β-Lapachone protects against doxorubicin-induced nephrotoxicity via NAD+/AMPK/NF-kB in mice

  • Davoud Sanajou
  • Saeed Nazari Soltan Ahmad
  • Vahid Hosseini
  • Ashkan Kalantary-Charvadeh
  • Yasser Marandi
  • Leila Roshangar
  • Saman Bahrambeigi
  • Mehran Mesgari-AbbasiEmail author
Original Article


β-Lapachone (B-LAP) is a natural naphtaquinone with established anti-oxidative stress and anti-cancer activities. We aimed to investigate B-LAP protective potential against doxorubicin (DOX)-induced nephrotoxicity in mice. The mice received an oral dose of B-LAP followed by a single intraperitoneal injection of 20 mg/kg DOX a day later. They were then treated for 4 days with 1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg doses of B-LAP. Renal levels of NAD+/NADH ratios, p-AMPKα, p-NF-κB p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) along with renal expressions of TNF-α, IL-1β, and IL-6 were examined. Serum levels of kidney function markers as well as renal histopathology were also investigated. In addition to increasing the activities of p-AMPKα, B-LAP elevated NAD+/NADH ratios in the kidneys and decreased the renal levels of nuclear p-NF-κB and its correspondent downstream effectors TNF-α, IL-1β, IL-6, and iNOS in the kidneys. Also, B-LAP effectively ameliorated renal architectural changes and attenuated serum levels of urea, creatinine, and cystatin C. Collectively, these findings suggest the protective actions of B-LAP against DOX-induced nephrotoxicity in mice.


β-Lapachone Doxorubicin NAD+/NADH ratio Nephrotoxicity 


Funding information

This work was supported with grants from the Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Compliance with ethical standards

The housing conditions and animal care procedures were set according to the protocols issued by the Tabriz University of Medical Sciences and approved by the Animal Ethics Council of the university.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Davoud Sanajou
    • 1
  • Saeed Nazari Soltan Ahmad
    • 1
  • Vahid Hosseini
    • 1
    • 2
  • Ashkan Kalantary-Charvadeh
    • 1
  • Yasser Marandi
    • 3
  • Leila Roshangar
    • 2
  • Saman Bahrambeigi
    • 4
  • Mehran Mesgari-Abbasi
    • 5
    Email author
  1. 1.Department of Biochemistry, Faculty of MedicineTabriz University of Medical SciencesTabrizIran
  2. 2.Stem Cell Research CenterTabriz University of Medical SciencesTabrizIran
  3. 3.Department of Biochemistry, Faculty of MedicineHamedan University of Medical SciencesHamedanIran
  4. 4.Department of Basic SciencesFaculty of Veterinary MedicineTabrizIran
  5. 5.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran

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