Environmental Science and Pollution Research

, Volume 26, Issue 31, pp 31675–31684 | Cite as

The effect of ferulic acid against lead-induced oxidative stress and DNA damage in kidney and testes of rats

  • Eman G. Kelainy
  • Ibrahim M. Ibrahim Laila
  • Shaimaa R. IbrahimEmail author
Research Article


Oxidative stress is an imbalance between free radicals and antioxidants which leads to reactive oxygen species (ROS) production in cells. Reactive oxygen species contains oxygen radicals that easily react with other molecules in the biological system. For decades, lead acetate (Pb(C2H3O2)2) is used as an additive for many widely used chemical products such as insecticides, hair dyes, and cosmetics; however, contact with lead acetate may irritate skin, eyes, and mucous membranes.

In the present study, the antioxidant and anti-inflammatory effect of using ferulic acid to inhibit lead acetate-induced toxicity in rats is investigated. Lead acetate was orally given at a dose of 20 mg/kg body weight for 10 days, either alone or with ferulic acid at dose 25 mg/kg. Serum luteinizing hormone (LH), total testosterone, and follicle-stimulating hormone (FSH) levels were measured. Also, reactive oxygen species (ROS), lipid peroxidation (LPO), total antioxidant capacity (TAC), and catalase (CAT) activities were determined. In addition, histopathological changes of testes and kidney were examined. Results showed that administration of lead acetate induced oxidative stress through attenuation of luteinizing hormone, total testosterone, and follicle-stimulating hormone levels in serum. Moreover, the kidney and testes of lead acetate-treated animals exhibited elevation of ROS level, lipid peroxide levels, as well as lysosomal enzyme activity such acid phosphatase and N-acetyl-β-glucosminidase. DNA fragmentation and histological changes were also observed in lead acetate-treated group. In contrast, ferulic acid treatment reduced the deleterious effects induced by lead acetate in both testes and kidney tissues. These results illustrated that ferulic acid has a protective action against toxicity caused by lead acetate in rats. In conclusions, ferulic acid may have future therapeutic relevance in the prevention of lead acetate-induced testicular and renal toxicity in rats.


Lead Ferulic acid Oxidative stress Lysosome enzyme DNA damage 


Conflict of interest

The authors declare that they have no conflicts of interest.


Anesthetic procedures and handling with animals were complied with the ethical guidelines of the Medical Ethical Committee of the National Organization for Drug Control and Research in Egypt and performed for being sure that the animals do not suffer at any stage of the experiment.


  1. Abdel Moneim AE (2016) Indigofera oblongifolia prevents lead acetate-induced hepatotoxicity, oxidative stress, fibrosis and apoptosis in rats. PLOS ONE8,1–18. Google Scholar
  2. Abdel Moneim AE, Dkhil MA, Al-Quraishy S (2011) The protective effect of flaxseed oil on lead acetate-induced renal toxicity in rats. J Hazard Mater 194:250–255Google Scholar
  3. Abdel-Wahhab M, Aly S (2005) Antioxidant property of Nigella sativa (black cumin) and Syzygiumaromaticum (clove) in rats during aflatoxicosis. J Appl Toxicol 25:218–223Google Scholar
  4. Adam A, Crespy V, Levrat-Verny MA, Leenhardt F, Leuillet M, Demigne C, Remesy C (2002) The bioavailability of ferulic acids governed primarily by the food matrix rather than its metabolism in intestine and liver in rats. J Nutr 132:1962–1968Google Scholar
  5. Ahmed MM, Elmenoufy G (2016) Ameliorative effect of ferulic acid on acrylamide induced inflammation and oxidative damage in rat testes. Res J Pharm, Biol Chem Sci 7(1):396–403Google Scholar
  6. Ahmed MA, Farid OAA, Shehata AM (2016) A Neuroprotective role for ferulic acid against acrylamide-induced neurotoxicity in rats. J Global Biosci Issn 2320-1355 5(2):3635–3644Google Scholar
  7. Azza H, Entesar A, Saber RF, Ahmad Arafat HFH, El-Demerdash RS (2017) Comparison of ferulic acid and sildenafil, therapeutic role against testicular injury induced by cadmium chloride in adult male albino rat. Int J Res Stud Biosci 5(1, January):6–15Google Scholar
  8. Banchroft D, Stevens A, Turner DR (1996) Theory and practice of histological techniques, 4th edn. Churchil Livingstone, New York, London, San Francisco, Tokyo. (92), pp 122–128Google Scholar
  9. Barnham KJ, Cappai R, Beyreuther K (2006) Delineating common molecular mechanisms in Alzheimer’s and prion diseases. Trends Biochem Sci 31:465–472Google Scholar
  10. Barone E, Calabrese V, Mancuso C (2009) Ferulic acid and its therapeutic potential as a hermetic for age related disease. Biogerontology. 10:97–108Google Scholar
  11. Biswas NM, Ghosh PK (2006) Protection of adrenal and male gonadal functions by androgen in lead treated rats. Kathmandu Univ Med J 14:1218–12 21Google Scholar
  12. Bondy SC (1996) Oxygen generation as a basis for neurotoxicity of metals. In: Toxicology of metals, Chang, L.W. Ends,RC Press, Baco Raton, pp 699–706Google Scholar
  13. D’Archivio M, Filesi C, Di Benedetto R (2007) Polyphenols, dietary sources and bioavailability. Ann Its Super Sanita 43:348–361Google Scholar
  14. Dai S, Yin Z, Yuan G, Lu H, Jia R, Xu J, Song X, Li L, Shu Y, Liang X, He C, Lv C (2013) Quantification of metallothionein on the liver and kidney of rats by subchronic lead and cadmium in combination. Environ Toxicol Pharmacol J 36:1207–1216Google Scholar
  15. Dehpour AZ, Ghafourifar P, Ahangari N (1996) Inhibition by lithium and rubidium of gentamicin-induced release of N-acetyl -P-D-glucosaminidase from perfused rat kidney. Toxicol. 110:9–15Google Scholar
  16. Draper HH, Squires EJ, Mahmoodi H, Wu J, Agarwal S, Hadley MA (1993) Comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials. Free Rad Boil Med 15:353–363Google Scholar
  17. El-Tantawy WH (2015) Antioxidant effects of Spirulina supplement against lead acetate-induced hepatic injury in rats. J Tradit Complement Med 6(4):327–331Google Scholar
  18. Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 1(6):529–539Google Scholar
  19. Gajawat S, Sancheti G, Goyal PK (2006) Protection against lead induced hepatic lesions in swiss albino mice by ascorbic acid. Pharmacologyonline 1:140–149Google Scholar
  20. Garcia MTA, Gonzalez ELM (2008) Toxic effects of perinatal lead exposure on the brain of rats: involvement of oxidative stress and the beneficial role of antioxidants. Food ChemToxicol 46:2089–2095Google Scholar
  21. Graf E (1992) Antioxidant potential of ferulic acid. Free RadicBiol Med 13(4):435–448Google Scholar
  22. Gurer-Orhan H, Sabir HU, Ozgüneş H (2004) Correlation between clinical indicators of lead poisoning and oxidative stress parameters in controls and lead-exposed workers. Toxicol. 195:147–154Google Scholar
  23. Hamadouche AN, Slimani M, Merad-Boudia BZC (2009) Reproductive toxicity of lead acetate in adult male rats. Am J Sci Res 3:38–50Google Scholar
  24. Heim KE, Tagliaferro AR, Bobliya DJ (2002) Flavonoid antioxidants: chemistry, metabolism and structure activity relationships. J Nutr Biochem 13:572–558Google Scholar
  25. Hultberg B, Andersson A, Isaksson A (2001) Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol. Toxicol. 156:93–100Google Scholar
  26. Jabeen R, Tahir M, Waqas S (2010) Teratogenic effects of lead acetate on kidney. J Ayub Med Coll Abbottabad 22(1):76–79Google Scholar
  27. Janakiraman S, Arumugam K, Reddy VB, Nagarajan RP (2012) Ferulic acid, a dietary phenolic acid, modulates radiation effects in swiss albino mice. Eur J Pharmacol 691(1-3):268–274Google Scholar
  28. Jegede AI, Ajadi MB, Akinloye O (2013) Modulatory effects of Kolaviron (Garcina kola extract) on spermogram and reproductive system of adult male Wistar rats in lead acetate induced toxicity. J Toxicol Environ Health Sci 5(7):121–130Google Scholar
  29. Jia Q, Ha X, Yang Z, Hui L, Yang X (2012) Oxidative stress: a possible mechanism for lead-induced apoptosis and nephrotoxicity. Toxicol Mech Methods 22(9):705–710Google Scholar
  30. Kanski J, Aksenova M, Stoyanova A, Butterfield DA (2002) Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure activity studies. J Nutr Biochem v 13(5):273–281Google Scholar
  31. Kiewlicz J, Szymusiak H, Zieliński R (2015) Symthesis. Thermal stability and antioxidant activity of long-chain alkyl esters of ferulic acid. Zywn Nauk Technol Ja 4:188–200Google Scholar
  32. Kilikdar D, Mukherjee D, Mitra E, Ghosh AK, Basu A, Chandra AM, Bandyopadhyay D, Indian J (2011) Protective effect of aqueous garlic extract against lead-induced hepatic injury in rats. Exp. 49:498–510Google Scholar
  33. Kojima H, Ohi H, Miyaji H, Seki M, Fujita T, Hatano M (1987) Localization of C3d in renal tissues of patients with membranous nephropathy and IgA nephropathy. Nihon JinzoGakkai Shi 29(9):1161–1165Google Scholar
  34. Koracevic D, Koracevic G (2001) Colorimetric method for determination of total antioxidant capacity kits. J Clin Pathol 54:356–361Google Scholar
  35. Kroon PA, Faulds CB, Ryden P, Robertson JA, Williamson G (1997) Release of covalently bound ferulic acid from fiber in the human colon. J Agric Food Chem 45(3):661–667Google Scholar
  36. Lodi S, Sharma V, Kansal L (2011) The protective effect of Rubia cordifolia against lead nitrate-induced immune response impairment and kidney oxidative damage. Indian J Pharmacol 43:441–444Google Scholar
  37. Loghman-Adham M (1997) Renal effects of environmental and occupational lead exposure. Environ Health Perspect 105(9):928–938 Epub/09/25Google Scholar
  38. Marchlewicz M, Michalska T, Wiszniewska B (2004) Detection of lead-induced oxidative stress in the rat epididymis by chemiluminescence. chemosphere 57:1553–1562Google Scholar
  39. Patrick L (2006) Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Alter Med Rev 11:2–22Google Scholar
  40. Rastogi SK (2008) Renal effects of environmental and occupational lead exposure. Ind J Occup Environ Med 12:103–106Google Scholar
  41. Rechner AR, Pannala AS, Rice-Evans CA (2001) Caffeic acid derivatives in artichoke extract are metabolised to phenolic acids in vivo. Free Radic Res 35(2):195–202Google Scholar
  42. Robin CR, William BW (1978) The temperature-dependence of the loss of latency of lysosomal enzymes. Biochem J 172:163–173Google Scholar
  43. Roy S, Metya SK, Rahaman N, Sannigrahi S, Ahmed F (2014) Ferulic acid in the treatment of post-diabetes testicular damage: relevance to the downregulation of apoptosis correlates with antioxidant status via modulation of TGF-β1, IL- 1β and Akt signaling. Cell Biochem Funct 32:115–124Google Scholar
  44. Sambrook JE, Fritsch D, Maniutis T (1989) “Molecular cloning” A laboratory manual 2nd Ed. Cold Spring Harbor Laboratory Press USA, Cold Spring Harbor, pp 63–66Google Scholar
  45. Shukla PK, Khanna VK, Khan MY, Srimal RC (2003) Protective effect of curcumin against lead neurotoxicity in rat. Hum ExpToxicol 22:653–658Google Scholar
  46. Silbergeld EK, Waalkes M, Rice JM (2000) Lead as a carcinogen: experimental evidence and mechanisms of action. Am J Ind Med 38:316–323Google Scholar
  47. Sinha AK (1972) Calorometric assay of catalase. Anal Biochem 47:389–394Google Scholar
  48. Sirnivasan R, Chandraseker MJN, Nanjan MJ, Suresh B (2007) Antioxidant activity of Caesalpinia digyna root. J Ethnopharmacol 113:284–291Google Scholar
  49. Sokol RZ (1987) Hormonal effects of lead acetate in the male rat. Mechanism of action. Biol Reprod 37:1135–1138Google Scholar
  50. Szkoda J, Zmudzki J (2005) Determination of lead and cadmium in biological material by graphite furnace atomic absorption spectrometry method. Bull Vet Inst Pulawy 49:89–92Google Scholar
  51. Szweda PA, Friguet B, Szweda LI (2002) Proteolysis, free radicals and aging. Free Radic Biol Med 33:29–36Google Scholar
  52. Tanaka K, Iizuka Y (1968) Suppressive of enzyme release from isolated rat liver lysosomes by non-osteroidal anti-inflammatory drugs. Biochem Pharmacol 17:2023–2032Google Scholar
  53. Tee-ngam P, Nunant N, Rattanarat P, Siangproh W, Chailapakul O (2013) Simple and rapid determination of ferulic acid levels in food and cosmetic samples using paper-based platforms. Sensors. 13:13039–13053Google Scholar
  54. Tsuji LJS, Karagatzides JD (2001) Chronic lead exposure, body condition and testes mass in wild mallard ducks. Bull Environ Contam Toxicol 67:489–495Google Scholar
  55. Van Hoof F, Hers HG (1968) The abnormalities of lysosomal enzymes in mucopolysaccharides. Eur J Biochem 7:34–44Google Scholar
  56. Vrablic AS, Albright CD, Craciunescu CN, Salanik RI, Zesel SH (2001) Altered mitochondrial function and over generation of reactive oxygen species precede the induction of apoptosis by 1-O-octadecyl-2-methyl-racglycero-3-phosphocholine in p53-defective hepatocytes. Fed Am Soc Exp Biol 15:1739–1744Google Scholar
  57. Waters M, Stasiewicz S, Merrick BA, Tomer K, Bushel P, Paules R, Stegman N, Nehls G, Yost KJ, Johnson CH (2008) CEBS – Chemical Effects in Biological Systems: a public data repository integrating study design and toxicity data with microarray and proteomics data. Nucleic Acids Res36, D892–D900. Google Scholar
  58. Winder C (1989) Reproductive and chromosomal effect of occupational exposure to lead on the male. Reprod Toxicol 3:221–233Google Scholar
  59. Wolfe KL, Liu RH (2008) Structure–activity relationships of flavonoids in the cellular antioxidant activity assay. J Agric Food Chem 56:8404–8411Google Scholar
  60. Zbakh H, Abbassi AE (2012) Potential use of olive mill wastewater in the preparation of functional beverages: a review. J Funct Foods 4:450–458Google Scholar
  61. Zduńska K, Dana A, Kolodziejczak A, Rotsztejn H (2018) Antioxidant properties of ferulic acid and its possible application. Skin Pharmacol Physiol 31:332–336Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Eman G. Kelainy
    • 1
  • Ibrahim M. Ibrahim Laila
    • 1
  • Shaimaa R. Ibrahim
    • 1
    Email author
  1. 1.Department of Molecular Drug EvaluationNational Organization for Drug Control & Research (NODCAR)GizaEgypt

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