Skip to main content
Log in

The protective effect of carvacrol on acetaminophen-induced renal damage in male rats

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Acetaminophen overdose causes renal injury via oxidative stress and apoptosis induction. Carvacrol has several pharmacological properties such as antioxidant, anti-inflammation and anti-apoptotic effect. The aim of this study was to determine the protective effect of carvacrol on acetaminophen-induced renal damage in rats.

Methods and results

Forty male Wistar rats were randomly divided to five groups (n = 8) including control, carvacrol 10 mg/kg, acetaminophen, acetaminophen + carvacrol 5 mg/kg, and acetaminophen + carvacrol 10 mg/kg. Animals received a single dose of acetaminophen (500 mg/kg), then were treated with carvacrol for 1 week (daily). Afterwards, renal blood flow (RBF), mean arterial pressure, renal perfusion pressure, renal vascular resistance (RVR), blood urea nitrogen (BUN), and serum creatinine were measured. Also, malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured in the kidney tissue. Hematoxylin and eosin method was used for histological assessment. The Western blotting analysis was used to determine the Bax, Bcl-2 and cleaved caspase-3 proteins expression level in the kidney tissue. Carvacrol (10 mg/kg) significantly increased the RBF, GPx and SOD activities and also reduced the RVR, serum creatinine, BUN, and MDA in the acetaminophen + carvacrol 10 mg/kg group versus acetaminophen group (P < 0.05). Also, carvacrol significantly decreased the cleaved caspase-3, Bax proteins expression level, and kidney tissue damage score in the acetaminophen + carvacrol 10 mg/kg group versus acetaminophen group (P < 0.05).

Conclusions

This study showed that carvacrol can attenuate the acetaminophen induced acute kidney damage via suppressing oxidative stress and apoptosis biochemical factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Roy S, Pradhan S, Das K, Mandal A, Mandal S, Patra A, Samanta A, Sinha B, Nandi DK (2015) Acetaminophen induced kidney failure in rats: a dose response study. J Biol Sci 15(4):187. https://doi.org/10.3923/jbs.2015.187.193

    Article  CAS  Google Scholar 

  2. Lorz C, Justo P, Sanz A, Subirá D, Egido J, Ortiz A (2004) Paracetamol-induced renal tubular injury: a role for ER stress. J Am Soc Nephrol 15(2):380–389

    Article  CAS  Google Scholar 

  3. Aycan İÖ, Tokgöz O, Tüfek A, Alabalık U, Evliyaoğlu O, Turgut H, Çelik F, Güzel A (2015) The use of thymoquinone in nephrotoxicity related to acetaminophen. Int J Surg 13:33–37. https://doi.org/10.1016/j.ijsu.2014.11.020

    Article  PubMed  Google Scholar 

  4. Mazer M, Perrone J (2008) Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol 4(1):2–6. https://doi.org/10.1007/BF03160941

    Article  PubMed  PubMed Central  Google Scholar 

  5. El-Shafey MM, Abd-Allah GM, Mohamadin AM, Harisa GI, Mariee AD (2015) Quercetin protects against acetaminophen-induced hepatorenal toxicity by reducing reactive oxygen and nitrogen species. Pathophysiology 22(1):49–55. https://doi.org/10.1016/j.pathophys

    Article  CAS  PubMed  Google Scholar 

  6. Kaeidi A, Sahamsizadeh A, Allahtavakoli M, Fatemi I, Rahmani M, Hakimizadeh E, Hassanshahi J (2020) The effect of oleuropein on unilateral ureteral obstruction induced-kidney injury in rats: the role of oxidative stress, inflammation and apoptosis. Mol Biol Rep 47(2):1371–1379. https://doi.org/10.1007/s11033-019-05237-0

    Article  CAS  PubMed  Google Scholar 

  7. Kaeidi A, Taghipour Z, Allahtavakoli M, Fatemi I, Hakimizadeh E, Hassanshahi J (2020) Ameliorating effect of troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats. Naunyn Schmiedeberg’s Arch Pharmacol 393(5):879–888. https://doi.org/10.1007/s00210-019-01801-4

    Article  CAS  Google Scholar 

  8. Hassanshahi J, Mirzahosseini-Pourranjbar A, Hajializadeh Z, Kaeidi A (2020) Anticancer and cytotoxic effects of troxerutin on HeLa cell line: an in-vitro model of cervical cancer. Mol Biol Rep 47(8):6135–6142. https://doi.org/10.1007/s11033-020-05694-y

    Article  CAS  PubMed  Google Scholar 

  9. Butler MS (2008) Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep 25(3):475–516. https://doi.org/10.1039/b514294f

    Article  CAS  PubMed  Google Scholar 

  10. Feher M, Schmidt JM (2003) Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. J Chem Inf Comput Sci 43(1):218–227. https://doi.org/10.1021/ci0200467

    Article  CAS  PubMed  Google Scholar 

  11. Al-Attar AM, Elnaggar MH, Almalki EA (2017) Protective effect of some plant oils on diazinon induced hepatorenal toxicity in male rats. Saudi J Biol Sci 24(6):1162–1171. https://doi.org/10.1016/j.sjbs.2016.10.013

    Article  CAS  PubMed  Google Scholar 

  12. Cai Y, Luo Q, Sun M, Corke H (2004) Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 74(17):2157–2184. https://doi.org/10.1016/j.lfs.2003.09.047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fukumoto L, Mazza G (2000) Assessing antioxidant and prooxidant activities of phenolic compounds. J Agric Food Chem 48(8):3597–3604. https://doi.org/10.1021/jf000220w

    Article  CAS  PubMed  Google Scholar 

  14. Suntres ZE, Coccimiglio J, Alipour M (2015) The bioactivity and toxicological actions of carvacrol. Crit Rev Food Sci Nutr 55(3):304–318. https://doi.org/10.1080/10408398.2011.653458

    Article  CAS  PubMed  Google Scholar 

  15. Kohen R, Nyska A (2002) Invited review: oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 30(6):620–650. https://doi.org/10.1080/01926230290166724

    Article  CAS  PubMed  Google Scholar 

  16. Mandal A, Patra A, Mandal S, Roy S, Mahapatra SD, Mahapatra TD, Paul T, Das K, Mondal KC, Nandi DK (2015) Therapeutic potential of different commercially available synbiotic on acetaminophen-induced uremic rats. Clin Exp Nephrol 19(2):168–177. https://doi.org/10.1007/s10157-014-0971-4

    Article  CAS  PubMed  Google Scholar 

  17. Melo FHC, Moura BA, de Sousa DP, de Vasconcelos SMM, Macedo DS, de Fonteles MMF, de Viana GSB, de Sousa FCF (2011) Antidepressant-like effect of carvacrol (5-isopropyl-2-methylphenol) in mice: involvement of dopaminergic system. Fundam Clin Pharmacol 25(3):362–367. https://doi.org/10.1111/j.1472-8206.2010.00850.x

    Article  CAS  PubMed  Google Scholar 

  18. Uyanoglu M, Canbek M, Ceyhan E, Senturk H, Bayramoglu G, Gunduz O, Ozen A, Turgak O (2011) Preventing organ injury with carvacrol after renal ischemia/reperfusion. J Med Plants Res 5(1):72–80

    Article  CAS  Google Scholar 

  19. Amin F, Memarzia A, Rad HK, Kazerani HR, Boskabady MH (2021) Carvacrol and PPARγ agonist, pioglitazone, affects inhaled paraquat-induced lung injury in rats. Sci Rep 11(1):1–15. https://doi.org/10.1038/s41598-021-87546-8

    Article  CAS  Google Scholar 

  20. Gunes S, Ayhanci A, Sahinturk V, Altay DU, Uyar R (2017) Carvacrol attenuates cyclophosphamide-induced oxidative stress in rat kidney. Can J Physiol Pharmacol 95(7):844–849. https://doi.org/10.1139/cjpp-2016-0450

    Article  CAS  PubMed  Google Scholar 

  21. Hassanshahi J, Nematbakhsh M (2018) The role of Mas receptor on renal hemodynamic responses to angiotensin 1–7 in both irreversible and reversible unilateral ureteral obstruction rats. Adv Biomed Res. https://doi.org/10.4103/abr.abr_176_17

    Article  PubMed  PubMed Central  Google Scholar 

  22. Samimiat A, Khosravi MS, Hassanshahi J, Nematbakhsh M (2018) The effect of AT2 and Mas receptors antagonists on renal hemodynamic and excretory disorders induced by ischemia/reperfusion in male and female rats. Physiol Pharmacol 22(2):133–140

    Google Scholar 

  23. Hantz H, Adesuyi A, Adebayo O (2001) Differential effects of U46619 on renal regional hemodynamics in the rat: involvement of endothelin. J Pharmacol Exp Ther 299(1):372–376

    CAS  PubMed  Google Scholar 

  24. Hassanshahi J, Maleki M, Nematbakhsh M (2018) Renal blood flow and vascular resistance responses to angiotensin II in irreversible and reversible unilateral ureteral obstruction rats; the role of angiotensin II type 1 and 2 receptors. J Nephropathol 7(2):57–64

    Article  Google Scholar 

  25. Richard MJ, Portal B, Meo J, Coudray C, Hadjian A, Favier A (1992) Malondialdehyde kit evaluated for determining plasma and lipoprotein fractions that react with thiobarbituric acid. Clin Chem 38(5):704–709

    Article  CAS  Google Scholar 

  26. Ōyanagui Y (1984) Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Anal Biochem 142(2):290–296. https://doi.org/10.1016/0003-2697(84)90467-6

    Article  PubMed  Google Scholar 

  27. Flohé L, Günzler WA (1984) [12] Assays of glutathione peroxidase. Methods Enzymol 105:114–120

    Article  Google Scholar 

  28. Wang B, Liu D, Zhu Q-h, Li M, Chen H, Guo Y, Fan L-p, Yue L-s, Li L-y, Zhao M (2016) Rutin ameliorates kidney interstitial fibrosis in rats with obstructive nephropathy. Int Immunopharmacol 35:77–84. https://doi.org/10.1016/j.intimp.2016.03.029

    Article  CAS  PubMed  Google Scholar 

  29. Sancak EB, Tan YZ, Turkon H, Silan C (2017) Attenuation of partial unilateral ureteral obstruction–induced renal damage with hyperbaric oxygen therapy in a rat model. Int Braz J Urol 43(5):946–956. https://doi.org/10.1590/S1677-5538.IBJU.2016.0565

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pakravan N, Bateman DN, Goddard J (2007) Effect of acute paracetamol overdose on changes in serum and urine electrolytes. Br J Clin Pharmacol 64(6):824–832. https://doi.org/10.1111/j.1365-2125.2007.02952.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Trumper L, Girardi G, Elías MM (1992) Acetaminophen nephrotoxicity in male Wistar rats. Arch Toxicol 66(2):107–111. https://doi.org/10.1111/j.1472-8206.2009.00768.x

    Article  CAS  PubMed  Google Scholar 

  32. Chiam E, Bellomo R, Churilov L, Weinberg L (2018) The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: a single center placebo controlled randomized study. PLoS ONE 13(4):e0195931

    Article  Google Scholar 

  33. Wang B, Yang X, Yu H, Man X (2020) The comparison of ibuprofen versus acetaminophen for blood pressure in preeclampsia: a meta-analysis of randomized controlled studies. J Matern Fetal Neonatal Med. https://doi.org/10.1080/14767058.2020.1720641

    Article  PubMed  Google Scholar 

  34. Peixoto-Neves D, Silva-Alves K, Gomes M, Lima F, Lahlou S, Magalhães P, Ceccatto V, Coelho-de-Souza A, Leal-Cardoso J (2010) Vasorelaxant effects of the monoterpenic phenol isomers, carvacrol and thymol, on rat isolated aorta. Fundam Clin Pharmacol 24(3):341–350. https://doi.org/10.1111/j.1472-8206.2009.00768.x

    Article  CAS  PubMed  Google Scholar 

  35. Gheitasi I, Azizi A, Omidifar N, Doustimotlagh AH (2020) Renoprotective effects of Origanum majorana methanolic L and carvacrol on ischemia/reperfusion-induced kidney injury in male rats. Evid Based Complement Altern Med. https://doi.org/10.1155/2020/9785932

    Article  Google Scholar 

  36. Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N (2016) Acetaminophen-induced hepatotoxicity: a comprehensive update. J Clin Transl Hepatol 4(2):131. https://doi.org/10.14218/JCTH.2015.00052

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bozkurt M, Em S, Oktayoglu P, Turkcu G, Yuksel H, Sarıyıldız MA, Caglayan M, Batmaz İ, Nas K, Bozkurt Y (2014) Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats. Clin Invest Med. https://doi.org/10.25011/cim.v37i1.20865

    Article  PubMed  Google Scholar 

  38. Suganthi RU, Manpal S (2013) Biological and pharmacological of actions carvacrol and its effects on poultry: an updated review. World J Pharm Pharm Sci 2(2013):3581–3595

    Google Scholar 

  39. Potočnjak I, Domitrović R (2016) Carvacrol attenuates acute kidney injury induced by cisplatin through suppression of ERK and PI3K/Akt activation. Food Chem Toxicol 98:251–261. https://doi.org/10.1016/j.fct.2016.11.004

    Article  CAS  PubMed  Google Scholar 

  40. El-Sayed EM, Abd-Allah AR, Mansour AM, EL-Arabey AM (2015) Thymol and carvacrol prevent cisplatin-induced nephrotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats. J Biochem Mol Toxicol 29(4):165–172. https://doi.org/10.1002/jbt.21681

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by Rafsanjan University of Medical Sciences (Grant # 97301).

Author information

Authors and Affiliations

Authors

Contributions

Conceived and designed the experiments: JH. Performed the experiments: AK, JH, MR, and AN. Analyzed the data: JH and MR. Contributed reagents/materials/analysis tools: EH, and JH. Wrote the paper: AN, JH and AK.

Corresponding author

Correspondence to Jalal Hassanshahi.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Consent to participate

All authors voluntarily agreed to participate in this study.

Consent to publish

All authors voluntarily agreed to publish the results of this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Najafizadeh, A., Kaeidi, A., Rahmani, M. et al. The protective effect of carvacrol on acetaminophen-induced renal damage in male rats. Mol Biol Rep 49, 1763–1771 (2022). https://doi.org/10.1007/s11033-021-06985-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06985-8

Keywords

Navigation