Combined effect of naringin and adipose tissue-derived mesenchymal stem cell on cisplatin nephrotoxicity through Sirtuin1/Nrf-2/HO-1 signaling pathway: a promising nephroprotective candidate

Negin Amini ^1,2, Fereshteh Nejaddehbashi ³, Mohammad Badavi ^4,5

⁰Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. negin.aminii@yahoo.com.

Cell and Tissue Research +

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July 2, 2024

View abstract on PubMed

Summary

Naringin and adipose tissue-derived mesenchymal stem cells (AD-MSCs) protect kidneys from cisplatin damage. Combining naringin with AD-MSCs offers superior renoprotection by reducing inflammation and oxidative stress.

Area Of Science

Nephrology
Pharmacology
Regenerative Medicine

Background

Cisplatin-induced nephrotoxicity is a severe clinical issue driven by oxidative stress and inflammation.
Naringin (NAR) exhibits antioxidant and renoprotective properties by scavenging reactive oxygen species.
Adipose tissue-derived mesenchymal stem cells (AD-MSCs) possess anti-inflammatory and antioxidant capabilities.

Purpose Of The Study

To investigate the renoprotective effects of naringin (NAR) and AD-MSCs, individually and in combination, against cisplatin-induced nephrotoxicity.
To elucidate the role of the SIRT-1/Nrf-2/HO-1 pathway in the protective mechanisms.

Main Methods

Five groups of male Sprague-Dawley rats were used: sham, cisplatin, NAR + cisplatin, AD-MSCs + cisplatin, and NAR + AD-MSCs + cisplatin.
Treatments included cisplatin administration (6.5 mg/kg, i.p.), naringin pretreatment (1 week, i.p.), and AD-MSC injection (1 × 10^6, tail vein).
Kidney function, inflammation, oxidative stress, gene expression (SIRT-1, Nrf-2, HO-1), and kidney histology were assessed.

Main Results

Cisplatin significantly elevated blood urea nitrogen, creatinine, inflammation, and oxidative stress markers.
Cisplatin treatment reduced the mRNA expression of SIRT-1, Nrf-2, and HO-1, alongside causing kidney structural damage.
Both NAR and AD-MSCs, particularly in combination, significantly reversed cisplatin-induced kidney dysfunction, inflammation, and oxidative stress, while upregulating the SIRT-1/Nrf-2/HO-1 pathway.

Conclusions

Combined administration of naringin and AD-MSCs demonstrates a synergistic renoprotective effect against cisplatin-induced nephrotoxicity.
The combination therapy effectively mitigates inflammation and oxidative stress, offering a promising therapeutic strategy.
The SIRT-1/Nrf-2/HO-1 pathway is a key mediator in the renoprotective actions of naringin and AD-MSCs.

Keywords:

Cisplatin Mesenchymal stem cells Naringin Nephrotoxicity

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