Skip to main content
SpringerLink
Log in

Acetaminophen-Induced Nephrotoxicity: Suppression of Apoptosis and Endoplasmic Reticulum Stress Using Boric Acid

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Acetaminophen (APAP) is one of the popular and safe pain medications worldwide. However, due its wide availability, it is frequently implicated in intentional or unintentional overdoses where it can cause severe liver injury and even acute liver failure. Boron is a bioactive trace element, found naturally as boric acid (BA) and borate. In this study, the effects of boric acid on the acute renal toxicity induced by APAP in rats were researched in comparison with N-acetyl cysteine (NAC). In the study, 7 groups were formed and 2 g/kg dose of paracetamol per rat was prepared by suspending in 1% Carboxy Methyl Cellulose (CMC) solution of phosphate buffer saline (PBS). Boric acid dissolved in saline was administered to experimental animals by gavage at doses of 50, 100, and 200 mg/kg. In this study, ER stress and apoptosis formed by paracetamol-induced nephrotoxicity were investigated. This purpose determined iNOS, PERK, ATF6, NFkB p53, caspases 3, 12, bcl-2, and bcl-xL gene mRNA expression kidney tissue. Also, the levels of kidney injury molecule-1 (KIM-1), Cysteine (Cys), and IL-18 levels, which are mentioned today as kidney damage markers were compared with BUN and creatine levels. The effect of boron on kidney damage was determined by histopathologic. Data were statistically analyzed by using SPSS-20 ANOVA and stated as means and standard deviation. According to the data obtained in our study, we believe that boric acid has a protective effect on the negative effects of paracetamol on the kidney. We believe that our study will provide useful data to the literature on the possibility of a supplement to be used as an active compound in paracetamol for the prophylaxis of boric acid and it can also be converted into a useful product.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Lewis RK, Paloucek FP (1991) Assessment and treatment of acetaminophen. Clin pharm 10:765–774

    CAS  Google Scholar 

  2. Spooner JB, Harvey JG (1976) The history and usage of paracetamol. J Int Med Res 4(4_suppl):1–6

  3. Bessems JG, Vermeulen NP (2001) Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Crit Rev Toxicol 31(1):55–138

    Article  CAS  Google Scholar 

  4. Corcoran GB, Mitchell JR, Vaishnav YN, Horning EC (1980) Evidence that acetaminophen and N-hydroxyacetaminophen form a common arylating intermediate, N-acetyl-p-benzoquinoneimine. Mol Pharmacol 18(3):536–542

    CAS  Google Scholar 

  5. Randers E, Erlandsen EJ. Serum cystatin C as an endogenous marker of the renal function–a review. Review Clin Chem Lab Med 37(4):389–395

  6. Gharishvandi F, Kazerouni F, Ghanei E, Rahimipour A, Nasiri M (2015) Comparative assessment of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C as early biomarkers for early detection of renal failure in patients with hypertension. Iran Biomed J 19(2):76

    Google Scholar 

  7. Petzold K, Poster D, Krauer F, Spanaus K, Andreisek G, Nguyen-Kim TD, Pavik I, Ho TA, Serra AL, Rotar L (2015) Urinary biomarkers at early ADPKD disease stage. PLoS One 10(4):e0123555

    Article  Google Scholar 

  8. Acaroz U, Ince S, Arslan-Acaroz D, Gurler Z, Kucukkurt I, Demirel HH, Arslan HO, Varol N, Zhu K (2018) The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats. Food Chem Toxicol 118:745–752

    Article  CAS  Google Scholar 

  9. Coban FK, Ince S, Kucukkurt I, Demirel HH, Hazman O (2015) Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats. Drug Chem Toxicol 38(4):391–399

    Article  CAS  Google Scholar 

  10. James P, Jamshed S, Elkalmi R, AlShami A, Nor A, Kabir F, Sumali I, Zubair A, Shamsudin S (2018) Causes of stress and management approaches among undergraduate pharmacy students: findings from a Malaysian public university. Arch Pharmacy Pract. https://archivepp.com/storage/models/article/OWKxUy7ThmiKWrTfhRjXxD1c1e0J4k0W50xF8hvImW0atkhb5bHGRkL6mwfu/causesof-stress-and-management-approaches-among-undergraduate-pharmacy-students-findings-from-a-m.pdf

  11. Zehra F, Naqvi AA (2017) The Global Halal Pharmaceutical Market: strengths, challenges, and prospects. Arch Pharm Pract 8(3):85–87

    Google Scholar 

  12. Palaian S, Mohamed Ibrahim MI, Mishra P (2016) Development of pharmacovigilance training module for community pharmacists in Nepal: a focus group study. Arch Pharmacy Pract 7(4)

  13. Wei CT, Omar MS (2016) Current practice and determinants of medication management in long term care facilities. Arch Pharmacy Pract 7(3):73–79

    Article  Google Scholar 

  14. Trumper L, Girardi G, Elías MM (1992) Acetaminophen nephrotoxicity in male Wistar rats. Arch Toxicol 66(2):107–111

    Article  CAS  Google Scholar 

  15. Hu JJ, Lee MJ, Vapiwala M, Reuhl K, Thomas PE, Yang CS (1993) Sex-related differences in mouse renal metabolism and toxicity of acetaminophen. Toxicol Appl Pharmacol 122(1):16–26

    Article  CAS  Google Scholar 

  16. Mazer M, Perrone J (2008) Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol 4(1):2–6

    Article  Google Scholar 

  17. Naguib YM, Azmy RM, Samaka RM, Salem MF (2014) Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress in acetaminophen-induced hepato-renal injury. BMC Complement Altern Med 14(1):1–2

    Article  Google Scholar 

  18. 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(1):24–34

    Article  CAS  Google Scholar 

  19. Colak S, Geyikoğlu F, Keles ON, Türkez H, Topal A, Unal B (2011) The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity. Toxicol Ind Health 27(8):700–710

    Article  CAS  Google Scholar 

  20. Ince S, Kucukkurt I, Cigerci IH, Fidan AF, Eryavuz A (2010) The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. J Trace Elem Med Biol 24(3):161–164

    Article  CAS  Google Scholar 

  21. Kucukkurt I, Akbel E, Karabag F, Ince S (2015) The effects of dietary boron compounds in supplemented diet on hormonal activity and some biochemical parameters in rats. Toxicol Ind Health 31(3):255–260

    Article  CAS  Google Scholar 

  22. Samman S, Naghıı MR, Lyons Wall PM, Verus AP (1998) Determining the accumulation level of some elements, especially Baron in the plants growing in close districts of Seydisuyu (Eskişehir). Biol Trace Elem Res 66(1–3):227–235

    Article  CAS  Google Scholar 

  23. Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE (2015) PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics 25(8):416

    Article  CAS  Google Scholar 

  24. Ince S, Turkmen R, Yavuz H (2011) The effect of boric acid on acethylcholine, bethanechol and potasssium-evoked responses on ileum of rat. Auton Autacoid Pharmacol 31(3–4):50–56

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by the Usak University Scientific Research Project Coordination Unit (2017 /MF008), and TUBITAK with the project number of 216S671.

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Science and Literature, Uşak University, 64200, Usak, Turkey

    Funda Karabağ Çoban

  2. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Afyon Kocatepe University, 03030, Afyonkarahisar, Turkey

    Sinan İnce

  3. Department of Pathology, Faculty of Veterinary Medicine, Afyon Kocatepe University, 03030, Afyonkarahisar, Turkey

    Hasan Hüseyin Demirel

  4. Department of Molecular Biology and Genetics, The Graduate School of Natural and Applied Sciences, Uşak University, 64200, Usak, Turkey

    İzzet İslam & Hande Aytuğ

Authors
  1. Funda Karabağ Çoban
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sinan İnce
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hasan Hüseyin Demirel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. İzzet İslam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hande Aytuğ
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.A. was responsible for overall supervision. F.K.Ç., S.İ, H.H.D., İ.İ, and H.A. contributed to all experimental work, data and statistical analysis, and interpretation of data. H.H.D. drafted the manuscript, which was revised. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Funda Karabağ Çoban.

Ethics declarations

Competing Interests

The authors declare no competing interests.

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

Çoban, F.K., İnce, S., Demirel, H.H. et al. Acetaminophen-Induced Nephrotoxicity: Suppression of Apoptosis and Endoplasmic Reticulum Stress Using Boric Acid. Biol Trace Elem Res 201, 242–249 (2023). https://doi.org/10.1007/s12011-022-03114-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-022-03114-9

Keywords

Search

Navigation