Healing potential of Adiantum capillus-veneris L. plant extract on bisphenol A-induced hepatic toxicity in male albino rats

  • Qudsia Kanwal
  • Abdul Qadir
  • Amina
  • Asmatullah
  • Hafiza Hira Iqbal
  • Bushra Munir
Research Article


Bisphenol A (BPA) is a widely used environmental pollutant in the production of plastics but causes hepatotoxicity in mammals. In the present study, we studied the BPA-induced oxidative stress in rats and ameliorative potential of Adiantum capillus-veneris L. plant. It was concluded that the BPA can reduce the body and liver weight, increase in biochemical levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total bilirubin, and disturb the normal hepatic physiology, histology, and metabolism. Additionally, liver histology shows hepatic necrosis, congestion, and vacuolization in exposed individuals. In contrast, simultaneous exposure of A. capillus-veneris and BPA showed declining trend in serum biomarker levels and normal histopathological structures. We conclude that the A. capillus-veneris plant is antioxidant in nature and can reduce the BPA-induced toxicity. These findings are very helpful to understand the BPA-induced hepatic toxicity and ameliorative potential of A. capillus-veneris plant and are of great importance in risk assessment of xenobiotics.


A. capillus-veneris L. Bisphenol A (BPA) Hepatic injury Rats Restoration 



Special thanks are given to the laboratory assistants for their help during experiment and analyses.

Compliance with ethical standards

The protocol of the study was approved by the departmental ethical committee of animal experiments, College of Earth and Environmental Sciences (CEES), University of the Punjab.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abbasi AM, Shah MH, Li T, Fu X, Guo X, & Liu, RH (2015) Ethnomedicinal values, phenolic contents and antioxidant properties of wild culinary vegetables. J Ethnopharmacol 162:333-345Google Scholar
  2. Ahmed A, Wadud A, Jahan N, Bilal A, Hajera S (2013) Efficacy of Adiantum capillus veneris Linn in chemically induced urolithiasis in rats. J Ethnopharmacol 146(1):411–416.  https://doi.org/10.1016/j.jep.2013.01.011 CrossRefGoogle Scholar
  3. Ahmed W et al (2015) Bisphenol A toxicity in adult male rats: hematological, biochemical and histopathological approach. Glob Veternaria 14:228–238Google Scholar
  4. Akingbemi BT (2005) Estrogen regulation of testicular function. Reprod Biol Endocrinol 3(1):51.  https://doi.org/10.1186/1477-7827-3-51 CrossRefGoogle Scholar
  5. Al-Hiyasat AS, Darmani H, Elbetieha AM (2002) Effects of bisphenol A on adult male mouse fertility. Eur J Oral Sci 110(2):163–167.  https://doi.org/10.1034/j.1600-0722.2002.11201.x CrossRefGoogle Scholar
  6. Angulo P, Keach JC, Batts KP, Lindor KD (1999) Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30(6):1356–1362.  https://doi.org/10.1002/hep.510300604 CrossRefGoogle Scholar
  7. Ansari R, & Ekhlasi-Kazaj K (2012) Adiantum capillus-veneris. L: Phytochemical Constituents, Traditional Uses and Pharmacological Properties: A Review. J Adv Sci Res 3(4):15-20Google Scholar
  8. Asahi J, Kamo H, Baba R, Doi Y, Yamashita A, Murakami D, Hanada A, Hirano T (2010) Bisphenol A induces endoplasmic reticulum stress-associated apoptosis in mouse non-parenchymal hepatocytes. Life Sci 87(13):431–438.  https://doi.org/10.1016/j.lfs.2010.08.007 CrossRefGoogle Scholar
  9. Atcha Z, Rourke C, Neo AH, Goh CW, Lim JS, Aw CC, Browne ER, Pemberton DJ (2010) Alternative method of oral dosing for rats. J Am Assoc Lab Anim Sci 49(3):335–343Google Scholar
  10. Bancroft JD, & Gamble M (2008) Theory and Practice of Histopathological Techniques. (6th ed.). Elsevier Health Sciences, LondonGoogle Scholar
  11. Berkowitz G (2006) Limitations of a case–control study on bisphenol A (BPA) serum levels and recurrent miscarriage. Hum Reprod 21(2):565–566.  https://doi.org/10.1093/humrep/dei335 CrossRefGoogle Scholar
  12. Bindhumol V, Chitra KC, Mathur PP (2003) Bisphenol A induces reactive oxygen species generation in the liver of male rats. Toxicology 188(2):117–124.  https://doi.org/10.1016/S0300-483X(03)00056-8 CrossRefGoogle Scholar
  13. Chen Z, Zuo X, He D, Ding S, Xu F, Yang H, Jin X, Fan Y, Ying L, Tian C, Ying C (2017) Long-term exposure to a ‘safe’dose of bisphenol A reduced protein acetylation in adult rat testes. Sci Rep 7:40337.  https://doi.org/10.1038/srep40337 CrossRefGoogle Scholar
  14. Chitra K et al (2003) Induction of oxidative stress by bisphenol A in the epididymal sperm of rats. Toxicology 185(1):119–127.  https://doi.org/10.1016/S0300-483X(02)00597-8 CrossRefGoogle Scholar
  15. Crookham JN, & Dapson RW (1991) Hazardous Chemicals in the Histopathology Laboratory: Regulations Risks Handling & Disposal. AnatechGoogle Scholar
  16. Dekant W, Völkel W (2008) Human exposure to bisphenol A by biomonitoring: methods, results and assessment of environmental exposures. Toxicol Appl Pharmacol 228(1):114–134.  https://doi.org/10.1016/j.taap.2007.12.008 CrossRefGoogle Scholar
  17. El Tawab AMA et al (2014) Protective effect of Satureja montana extract on cyclophosphamide-induced testicular injury in rats. Chem Biol Interact 224:196–205.  https://doi.org/10.1016/j.cbi.2014.11.001 CrossRefGoogle Scholar
  18. Frye C, Bo E, Calamandrei G, Calzà L, Dessì-Fulgheri F, Fernández M, Fusani L, Kah O, Kajta M, le Page Y, Patisaul HB, Venerosi A, Wojtowicz AK, Panzica GC (2012) Endocrine disrupters: a review of some sources, effects, and mechanisms of actions on behaviour and neuroendocrine systems. J Neuroendocrinol 24(1):144–159.  https://doi.org/10.1111/j.1365-2826.2011.02229.x CrossRefGoogle Scholar
  19. Gangadharan L, Valenzuela MR (2001) Interrelationships between income, health and the environment: extending the Environmental Kuznets Curve hypothesis. Ecol Econ 36(3):513–531.  https://doi.org/10.1016/S0921-8009(00)00250-0 CrossRefGoogle Scholar
  20. Giboney PT (2005) Mildly elevated liver transaminase levels in the asymptomatic patient. Am Fam Physician 71(6):1105–1110Google Scholar
  21. Gurmeet KSS, Rosnah I, Normadiah MK, Das S, Mustafa AM (2014). Detrimental effects of bisphenol A on development and functions of the male reproductive system in experimental rats. EXCLI J 13:151Google Scholar
  22. Haider S, Nazreen S, Alam MM, Gupta A, Hamid H, Alam MS (2011) Anti-inflammatory and anti-nociceptive activities of ethanolic extract and its various fractions from Adiantum capillus veneris Linn. J Ethnopharmacol 138(3):741–747.  https://doi.org/10.1016/j.jep.2011.10.012 CrossRefGoogle Scholar
  23. Hassan ZK, Elobeid MA, Virk P, Omer SA, ElAmin M, Daghestani MH, AlOlayan EM (2012) Bisphenol A induces hepatotoxicity through oxidative stress in rat model. Oxidative Med Cell Longev 2012:1–6.  https://doi.org/10.1155/2012/194829 CrossRefGoogle Scholar
  24. HIROI H, Tsutsumi O, Takeuchi T, Momoeda M, Ikezuki Y, OKamura A, Yokota H, Taketani Y (2004) Differences in serum bisphenol a concentrations in premenopausal normal women and women with endometrial hyperplasia. Endocr J 51(6):595–600.  https://doi.org/10.1507/endocrj.51.595 CrossRefGoogle Scholar
  25. Ho Y-S, Magnenat JL, Gargano M, Cao J (1998) The nature of antioxidant defense mechanisms: a lesson from transgenic studies. Environ Health Perspect 106(Suppl 5):1219–1228.  https://doi.org/10.1289/ehp.98106s51219 CrossRefGoogle Scholar
  26. Hussein RM, & Eid JI (2013) Pathological mechanisms of liver injury caused by oral administration of bisphenol A. Life Sci J 10(1)Google Scholar
  27. Ibraheim ZZ, Ahmed AS, Gouda YG (2011) Phytochemical and biological studies of Adiantum capillus-veneris L. Saudi Pharm J 19(2):65–74.  https://doi.org/10.1016/j.jsps.2011.01.007 CrossRefGoogle Scholar
  28. Inoue H, Yokota H, Makino T, Yuasa A, Kato S (2001) Bisphenol A glucuronide, a major metabolite in rat bile after liver perfusion. Drug Metab Dispos 29(8):1084–1087Google Scholar
  29. Inoue H, Yuki G, Yokota H, Kato S (2003) Bisphenol A glucuronidation and absorption in rat intestine. Drug Metab Dispos 31(1):140–144.  https://doi.org/10.1124/dmd.31.1.140 CrossRefGoogle Scholar
  30. Izzotti A, Longobardi M, Cartiglia C, D'Agostini F, Kanitz S, de Flora S (2010) Pharmacological modulation of genome and proteome alterations in mice treated with the endocrine disruptor bisphenol A. Curr Cancer Drug Targets 10(2):147–154.  https://doi.org/10.2174/156800910791054220 CrossRefGoogle Scholar
  31. Jayashree S, Indumathi D, Akilavalli N, Sathish S, Selvaraj J, Balasubramanian K (2013) Effect of bisphenol-A on insulin signal transduction and glucose oxidation in liver of adult male albino rat. Environ Toxicol Pharmacol 35(2):300–310.  https://doi.org/10.1016/j.etap.2012.12.016 CrossRefGoogle Scholar
  32. Kabuto H, Amakawa M, Shishibori T (2004) Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and causes underdevelopment of the brain and testis in mice. Life Sci 74(24):2931–2940.  https://doi.org/10.1016/j.lfs.2003.07.060 CrossRefGoogle Scholar
  33. Keshavan P, Schwemberger SJ, Smith DLH, Babcock GF, Zucker SD (2004) Unconjugated bilirubin induces apoptosis in colon cancer cells by triggering mitochondrial depolarization. Int J Cancer 112(3):433–445.  https://doi.org/10.1002/ijc.20418 CrossRefGoogle Scholar
  34. Kleiner DE, Brunt EM, van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ, Nonalcoholic Steatohepatitis Clinical Research Network (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41(6):1313–1321.  https://doi.org/10.1002/hep.20701 CrossRefGoogle Scholar
  35. Korkmaz A, Ahbab MA, Kolankaya D, Barlas N (2010) Influence of vitamin C on bisphenol A, nonylphenol and octylphenol induced oxidative damages in liver of male rats. Food Chem Toxicol 48(10):2865–2871.  https://doi.org/10.1016/j.fct.2010.07.019 CrossRefGoogle Scholar
  36. Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, Melzer D (2008) Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA 300(11):1303–1310.  https://doi.org/10.1001/jama.300.11.1303 CrossRefGoogle Scholar
  37. Lee YJ, Ryu HY, Kim HK, Min CS, Lee JH, Kim E, Nam BH, Park JH, Jung JY, Jang DD, Park EY, Lee KH, Ma JY, Won HS, Im MW, Leem JH, Hong YC, Yoon HS (2008) Maternal and fetal exposure to bisphenol A in Korea. Reprod Toxicol 25(4):413–419.  https://doi.org/10.1016/j.reprotox.2008.05.058 CrossRefGoogle Scholar
  38. Marmugi A, Lasserre F, Beuzelin D, Ducheix S, Huc L, Polizzi A, Chetivaux M, Pineau T, Martin P, Guillou H, Mselli-Lakhal L (2014) Adverse effects of long-term exposure to bisphenol A during adulthood leading to hyperglycaemia and hypercholesterolemia in mice. Toxicology 325:133–143.  https://doi.org/10.1016/j.tox.2014.08.006 CrossRefGoogle Scholar
  39. Matsumoto J, Yokota H, Yuasa A (2002) Developmental increases in rat hepatic microsomal UDP-glucuronosyltransferase activities toward xenoestrogens and decreases during pregnancy. Environ Health Perspect 110(2):193–196.  https://doi.org/10.1289/ehp.02110193 CrossRefGoogle Scholar
  40. Morgan AM, el-Ballal SS, el-Bialy BE, el-Borai NB (2014) Studies on the potential protective effect of cinnamon against bisphenol A-and octylphenol-induced oxidative stress in male albino rats. Toxicol Rep 1:92–101.  https://doi.org/10.1016/j.toxrep.2014.04.003 CrossRefGoogle Scholar
  41. Mourad IM, Khadrawy YA (2012) The sensetivity of liver, kidney andtestis of rats to oxidative stress induced by different doses of bisphenol A. Life 50:19Google Scholar
  42. Muñoz-de-Toro M, Markey CM, Wadia PR, Luque EH, Rubin BS, Sonnenschein C, Soto AM (2005) Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice. Endocrinology 146(9):4138–4147.  https://doi.org/10.1210/en.2005-0340 CrossRefGoogle Scholar
  43. Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM (2007) Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure. Reprod Toxicol 23(3):383–390.  https://doi.org/10.1016/j.reprotox.2006.10.002
  44. Nandi D, Patra RC, Swarup D (2005) Effect of cysteine, methionine, ascorbic acid and thiamine on arsenic-induced oxidative stress and biochemical alterations in rats. Toxicology 211(1):26–35.  https://doi.org/10.1016/j.tox.2005.02.013 CrossRefGoogle Scholar
  45. Paulose C, Dakshinamurti K (1987) Chronic catheterization using vascular-access-port in rats: blood sampling with minimal stress for plasma catecholamine determination. J Neurosci Methods 22(2):141–146.  https://doi.org/10.1016/0165-0270(87)90008-2 CrossRefGoogle Scholar
  46. Politch JA (2006) Bisphenol A and risk assessment. Environ Health Perspect 114(1):A16.  https://doi.org/10.1289/ehp.114-a16a CrossRefGoogle Scholar
  47. Pourmorad F, Hosseinimehr SJ, & Shahabimajd N (2006) Antioxidant activity, phenol and flavonoid contents of some selected Iranian medicinal plants. Afr J Biotechnol 5(11)Google Scholar
  48. Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28(1):56–63.  https://doi.org/10.1093/ajcp/28.1.56 CrossRefGoogle Scholar
  49. Richter CA et al (2007) In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol 24(2):199–224CrossRefGoogle Scholar
  50. Rochester JR (2013) Bisphenol A and human health: a review of the literature. Reprod Toxicol 42:132–155.  https://doi.org/10.1016/j.reprotox.2013.08.008 CrossRefGoogle Scholar
  51. Sangai NP, Verma RJ (2011) Quercetin alleviates bisphenol A-induced changes in nucleic acid and protein contents in mice. Acta Pol Pharm Drug Res 68:867–873Google Scholar
  52. Schuler P (1990) Natural antioxidants exploited commercially. Food antioxidants. Springer, Berlin, pp 99–170Google Scholar
  53. Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S (2002) Stimulation of CD25+ CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 3(2):135–142.  https://doi.org/10.1038/ni759 CrossRefGoogle Scholar
  54. Singh M, Singh N, Khare PB, Rawat AKS (2008) Antimicrobial activity of some important Adiantum species used traditionally in indigenous systems of medicine. J Ethnopharmacol 115(2):327–329.  https://doi.org/10.1016/j.jep.2007.09.018 CrossRefGoogle Scholar
  55. Snyder RW, Maness SC, Gaido KW, Welsch F, Sumner SCJ, Fennell TR (2000) Metabolism and disposition of bisphenol A in female rats. Toxicol Appl Pharmacol 168(3):225–234.  https://doi.org/10.1006/taap.2000.9051 CrossRefGoogle Scholar
  56. Strassburg C et al (2002) Developmental aspects of human hepatic drug glucuronidation in young children and adults. Gut 50(2):259–265.  https://doi.org/10.1136/gut.50.2.259 CrossRefGoogle Scholar
  57. Stump DG, Beck MJ, Radovsky A, Garman RH, Freshwater LL, Sheets LP, ... & Shiotsuka RN (2010) Developmental neurotoxicity study of dietary bisphenol A in Sprague-Dawley rats. Toxicol Sci 115(1):167-182Google Scholar
  58. Sugiura-Ogasawara M, Ozaki Y, Sonta Si, Makino T, Suzumori K (2005) Exposure to bisphenol A is associated with recurrent miscarriage. Hum Reprod 20(8):2325–2329.  https://doi.org/10.1093/humrep/deh888 CrossRefGoogle Scholar
  59. Swaroop K et al (2012) Influence of ethanolic leaf extract of Sargassum wightii and Adiantum capillus on histamine induced asthma in animal model. Int J Pharm Pharm Sci 4(4):121–123Google Scholar
  60. Takeuchi T et al (2004) Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction. Endocr J 51(2):165–169.  https://doi.org/10.1507/endocrj.51.165 CrossRefGoogle Scholar
  61. Tan BL et al (2003) Assessment of pubertal development in juvenile male rats after sub-acute exposure to bisphenol A and nonylphenol. Toxicol Lett 143(3):261–270.  https://doi.org/10.1016/S0378-4274(03)00172-3 CrossRefGoogle Scholar
  62. Tyl R et al (2002) Three-generation reproductive toxicity study of dietary bisphenol A in CD Sprague-Dawley rats. Toxicol Sci 68(1):121–146.  https://doi.org/10.1093/toxsci/68.1.121 CrossRefGoogle Scholar
  63. Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV (2007) Human exposure to bisphenol A (BPA). Reprod Toxicol 24(2):139–177.  https://doi.org/10.1016/j.reprotox.2007.07.010 CrossRefGoogle Scholar
  64. Yousaf B, Amina LG, Wang R, Qadir A, Ali MU, Kanwal Q, Munir B, Asmatullah AZ (2016) Bisphenol A exposure and healing effects of Adiantum capillus-veneris. Environ Sci Pollut Res 23(12):11645–11657.  https://doi.org/10.1007/s11356-016-6330-0 CrossRefGoogle Scholar
  65. Zade VS, et al (2013) Effect of aqueous extract of Moringa oleifera seed on sexual activity of male albino rats. Int J Bio ForumGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Environmental Toxicology Laboratory, College of Earth and Environmental SciencesUniversity of the PunjabLahorePakistan
  2. 2.Developmental Biology Laboratory, Department of ZoologyUniversity of the PunjabLahorePakistan
  3. 3.University of Health SciencesLahorePakistan

Personalised recommendations