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Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice

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Abstract

Purpose

Cyclophosphamide is an alkylating agent with nephrotoxicity that constrains its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity.

Methods

Forty animal subjects were randomly separated into five categories of control (Group I), cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor-α (TNF-α) and interleukin 1 beta (IL-1β) levels as inflammatory mediators were assessed in kidney tissue.

Results

The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1β and increasing the level of GSH, CAT, SOD, and GPx activities.

Conclusion

Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

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Funding

This work was supported by Deputy of Research of Shoushtar University of Medical Sciences, Shoushtar, Iran (Grant number: TRC-9803) and Vice-Chancellor of Research, Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

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Authors and Affiliations

  1. Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Mohammad Amin Mombeini, Hadi Kalantar & Elahe Sadeghi

  2. Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Mehdi Goudarzi & Hamidreza Khalili

  3. Shoushtar Faculty of Medical Sciences, Shoushtar, Iran

    Mojtaba Kalantar

Authors
  1. Mohammad Amin Mombeini
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  2. Hadi Kalantar
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  3. Elahe Sadeghi
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  4. Mehdi Goudarzi
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  5. Hamidreza Khalili
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  6. Mojtaba Kalantar
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Contributions

MK and MAM conceived and designed the study. MAM, HK, and ES performed experiments. MAM, MG, and ES analyzed data. HK and HRK wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Mojtaba Kalantar.

Ethics declarations

Ethics approval

The investigation complies with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication no. 85–23, revised 1996). The investigation complies with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication no. 85–23, revised 1996). The Animal Ethics Committee of the Ahvaz Jundishapur University of Medical Sciences approved our research protocol (Ethic code: IR.BHN.REC.1397.033).

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The authors declare no competing interests.

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Mombeini, M.A., Kalantar, H., Sadeghi, E. et al. Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice. Naunyn-Schmiedeberg's Arch Pharmacol 395, 187–194 (2022). https://doi.org/10.1007/s00210-021-02182-3

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