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Therapeutic effect of lycopene in lipopolysaccharide nephrotoxicity through alleviation of mitochondrial dysfunction, inflammation, and oxidative stress

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Abstract

Background

Sepsis-associated acute kidney injury (AKI) accompanies a higher mortality in intensive care patients. High-dose lipopolysaccharides (LPS) as an endotoxin is usually used to model AKI in rodents. Lycopene is a fat-soluble carotenoid with proved protective effects in different condition. Rationale and purpose of the study. This research work was designed to assess the effect of lycopene in LPS murine AKI.

Methods and results

LPS was injected (intraperitoneally) at 10 mg/kg to induce AKI and lycopene was given (orally) at 5 or 20 mg/kg. Pretreatment of LPS group with lycopene (20 mg/kg) lowered serum BUN, creatinine, and cystatin C and alleviated renal indices of oxidative stress consisting of malondialdehyde and reactive oxygen species and elevated level of catalase activity, superoxide dismutase activity, and glutathione peroxidase activity. In addition, lycopene (20 mg/kg) attenuated renal neutrophil infiltration and reduced renal inflammation, improved mitochondrial membrane potential, and increased gene expression for PGC1-α as a key regulator of mitochondrial biogenesis. In addition, lycopene appropriately reduced level and gene expression of inflammation-related transcription factors including NF-kB and TLR4 and improved level and gene expression of Nrf2 as an important transcription factor related to antioxidant system. Besides, lycopene prevented histopathological changes following LPS in periodic acid-Schiff staining.

Conclusions

Collectively, this study revealed that lycopene has favorable effects by means of amelioration of mitochondrial dysfunction, oxidative stress, and inflammation and accordingly could protect against LPS-induced AKI.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AKI:

Acute kidney injury

BUN:

Blood urea nitrogen

DCF-DA:

Dichlorofluorescein diacetate

ERK:

Extracellular signal-regulated kinase

FRAP:

Ferric reducing antioxidant power

GPX:

Glutathione peroxidase

HO-1:

Heme oxygenase 1

IFNγ:

Interferon gamma

IL-6:

Interleukin-6

JNK:

C-Jun N-terminal kinase

LPS:

Lipopolysaccharide

MDA:

Malondialdehyde

MAPK:

Mitogen-activated protein kinase

MMP:

Mitochondrial membrane potential

MPO:

Myeloperoxidase

NGAL:

Neutrophil gelatinase-associated lipocalin

NF-κB:

Nuclear factor-kappaB

Nrf2:

Nuclear factor erythroid-2-related factor 2

PAS:

Periodic acid-Schiff

PGC1-α:

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TBA:

2-Thiobarbituric acid

TLR4:

Toll-like receptor 4

TAC:

Total anti-oxidant capacity

t-BHP:

Tert-butyl hydroperoxide

TNFα:

Tumor necrosis factor α

TCA:

Trichloroacetic acid

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Funding

This research project was financially supported by a research Grant (no. 963250) from National Institute for Medical Research Development (NIMAD).

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Authors and Affiliations

  1. School of Medicine, Shahed University, Tehran, Iran

    Sepide Salari & Atefeh Ghorbanpour

  2. Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Narges Marefati

  3. Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Tourandokht Baluchnejadmojarad

  4. Neurophysiology Research Center, Shahed University, Tehran, Iran

    Mehrdad Roghani

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  1. Sepide Salari
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  2. Atefeh Ghorbanpour
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  3. Narges Marefati
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  5. Mehrdad Roghani
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Contributions

SS and AG performed the experiments, NM helped in writing the manuscript and data analysis, TB and MR supervised the study and reviewed the paper. All authors read and reviewed the final manuscript.

Corresponding author

Correspondence to Mehrdad Roghani.

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Conflict of interest

The authors hereby report no conflicts of interest. The authors take all responsible for the content and writing of this article.

Ethical approval

All procedures of this research study were in accordance to the Guide for the Care and Use of Laboratory Animals, set by the NIH and certified by National Institute for Medical Research Development (NIMAD) (no. IR.NIMAD.REC.1396.301).

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Salari, S., Ghorbanpour, A., Marefati, N. et al. Therapeutic effect of lycopene in lipopolysaccharide nephrotoxicity through alleviation of mitochondrial dysfunction, inflammation, and oxidative stress. Mol Biol Rep 49, 8429–8438 (2022). https://doi.org/10.1007/s11033-022-07661-1

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