    Google Scholar 

  • 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 

  • Terao J (2009) Dietary flavonoids as antioxidants. Forum Nutr 61:87–94

    PubMed  CAS  Google Scholar 

  • Timchalk C, Lin Y, Witz KK, Wu H, Gies RA, Moore DA, Yantasee W (2006) Disposition of lead (Pb) in saliva and blood of Sprague-Dawley rats following single or repeated oral exposure to Pb-acetate. Toxicology 222(1–2):86–94

    PubMed  CAS  Google Scholar 

  • Unlu BZ, Singletary KW, Murphy LL, Venema RC, Young AJ (2003) Phytonutrients differentially stimulate NAD(P)H: quinone oxidoreductase, inhibit proliferation, and trigger mitotic catastrophe in Hepa1c1c7 cells. J Med Food 19(1):47–53

    Google Scholar 

  • Warang P, Colah R, Kedar P (2017) Lead poisoning induced severe hemolytic anaemia, basophilic stippling, mimicking erythrocyte pyrimidine 5′-nucleotidase deficiency in beta thalassemia minor. J Clin Toxicol 7(2):346

    Google Scholar 

  • WHO (2010) Action is needed on chemicals of major public health concern. Public Health Environmental pp 1–4. Available online: https://www.who.int/ipcs/assessment/public_health/chemicals_phc/en/

  • Yusuf IL, Akefe IO, Tijjani MB, Yusuf H, Salihu SI, Muhammad Z (2018) Lead-induced increase in erythrocyte osmotic fragility and malondialdehyde concentration in Wistar rats: chemo-protective effects of flavonoid mixture. Biochem Biotechnol Res 6(1):9–14

    Google Scholar 

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Authors and Affiliations

  1. Veterinary Pharmacology and Toxicology, University of Maiduguri, Maiduguri, Nigeria

    Ibrahim Yusuf Lamidi & Sabo Isa Salihu

  2. Veterinary Pharmacology and Toxicology, University of Abuja, Abuja, Nigeria

    Mikail Garba Hudu

  3. Veterinary Physiology, Biochemistry and Pharmacology, University of Jos, Jos, Nigeria

    Isaac Oluwatobi Akefe

  4. Veterinary Pathology, Ahmadu Bello University Zaria, Zaria, Nigeria

    Sani Adamu

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  1. Ibrahim Yusuf Lamidi
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Correspondence to Ibrahim Yusuf Lamidi.

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Lamidi, I.Y., Hudu, M.G., Akefe, I.O. et al. 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 29, 955–963 (2020). https://doi.org/10.1007/s00580-020-03144-6

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