Skip to main content

Advertisement

Log in

Vitamin B combination reduces fluconazole toxicity in Wistar rats

  • Short Communication
  • Published:
DARU Journal of Pharmaceutical Sciences Aims and scope Submit manuscript

Abstract

Background

The major adverse effect associated with systemic administration of Fluconazole (FLZ), is hepatic toxicity. FLZ is most commonly used antifungal drug in treatment of invasive fungal infections.

Methods

FLZ toxicity was challenged by individual and in combination of three vitamins (B1, B2 B3). Animals were divided nine groups with six animals in each group. FLZ, at a dose of 50 mg/kg b.w, was orally administered for 90 days in experimental animals. Vitamins as individual or in combination was administered concomitantly to challenge or alleviate the toxicity of FLZ. They were sacrificed at the end of protocol for biochemical and histopathology analysis. Focus was made to observe the role of these micro nutrient’s (vitamins) on liver for alteration in of pathological and physiological effects by FLZ in the Wistar albino rats.

Results

Combination of vitamin B1 + B2 + B3 in FLZ induced toxicity was able to restore the level of alkaline phosphatase (ALP) near to normal but with high level of ALP in B1 Control group. Aspartate aminotransferase (AST) was restored to normal in FLZ + B1, FLZ + B2 and FLZ + B1 + B2 + B3 groups and vice versa in FLZ + B3 group animals. Further the level of alanine aminotransferase (ALT) was restored to normal in FLZ + B3 animals. There were no significant changes found in total bilirubin (TBI), and direct bilirubin (DBI) as compare to normal control. Histopathological studies on animals’ studies validated the serological results in normalizing the cellular architecture of liver.

Conclusions

Restoration of altered biochemical parameters and cellular architecture of hepatocytes by different combination of these vitamins proves the chemo preventive potential of these micro nutrients’ in FLZ toxicity.

Vitamin B combination attenuates fluconazole toxicity.

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.

Institutional subscriptions

Fig. 1

References

  1. Cavayas YA, Yusuff H, Porter R. Fungal infections in adult patients on extracorporeal life support. Crit Care. 2018;22(1):98.

    Article  PubMed  PubMed Central  Google Scholar 

  2. O'Leary RA, Einav S, Leone M, Madách K, Martin C, Martin-Loeches I. Management of invasive candidiasis and candidaemia in critically ill adults: expert opinion of the European Society of Anaesthesia Intensive Care Scientific Subcommittee. J Hosp Infect. 2018;98(4):382–90.

    Article  PubMed  Google Scholar 

  3. Cho SY, Lee DG, Choi JK, Lee HJ, Kim SH, Park SH, , Choi SM, Choi JH, Yoo JH, Kim YJ, Kim HJ, Min WS, Back H, Kang S, Lee EK. Cost-benefit analysis of Posaconazole versus FLZ or Itraconazole as a primary antifungal prophylaxis in high-risk hematologic patients: a propensity score-matched analysis. Clin Ther 2015; 37(9): 2019–2027.

    Article  PubMed  Google Scholar 

  4. van Prehn J, Menke-van der Houven van Oordt CW, de Rooij ML, Meijer E, Bomers MK, van Dijk K. Hepatosplenic Candidiasis Without Prior Documented Candidemia: An Underrecognized Diagnosis? Oncologist. 2017;22(8):989–94.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Malhi V, Colburn D, Williams SJ, Hop CE, Dresser MJ, Chandra P, et al. A clinical drug-drug interaction study to evaluate the effect of a proton-pump inhibitor, a combined P-glycoprotein/cytochrome 450 enzyme (CYP)3A4 inhibitor, and a CYP2C9 inhibitor on the pharmacokinetics of vismodegib. Cancer Chemother Pharmacol. 2016;78(1):41–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stefanini I, Rizzetto L, Rivero D, Carbonell S, Gut M, Heath S, et al. Deciphering the mechanism of action of 089, a compound impairing the fungal cell cycle. Sci Rep. 2018;8(1):5964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gearhart MO. Worsening of liver function with FLZ and review of azole antifungal hepatotoxicity. Ann Pharmacother. 1994;28(10):1177–81.

    Article  CAS  PubMed  Google Scholar 

  8. Srichatrapimuk S, Sungkanuparph S. Integrated therapy for HIV and cryptococcosis. AIDS Res Ther. 2016;13(1):42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lonsdale D. Thiamin. Adv Food Nutr Res. 2018;83:1–56.

    Article  PubMed  Google Scholar 

  10. Saedisomeolia A, Ashoori M. Riboflavin in human health: a review of current evidences. Adv Food Nutr Res. 2018;83:57–81.

    Article  PubMed  Google Scholar 

  11. Oka S, Hsu CP, Sadoshima J. Regulation of cell survival and death by pyridine nucleotides. Circ Res. 2012;111(5):611–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Owen B, Brown AD, Kuhlberg J, Millar L, Nichols M, Economos C, et al. Understanding a successful obesity prevention initiative in children under 5 from a systems perspective. PLoS One. 2018;13(3):e0195141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bashandy SAE, Ebaid H, Abdelmottaleb Moussa SA, Alhazza IM, Hassan I, Alaamer A, et al. Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on oxidative-mediated hepatotoxicity induced by thioacetamide. Lipids Health Dis. 2018;17(1):29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Amagon KI, Awodele O, Akindele AJ. Methionine and vitamin B-complex ameliorate antitubercular drugs-induced toxicity in exposed patients. Pharmacol Res Perspect. 2017;5(5):e00360.

    Article  CAS  PubMed Central  Google Scholar 

  15. Rausch CR, Paul S, Marx KR, Jabbour E, Pemmaraju N, Ferrajoli A, et al. L-carnitine and vitamin B complex for the treatment of Pegasparaginase-induced hyperbilirubinemia. Clin Lymphoma Myeloma Leuk. 2018;18(5):e191–5.

    Article  PubMed  Google Scholar 

  16. Pound MW, Townsend ML, Dimondi V, Wilson D, Drew RH. Overview of treatment options for invasive fungal infections. Med Mycol. 2011;49(6):561–80.

    CAS  PubMed  Google Scholar 

  17. Björnsson E, Davidsdottir L. The long-term follow-up after idiosyncratic drug-induced liver injury with jaundice. J Hepatol. 2009;50(3):511–7.

    Article  PubMed  Google Scholar 

  18. Gayam V, Khalid M, Dahal S, Garlapati P, Gill A. Hyperacute liver injury following intravenous FLZ: a rare case of dose-independent hepatotoxicity. J Fam Med Prim Care. 2018;7(2):451–4.

    Article  Google Scholar 

  19. Afzal M, Khan R, Kazmi I, Anwar F. Hepatoprotective potential of new steroid against carbon tetrachloride-induced hepatic injury. Mol Cell Biochem. 2013;378(1–2):275–81.

    Article  CAS  PubMed  Google Scholar 

  20. Fernández I, Peña A, Del Teso N, Pérez V, Rodríguez-Cuesta J. Clinical biochemistry parameters in C57BL/6J mice after blood collection from the submandibular vein and retroorbital plexus. J Am Assoc Lab Anim Sci. 2010;49(2):202–6.

    PubMed  PubMed Central  Google Scholar 

  21. Rezaei-Matehkolaei A, Khodavaisy S, Alshahni MM, Tamura T, Satoh K, Abastabar M, et al. In Vitro antifungal activity of novel Triazole Efinaconazole and five comparators against dermatophyte isolates. Antimicrob Agents Chemother. 2018;62(5).

  22. Khoza S, Moyo I, Ncube D. Comparative hepatotoxicity of FLZ, ketoconazole, Itraconazole, terbinafine, and Griseofulvin in rats. J Toxicol. 2017;2017(6746989):1–9.

    Article  CAS  Google Scholar 

  23. Kyriakidis I, Tragiannidis A, Munchen S, Groll AH. Clinical hepatotoxicity associated with antifungal agents. Expert Opin Drug Saf. 2017;16(2):149–65.

    CAS  PubMed  Google Scholar 

  24. Rosalki SB, Mcintyre N. Biochemical investigations in the management of liver disease. Oxford textbook of clinical hepatology. 2nd ed. New York: Oxford University Press; 1999. p. 503–21.

    Google Scholar 

  25. Drotman RB, Lawhorn GT. Serum enzymes are indicators of chemical induced liver damage. Drug Chem Toxicol. 1978;1:163–71.

    Article  CAS  PubMed  Google Scholar 

  26. Santiago RP, Vieira C, Adanho CSA, Santana SS, Guarda CC, Figueiredo CVB, et al. Laboratory and genetic biomarkers associated with cerebral blood flow velocity in hemoglobin SC disease. Dis Markers. 2017;2017:6359871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bulmer AC, Coombes JS, Blanchfield JT, Toth I, Fassett RG, Taylor SM. Bile pigment pharmacokinetics and absorption in the rat: therapeutic potential for enteral administration. Br J Pharmacol. 2011;164(7):1857–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Uysal HB, Dağlı B, Yılmaz M, Kahyaoğlu F, Gökçimen A, Ömürlü İK, et al. Biochemical and histological effects of thiamine pyrophosphate against acetaminophen-induced hepatotoxicity. Basic Clin Pharmacol Toxicol. 2016;118(1):70–6.

    Article  CAS  PubMed  Google Scholar 

  29. Sanches SC, Ramalho LN, Mendes-Braz M, Terra VA, Cecchini R, Augusto MJ, et al. Riboflavin (vitamin B-2) reduces hepatocellular injury following liver ischaemia and reperfusion in mice. Food Chem Toxicol. 2014;67:65–71.

    Article  CAS  PubMed  Google Scholar 

  30. Li J, Dou X, Li S, Zhang X, Zeng Y, Song Z. Nicotinamide ameliorates palmitate-induced ER stress in hepatocytes via cAMP/PKA/CREB pathway-dependent Sirt1 upregulation. Biochim Biophys Acta. 2015;1853(11 Pt A):2929–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under the grant no. G-389.130-38. The authors, therefore, acknowledge with thanks DSR for their technical and financial support.

The authors thank Kaleemuddin Mohammed, Ph.D. research scholar at our department for his assistance in performing experiments and drafting this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Fahad A. Al-Abbasi or Firoz Anwar.

Ethics declarations

Conflict of interest

The Authors declare that there is no conflict of interest.

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

Al-Abbasi, F.A., Sadath, S., Mushtaq, G. et al. Vitamin B combination reduces fluconazole toxicity in Wistar rats. DARU J Pharm Sci 27, 525–531 (2019). https://doi.org/10.1007/s40199-019-00252-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40199-019-00252-9

Keywords

Navigation