Skip to main content Skip to main navigation menu Skip to site footer

Subchronic toxicity of piperine in piper nigrum on the histology of the kidney, liver, and lungs of mice (Mus musculus L.)

  • Sri Nabawiyati Nurul Makiyah ,
  • Sri Tasminatun ,
  • Puguh Novi Arsito ,
  • Khairina Nurul Fauziah ,
  • Dieny Rizka Nugrahanti ,
  • Annisa Putriani ,

Abstract

Introduction: Piperine is a compound that has many health benefits, but piperin has toxic effects that endanger the human body. The purpose of this study was to determine the toxic dose of subchronic piperine administration using histology of the liver, kidneys, and lungs of mice (Mus musculus L).

Method: This is a quasi-experimental research with posttest only control group design.  Thirty male BALB/c mice were divided into five groups. Piperine was administered orally to the mice. The normal control group and four treatment groups at dosage of 17.5, 35, 70, and 140 mg/kg body weight for 21 days. At the day-22, the liver, kidneys, and lungs were removed and prepared using the HE staining technique. Scores of liver, kidney, and lung damage are recorded. The data was analyzed using one-way ANOVA with the post hoc Tukey test.

Result: The liver histological damage score after administration of piperine doses of 35, 70, and 140 mg/kg significantly different from the control group. The kidney and lung damage scores after 140 mg/kg administration showed significant differences from the control group. The conclusion is piperine at dosage of 35, 70, and 140 mg/kg was toxic to the liver, and piperine at doses of 140 mg/kg was toxic to the kidney and lung histology of BALB/c mice.

Conclusion: Piperine should not be used at doses of 35 mg/kg body weight or larger.

References

  1. Parasuraman S. Toxicological screening. J Pharmacol Pharmacother. 2011;2(2):74–9. Available from: https://pubmed.ncbi.nlm.nih.gov/21772764
  2. Gosselin S, Ramaiah L, Earl L. Clinical Chemistry in Toxicity Testing: Scope and Methods. In: General and Applied Toxicology. John Wiley & Sons, Ltd; 2009. Available from: http://dx.doi.org/10.1002/9780470744307.gat040
  3. Taqvi SIH, Shah AJ, Gilani AH. Blood Pressure Lowering and Vasomodulator Effects of Piperine. J Cardiovasc Pharmacol. 2008;52(5):452–8. Available from: http://dx.doi.org/10.1097/fjc.0b013e31818d07c0
  4. Ahmad N, Fazal H, Abbasi BH, Rashid M, Mahmood T, Fatima N. Efficient regeneration and antioxidant potential in regenerated tissues of Piper nigrum L. Plant Cell, Tissue Organ Cult. 2010;102(1):129–34. Available from: http://dx.doi.org/10.1007/s11240-010-9712-x
  5. Makhov P, Golovine K, Canter D, Kutikov A, Simhan J, Corlew MM, et al. Co-administration of piperine and docetaxel results in improved anti-tumor efficacy via inhibition of CYP3A4 activity. Prostate. 2011/07/27. 2012;72(6):661–7. Available from: https://pubmed.ncbi.nlm.nih.gov/21796656
  6. Nirwane AM, Bapat AR. Effect of methanolic extract of Piper nigrum fruits in Ethanol-CCl4 induced hepatotoxicity in Wistar rats. Der Pharm Lett. 2012;4(3):795–802.
  7. Parganiha R, Verma S, Chandrakar S, Pal S, Sawarkar HA, Kashyap P. In vitro anti-asthmatic activity of fruit extract of Piper nigrum (Piperaceae). Inter J Herb Drug Res. 2011;1:15–8.
  8. Sunila ES, Kuttan G. Immunomodulatory and antitumor activity of Piper longum Linn. and piperine. J Ethnopharmacol. 2004;90(2–3):339–46. Available from: http://dx.doi.org/10.1016/j.jep.2003.10.016
  9. Bent S. Herbal medicine in the United States: review of efficacy, safety, and regulation: grand rounds at University of California, San Francisco Medical Center. J Gen Intern Med. 2008/04/16. 2008;23(6):854–9. Available from: https://pubmed.ncbi.nlm.nih.gov/18415652
  10. Pizzorno J. The kidney dysfunction epidemic, part 1: Causes. Integr Med. 2015;14(6):8–13.
  11. Kasarala G, Tillmann HL. Standard liver tests. Clin liver Dis. 2016;8(1):13–8. Available from: https://pubmed.ncbi.nlm.nih.gov/31041056
  12. Dogra RKS, Khanna S, Shanker R. Immunotoxicological effects of piperine in mice. Toxicology. 2004;196(3):229–36. Available from: http://dx.doi.org/10.1016/j.tox.2003.10.006
  13. Piyachaturawat P, Glinsukon T, Toskulkao C. Acute and subacute toxicity of piperine in mice, rats and hamsters. Toxicol Lett. 1983;16(3–4):351–9. Available from: http://dx.doi.org/10.1016/0378-4274(83)90198-4
  14. Kotyk T, Dey N, Ashour AS, Balas-Timar D, Chakraborty S, Ashour AS, et al. Measurement of glomerulus diameter and Bowman’s space width of renal albino rats. Comput Methods Programs Biomed. 2016;126:143–53. Available from: http://dx.doi.org/10.1016/j.cmpb.2015.10.023
  15. Zakaria DM, Zahran NM, Arafa SAA, Mehanna RA, Abdel-Moneim RA. Histological and Physiological Studies of the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Bleomycin Induced Lung Fibrosis in Adult Albino Rats. Tissue Eng Regen Med. 2020/10/22. 2021;18(1):127–41. Available from: https://pubmed.ncbi.nlm.nih.gov/33090319
  16. Mordue DG, Monroy F, La Regina M, Dinarello CA, Sibley LD. Acute Toxoplasmosis Leads to Lethal Overproduction of Th1 Cytokines. J Immunol. 2001;167(8):4574–84. Available from: http://dx.doi.org/10.4049/jimmunol.167.8.4574
  17. Ganesh Bhat B, Chandrasekhara N. Studies on the metabolism of piperine: Absorption, tissue distribution and excretion of urinary conjugates in rats. Toxicology. 1986;40(1):83–92. Available from: http://dx.doi.org/10.1016/0300-483x(86)90048-x
  18. Baratawidjaja IR, Baratawidjaja PP, Darwis A, Yi FC, Chew FT, Lee BW, et al. Mites in Jakarta homes. Allergy. 1998;53(12):1226–7. Available from: http://dx.doi.org/10.1111/j.1398-9995.1998.tb03849.x
  19. SOEKSMANTO A. Effect of Butanol Extract of Maturated Mahkota Dewa (Phaleria macrocarpa) Fruit on Liver Tissue of Mice (Mus musculus). Biodiversitas J Biol Divers. 2006;7(4). Available from: http://dx.doi.org/10.13057/biodiv/d070408
  20. Septiva EB, Sitasiwi AJ, Isdadiyanto S. Struktur Mikroanatomi Ginjal Mencit (Mus Musculus L.) Betina Setelah Paparan Ekstrak Etanol Daun Mimba (Azadirachta indica A. Juss). Pro-Life. 2019;6(2):180–90.
  21. Sclera [Internet]. Jubb, Kennedy & Palmer’s Pathology of Domestic Animals. Elsevier; 2007. p. 532. Available from: http://dx.doi.org/10.1016/b978-070202823-6.50061-0
  22. Suhita NLPR, Sudira IW, Winaya IBO. Histopatologi Ginjal Tikus Putih Akibat Pemberian Ekstrak Pegagan (Centella asiatica) Peroral. Bul Vet Udayana. 2013;5(1):63–9.
  23. Sudjarwo SA, Sudjarwo GW, Koerniasari. Protective effect of curcumin on lead acetate-induced testicular toxicity in Wistar rats. Res Pharm Sci. 2017;12(5):381–90. Available from: https://pubmed.ncbi.nlm.nih.gov/28974976
  24. Fahrimal Y, R R, Aliza D. Gambaran Histopatologis Ginjal Tikus Putih (Rattus novergicus) Jantan yang Diinfeksikan Trypanosoma vvansi dan Diberi Ekstrak Daun Sernai (Wedelia biflora). J Med Vet. 2016;8(1). Available from: http://dx.doi.org/10.21157/j.med.vet..v10i2.4386
  25. Kolhe SR, Borole P, Patel U. Extraction and Evaluation of Piperine from Piper nigrum Linn. Int J Appl Biol Pharm Technol. 2011;2(2):144–9.
  26. Lengkong AB. Gambaran Histopatologik Hati Tikus Wistar Yang Diinduksi Ccl4 Dan Diberi Air Rebusan Tanaman Cakar Ayam (Selaginella Doederleinii Hieron). J e-Biomedik. 2013;1(2). Available from: http://dx.doi.org/10.35790/ebm.1.2.2013.5482
  27. Manatar AF, Wangko S, Kaseke MM. Gambaran Histologik Hati Tikus Wistar Yang Diberi Virgin Coconut Oil Dengan Induksi Parasetamol. J BIOMEDIK. 2013;5(1). Available from: http://dx.doi.org/10.35790/jbm.5.1.2013.2608
  28. Abbas AK, Aster JC, Kumar V, Robbins SL. Robbins Basic Pathology. 2013. 18–92 p.
  29. Moldoveanu B, Otmishi P, Jani P, Walker J, Sarmiento X, Guardiola J, et al. Inflammatory mechanisms in the lung. J Inflamm Res. 2009;2:1–11.
  30. Chertov O, Yang D, Howard OMZ, Oppenheim JJ. Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses. Immunol Rev. 2000;177(1):68–78. Available from: http://dx.doi.org/10.1034/j.1600-065x.2000.17702.x
  31. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012/01/13. 2012;5(1):9–19. Available from: https://pubmed.ncbi.nlm.nih.gov/23268465
  32. Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem. 2014/07/15. 2015;30(1):11–26. Available from: https://pubmed.ncbi.nlm.nih.gov/25646037
  33. Chandler DB. Possible Mechanisms of Bleomycin-Induced Fibrosis. Clin Chest Med. 1990;11(1):21–30. Available from: http://dx.doi.org/10.1016/s0272-5231(21)00669-9
  34. Reinert T, Baldotto CS da R, Nunes FAP, Scheliga AA de S. Bleomycin-Induced Lung Injury. J Cancer Res. 2013;2013:1–9. Available from: http://dx.doi.org/10.1155/2013/480608
  35. Marianti A. Aktivitas Antioksidan Jus Tomat pada Pencegahan Kerusakan Jaringan Paru-Paru Mencit yang Dipapar Asap Rokok (Genetic Diversity of Banana with B Genom Using Microsatelite Marker). Biosaintifika J Biol Biol Educ. 2009;1(1):1–7.
  36. Fidler IJ. Targeting of immunomodulators to mononuclear phagocytes for therapy of cancer. Adv Drug Deliv Rev. 1988;2(1):69–106. Available from: http://dx.doi.org/10.1016/0169-409x(88)90006-3
  37. Bang JS, Oh DH, Choi HM, Sur B-J, Lim S-J, Kim JY, et al. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1beta-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Res Ther. 2009/03/30. 2009;11(2):R49–R49. Available from: https://pubmed.ncbi.nlm.nih.gov/19327174
  38. Principles of Mucosal Immunology. Society for Mucosal Immunology. Edited by Phillip D. Smith, Thomas T. MacDonald, and Richard S. Blumberg. London and New York: Garland Science (Taylor & Francis Group). $90.00 (paper). xxii + 529 p.; ill.; index. ISBN: 978-0-8153-4443-8. 2013. Q Rev Biol. 2013;88(4):364. Available from: http://dx.doi.org/10.1086/673840

How to Cite

Makiyah, S. N. N., Tasminatun, S., Arsito, P. N., Fauziah, K. N., Nugrahanti, D. R., & Putriani, A. (2021). Subchronic toxicity of piperine in piper nigrum on the histology of the kidney, liver, and lungs of mice (Mus musculus L.). Bali Medical Journal, 10(3), 1161–1167. https://doi.org/10.15562/bmj.v10i3.2837

HTML
27

Total
242

Share

Search Panel

Sri Nabawiyati Nurul Makiyah
Google Scholar
Pubmed
BMJ Journal


Sri Tasminatun
Google Scholar
Pubmed
BMJ Journal


Puguh Novi Arsito
Google Scholar
Pubmed
BMJ Journal


Khairina Nurul Fauziah
Google Scholar
Pubmed
BMJ Journal


Dieny Rizka Nugrahanti
Google Scholar
Pubmed
BMJ Journal


Annisa Putriani
Google Scholar
Pubmed
BMJ Journal