# Investigation of the molecular and cellular effects of Shilajit on 5-fluorouracil (5-FU)-induced nephrotoxicity in rats

**Authors:** Mehmet Ezer, Melek Öztürkler, Kezban Yıldız-Dalgınlı, Emine Atakişi, Hatice Beşeren - Havadar, Onur Atakişi

PMC · DOI: 10.22038/ijbms.2025.80989.17525 · Iranian Journal of Basic Medical Sciences · 2025-01-01

## TL;DR

This study shows that shilajit can protect rat kidneys from damage caused by a chemotherapy drug called 5-fluorouracil.

## Contribution

The novel finding is that shilajit reduces 5-FU-induced nephrotoxicity through antioxidant and molecular pathways.

## Key findings

- Shilajit reduced oxidative stress and improved antioxidant status in rats treated with 5-FU.
- Shilajit increased the expression of SIRT2, SIRT3, and cell adhesion proteins in kidney tissues.
- Histopathological analysis showed less kidney damage in rats co-treated with shilajit and 5-FU.

## Abstract

This study aimed to evaluate the protective effects of shilajit on 5-fluorouracil (5-FU)-induced nephrotoxicity in a rat model.

Twenty male Sprague Dawley rats were divided into four groups: Control, 5-FU, shilajit, and 5-FU + shilajit. 5-FU was administered intraperitoneally at 200 mg/kg, while shilajit was given orally at 200 mg/kg. Kidney tissues were analyzed for oxidative stress markers, protein expression (SIRT2, SIRT3, β-catenin, E-cadherin, and caspase-3), and histopathological changes.

5-FU significantly increased oxidative stress parameters and kidney damage markers. Shilajit co-administration with 5-FU reduced oxidative stress and increased anti-oxidant status and SIRT2, SIRT3, and cell adhesion protein expression. Histopathological evaluation showed reduced renal damage in the shilajit + 5-FU group compared to the 5-FU group.

Shilajit exhibited significant protective effects against 5-FU-induced nephrotoxicity, improving oxidative parameters, protein expression, and kidney histopathology. Further studies are needed to elucidate its molecular mechanism and therapeutic potential.

## Linked entities

- **Genes:** SIRT2 (sirtuin 2) [NCBI Gene 22933], SIRT3 (sirtuin 3) [NCBI Gene 23410], ctnnb1.S (catenin beta 1 S homeolog) [NCBI Gene 380441], shg (shotgun) [NCBI Gene 37386], Casp3 (caspase 3) [NCBI Gene 12367]
- **Proteins:** SIRT2 (sirtuin 2), SIRT3 (sirtuin 3), ctnnb1.S (catenin beta 1 S homeolog), shg (shotgun), Casp3 (caspase 3)
- **Chemicals:** 5-fluorouracil (PubChem CID 3385)

## Full-text entities

- **Genes:** Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Sirt3 (sirtuin 3) [NCBI Gene 293615], Cdh1 (cadherin 1) [NCBI Gene 83502], Ctnnb1 (catenin beta 1) [NCBI Gene 84353] {aka Catnb}, Sirt2 (sirtuin 2) [NCBI Gene 361532]
- **Diseases:** kidney damage (MESH:D007674)
- **Chemicals:** Shilajit (MESH:C045109), 5-FU (MESH:D005472)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12258796/full.md

## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12258796/full.md

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Source: https://tomesphere.com/paper/PMC12258796