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The renoprotective effects of hesperidin on kidney injury induced by exposure to severe chronic dust storm particulate matter through inhibiting the Smads/TGF-β1 signaling in rat

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Abstract

Exposure to dust storm particulate matter (PM) is detrimental to kidney tissue. In this study, the impacts of chronic intake of dusty PM were explored as a major objective in a specified compartment to make a real-like dust storm (DS) model, and the role of hesperidin (HSP) as an antioxidant on kidney tissue was assessed in rats. Thirty-two male Wistar rats (200-220 g) were randomly allocated into 4 groups: CA+NS: (clean air and normal saline as a vehicle of HSP). Dusty PM and NS (DS+NS). HSP+ CA: rats received 200 mg/kg of HSP by gavage for 28 days, once daily in addition to exposure to clean air. HSP+DS: HSP plus DS. In DS groups, the animals were exposed to dust storms at a concentration of 5000-8000 μg/m3 in the chamber for 1 h daily, for 4 consecutive weeks, except Thursdays and Fridays. At the end of the experiment, the animals were sacrificed for biochemical, inflammatory, oxidative stress, molecular parameters, and histological evaluation. DS significantly enhanced blood urea nitrogen and creatinine, inflammatory (tumor necrosis factor-α, and interleukin-1β), and oxidative stress indexes. Likewise, a significant increase was seen in mRNA Smads, collagen-I, and transforming growth factor-β1 (TGF-β1) expressions in the kidney. Histological findings showed contracted glomeruli and kidney structure disorder. In addition, Masson’s trichrome staining demonstrated renal fibrosis. Nevertheless, HSP could significantly reverse these changes. Our data confirmed that DS results in kidney fibrosis through enhancing Smads/TGF-β1 signaling. However, HSP was able to inhibit these changes as confirmed by histological findings.

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Data availability

All data generated or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

DS:

dust storm

PM:

particulate matter

HSP:

hesperidin

TGF-β1:

transforming growth factor-β1

CKD:

Chronic kidney diseases

ROS:

reactive oxygen species

TNF-α:

tumor necrosis factor-α

IL-1β:

interleukin-1β

TAC:

total antioxidant capacity

MDA:

malondialdehyde

RNA:

ribonucleic acid

DNA:

deoxyribonucleic acid

BUN:

blood urea nitrogen

Cr:

creatinine

PBS:

phosphate-buffered saline

qRT-PCR:

quantitative real-time PCR

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

H&E:

hematoxylin/eosin

MTS:

Masson’s Trichrome staining

ANOVA:

one-way analysis of variance

SEM:

mean ± standard error

Bax:

Bcl-2 associated x protein

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Acknowledgements

The authors would like to express their gratitude for the assistance of the Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences.

Funding

This work was supported financially by the Persian Gulf Physiology Research Center (APRC-0017) funded by the Vice Chancellor of Research, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Alireza Sarkaki, Mohammad Badavi & Negin Amini

  2. Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Alireza Sarkaki, Mohammad Badavi, Somayeh Hajipour & Negin Amini

  3. Medicinal Plants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Alireza Sarkaki

  4. Cellular and molecular research center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Fereshteh Nejaddehbashi & Negin Amini

  5. Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

    Zahra Basir

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  1. Alireza Sarkaki
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Contributions

NA designed the study and wrote the manuscript. AS contributed to the technical advising and critical revision of the manuscript. MB performed the data analysis and interpreted the results. FN performed molecular analysis. SH contributed to the data collection. ZB performed the histology. All authors read and approved the final version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Negin Amini.

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The current research was confirmed by the Animal Ethics Committee of Ahvaz Junidshapur University of Medical Sciences, Iran (IR.AJUMS.ABHC.REC.1400.095).

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This is an animal study.

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Sarkaki, A., Badavi, M., Nejaddehbashi, F. et al. The renoprotective effects of hesperidin on kidney injury induced by exposure to severe chronic dust storm particulate matter through inhibiting the Smads/TGF-β1 signaling in rat. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3615–3626 (2023). https://doi.org/10.1007/s00210-023-02562-x

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