Environmental Science and Pollution Research

, Volume 26, Issue 1, pp 240–249 | Cite as

Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue

  • Ahmed AbdeenEmail author
  • Afaf Abdelkader
  • Mohamed Abdo
  • Gamal Wareth
  • Mohamed Aboubakr
  • Lotfi Aleya
  • Mohamed Abdel-Daim
Research Article


Acetaminophen, APAP, is a common over-the-counter drug with antipyretic-analgesic action. When APAP is used in large doses, it causes hepatotoxicity and nephrotoxicity but safe at therapeutic doses. Cinnamon (Cinnamomum zeylanicum) is extensively used in folk medicine due to its high content of natural antioxidants. The current investigation was planned to study the possible ameliorative effect of cinnamon toward induced APAP-apoptosis and cellular damage in renal cells. Four groups (nine rats each) were used; negative control group administrated distilled water for 15 days; positive control APAP group administrated a single dose of APAP (1 g/kg) orally on the last day; APAP+Cin L (200 mg/kg) and APAP+Cin H (400 mg/kg) aqueous extract of cinnamon orally once a day for 15 days. An hour after the last dose of cinnamon, all rats in the third and fourth group were administrated a single dose of APAP (1 g/kg) orally. GC/MS analysis was performed to identify the plant used in the study. APAP markedly increased serum levels of creatinine, BUN, and glucose and decreased levels of albumin and total protein. In addition, APAP could also exert severe alteration in the kidney histopathology along with upregulation of caspase-3 and PCNA. However, pre-treatment with cinnamon ameliorated the APAP-induced cellular alterations and apoptosis, possibly through its high content of antioxidants.


Acetaminophen Nephrotoxicity Cinnamomum zeylanicum GC/MS Free radical Antioxidant Anti-apoptosis Caspase-3 PCNA 



All authors are appreciating the technical support provided by the staff members of the Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University for implementing this study.

Compliance with ethical standards

All the procedures related to animal experimentation were performed according to the guide for the care and use of laboratory animals of the National Institutes of Health (NIH publication No. 85–23, revised 1996) on the protection of animals used for scientific purposes and approved by the ethics committee, Faculty of Veterinary Medicine, Benha University, Egypt.


  1. Abdeen A, Ghonim A, El-Shawarby R et al (2017) Protective effect of cinnamon against cadmium-induced hepatorenal oxidative damage in rats. Int J Pharmacol Toxicol 5:17. CrossRefGoogle Scholar
  2. Abdel-Daim MM, Abdeen A (2018) Protective effects of rosuvastatin and vitamin E against fipronil-mediated oxidative damage and apoptosis in rat liver and kidney. Food Chem Toxicol 114:69–77. CrossRefGoogle Scholar
  3. Abdel-Daim M, Abushouk AI, Reggi R, Yarla NS, Palmery M, Peluso I (2017) Association of antioxidant nutraceuticals and acetaminophen (paracetamol): friend or foe? J Food Drug Anal 26:1–10. CrossRefGoogle Scholar
  4. Al-Sayed E, Abdel-Daim MM, Kilany OE et al (2015) Protective role of polyphenols from Bauhinia hookeri against carbon tetrachloride-induced hepato- and nephrotoxicity in mice. Ren Fail 37:1198–1207. CrossRefGoogle Scholar
  5. Bakkali F, Averbeck S, Averbeck D, Idaomar M (2008) Biological effects of essential oils - a review. Food Chem Toxicol 46:446–475. CrossRefGoogle Scholar
  6. Bessems JGM, Vermeulen NPE (2001) Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Crit Rev Toxicol 31:55–138. CrossRefGoogle Scholar
  7. Canayakin D, Bayir Y, Kilic Baygutalp N, Sezen Karaoglan E, Atmaca HT, Kocak Ozgeris FB, Keles MS, Halici Z (2016) Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa. Pharm Biol 54:2082–2091. CrossRefGoogle Scholar
  8. Coulombe JJ, Favreau L (1963) A new simple semimicro method for colorimetric determination of urea. Clin Chem 9:102–108Google Scholar
  9. Das J, Ghosh J, Manna P, Sil PC (2010) Taurine protects acetaminophen-induced oxidative damage in mice kidney through APAP urinary excretion and CYP2E1 inactivation. Toxicology 269:24–34. CrossRefGoogle Scholar
  10. Dorri M, Hashemitabar S, Hosseinzadeh H (2018) Cinnamon (Cinnamomum zeylanicum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug Chem Toxicol 41:1–14. CrossRefGoogle Scholar
  11. Elkomy A, Aboubakr M, Soliman A, Abdeen A, Abdelkader A, Hekal H (2016) Paracetamol induced hepatic toxicity and amelioration by cinnamon in rats. Int J Pharmacol Toxicol 4:187. CrossRefGoogle Scholar
  12. Elkomy A, Aboubakr M, Ashraf L (2017) Ameliorative effect of thymus oil on paracetamol induced hepato-renal toxicity: a biochemical, antioxidant and histopathological studies. J Pharmacol Clin Res.
  13. El-Maddawy ZK, El-Sayed YS (2018) Comparative analysis of the protective effects of curcumin and N-acetyl cysteine against paracetamol-induced hepatic, renal, and testicular toxicity in Wistar rats. Environ Sci Pollut Res 25:3468–3479.
  14. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. CrossRefGoogle Scholar
  15. Foti M, Piattelli M, Baratta MT, Ruberto G (1996) Flavonoids, coumarins, and cinnamic acids as antioxidants in a micellar system. Structure–activity relationship. J Agric Food Chem 44:497–501. CrossRefGoogle Scholar
  16. Galvan DL, Green NH, Danesh FR (2017) The hallmarks of mitochondrial dysfunction in chronic kidney disease. Kidney Int 92:1051–1057. CrossRefGoogle Scholar
  17. Ghosh J, Das J, Manna P, Sil PC (2010) Acetaminophen induced renal injury via oxidative stress and TNF-α production: therapeutic potential of arjunolic acid. Toxicology 268:8–18. CrossRefGoogle Scholar
  18. Gülçin İ (2011) Antioxidant activity of eugenol: a structure-activity relationship study. J Med Food 14:975–985. CrossRefGoogle Scholar
  19. Hafizur RM, Hameed A, Shukrana M, Raza SA, Chishti S, Kabir N, Siddiqui RA (2015) Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro. Phytomedicine 22:297–300. CrossRefGoogle Scholar
  20. Helal A, Tagliazucchi D (2018) Impact of in-vitro gastro-pancreatic digestion on polyphenols and cinnamaldehyde bioaccessibility and antioxidant activity in stirred cinnamon-fortified yogurt. LWT - Food Sci Technol 89:164–170. CrossRefGoogle Scholar
  21. Hwang ES, Thi ND (2014) Effects of extraction and processing methods on antioxidant compound contents and radical scavenging activities of laver (Porphyra tenera). Prev Nutr Food Sci 19:40–48. CrossRefGoogle Scholar
  22. Iniabohs OM (2017) All rights reserved protective effects of aqueous extract of cinnamon on diabetes-induced nephrotoxicity in Wistar rats. J Appl Sci Environ Manag 21:504–508Google Scholar
  23. Jayaprakasha GK, Rao LJM (2011) Chemistry, biogenesis, and biological activities of cinnamomum zeylanicum. Crit Rev Food Sci Nutr 51:547–562. CrossRefGoogle Scholar
  24. Jayaprakasha GK, Rao LJ, Sakariah KK (2002) Chemical composition of volatile oil from Cinnamomum zeylanicum buds. Zeitschrift fur Naturforsch - Sect C J Biosci 57:990–993. CrossRefGoogle Scholar
  25. Jayaprakasha GK, Negi PS, Jena BS, Jagan Mohan Rao L (2007) Antioxidant and antimutagenic activities of Cinnamomum zeylanicum fruit extracts. J Food Compos Anal 20:330–336. CrossRefGoogle Scholar
  26. Kamaliroosta L (2012) Extraction of cinnamon essential oil and identification of its chemical compounds. J Med Plants Res 6:609–614. CrossRefGoogle Scholar
  27. Karthivashan G, Kura AU, Arulselvan P, Md. Isa N, Fakurazi S (2016) The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model. PeerJ 4:e2127. CrossRefGoogle Scholar
  28. Kaul PN, Bhattacharya AK, Rajeswara Rao BR, Syamasundar KV, Ramesh S (2003) Volatile constituents of essential oils isolated from different parts of cinnamon (Cinnamomum zeylanicum Blume). J Sci Food Agric 83:53–55. CrossRefGoogle Scholar
  29. Kelman Z (1997) PCNA: Structure, functions and interactions. Oncogene 14:629–640.
  30. Larsen K (1972) Creatinine assay by a reaction-kinetic principle. Clin Chim Acta 41:209–217CrossRefGoogle Scholar
  31. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  32. Lv C, Yuan X, Zeng H-W, Liu RH, Zhang WD (2017) Protective effect of cinnamaldehyde against glutamate-induced oxidative stress and apoptosis in PC12 cells. Eur J Pharmacol 815:487–494. CrossRefGoogle Scholar
  33. Madkour FF, Abdel-Daim MM (2013) Hepatoprotective and antioxidant activity of Dunaliella salina in paracetamol-induced acute toxicity in rats. Indian J Pharm Sci 75:642–648. CrossRefGoogle Scholar
  34. Mamoru S, Kazuyuki H (1977) A new colorimetric method for determination of serum glucose. Clin Chim Acta 75:387–391. CrossRefGoogle Scholar
  35. Mazer M, Perrone J (2008) Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol 4:2–6. CrossRefGoogle Scholar
  36. 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 Reports 1:92–101. CrossRefGoogle Scholar
  37. Mour G, Feinfeld DA, Caraccio T, McGuigan M (2005) Acute renal dysfunction in acetaminophen poisoning. Ren Fail 381-383(2005):381–383. CrossRefGoogle Scholar
  38. Murad HAS, Habib H, Kamel Y, Alsayed S, Shakweer M, Elshal M (2016) Thearubigins protect against acetaminophen-induced hepatic and renal injury in mice: biochemical, histopathological, immunohistochemical, and flow cytometry study. Drug Chem Toxicol 39:190–198. CrossRefGoogle Scholar
  39. Ozbek E (2012) Induction of oxidative stress in kidney. Int J Nephrol 2012:1–9. CrossRefGoogle Scholar
  40. Pooja A, Arun N, Maninder K (2013) GC-MS profile of volatile oils of Cinnamomum zeylanicum Blume and Ocimum kilimandscharicum baker ex Gurke. Int J Pharm Sci Rev Res 19:124–126Google Scholar
  41. Ranasinghe P, Pigera S, Premakumara GS et al (2013) Medicinal properties of “true” cinnamon (Cinnamomum zeylanicum): a systematic review. BMC Complement Altern Med 13:275. CrossRefGoogle Scholar
  42. Reshi MS, Shrivastava S, Jaswal A, Sinha N, Uthra C, Shukla S (2017) Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats. Exp Toxicol Pathol 69:231–240. CrossRefGoogle Scholar
  43. Sanz AB, Santamaria B, Ruiz-Ortega M, Egido J, Ortiz A (2008) Mechanisms of renal apoptosis in health and disease. J Am Soc Nephrol 19:1634–1642. CrossRefGoogle Scholar
  44. Sharma UK, Sharma AK, Pandey AK (2016) Medicinal attributes of major phenylpropanoids present in cinnamon. BMC Complement Altern Med 16:1–11. CrossRefGoogle Scholar
  45. Sharma UK, Sharma AK, Gupta A, Kumar R, Pandey A, Pandey AK (2017) Pharmacological activities of cinnamaldehyde and eugenol: antioxidant, cytotoxic and anti-leishmanial studies. Cell Mol Biol 63:73–78. CrossRefGoogle Scholar
  46. Small DM, Coombes JS, Bennett N et al (2012) Oxidative stress, anti-oxidant therapies and chronic kidney disease. Nephrology 17:311–321. CrossRefGoogle Scholar
  47. Wang Z, Hu J, Yan M, Xing JJ, Liu WC, Li W (2017) Caspase-mediated anti-apoptotic effect of ginsenoside Rg5, a main rare ginsenoside, on acetaminophen-induced hepatotoxicity in mice. J Agric Food Chem 65:9226–9236. CrossRefGoogle Scholar
  48. Young T-H, Kao C-Y, Hsieh M-Y, Wang BJ, Hsu JP (2001) Electrophoretic properties of latex particles with immobilized bovine serum albumin. J Colloid Interface Sci 239:563–567CrossRefGoogle Scholar
  49. Yousef MI, Omar SAM, El-Guendi MI, Abdelmegid LA (2010) Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol 48:3246–3261. CrossRefGoogle Scholar
  50. Zhang Y, Zhang F, Wang K, Liu G, Yang M, Luan Y, Zhao Z (2016) Protective effect of allyl methyl disulfide on acetaminophen-induced hepatotoxicity in mice. Chem Biol Interact 249:71–77. CrossRefGoogle Scholar
  51. Zilic S, Serpen A, Akillioglu G et al (2012) Distributions of phenolic compounds, yellow pigments and oxidative enzymes in wheat grains and their relation to antioxidant capacity of bran and debranned flour. J Cereal Sci 56:652–658. CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Forensic Medicine and Toxicology, Faculty of Veterinary MedicineBenha UniversityToukhEgypt
  2. 2.Department of Forensic Medicine and Clinical Toxicology, Faculty of MedicineBenha UniversityBenhaEgypt
  3. 3.Department of Anatomy and Embryology, Faculty of Veterinary MedicineUniversity of Sadat CitySadatEgypt
  4. 4.Department of Pathology, Faculty of Veterinary MedicineBenha UniversityToukhEgypt
  5. 5.Department of Pharmacology, Faculty of Veterinary MedicineBenha UniversityToukhEgypt
  6. 6.Chrono-Environment Laboratory, Bourgogne Franche-Comté UniversityUMR CNRS 6249Besançon CedexFrance
  7. 7.Pharmacology Department, Faculty of Veterinary MedicineSuez Canal UniversityIsmailiaEgypt

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