# Nephroprotective Impacts of Hyphaene thebaica (Doum) Against Gentamicin‐Induced Renal Toxicity Through Different Signaling Pathways

## TL;DR

Hyphaene thebaica extract protects against kidney damage caused by gentamicin by reducing inflammation and oxidative stress.

## Contribution

This study demonstrates the nephroprotective effects of Hyphaene thebaica through modulation of multiple signaling pathways in gentamicin-induced toxicity.

## Key findings

- Hyphaene thebaica reduced gentamicin-induced increases in creatinine, uric acid, and urea levels.
- The extract normalized gene expression of TGF-β1, NFkB, and TNF-α, and improved oxidative stress markers like Nrf2.
- Histopathological improvements were observed in the protective group treated with Hyphaene thebaica.

## Abstract

Hayphaene thebaica (
H. thebaica
) is thought to be effective in treating several diseases and has possible anti‐toxic impacts. Gentamycin (GM) toxicity in internal organs is mostly induced by oxidative stress production. Therefore, the current study aimed to examine the protective effect of
H. thebaica
) against gentamycin‐induced renal toxicity. Twenty‐four male mice were allocated into four groups: first group administered saline orally as a control, the second group administered
H. thebaica
extract (5%) for 2 weeks, third group injected intraperitoneally with GM (100 mg/kg, daily) for 15 days, and fourth group served as the protective one, receiving doses used in second and third groups for 2 weeks. To examine kidney function, serum was extracted. Renal tissues were collected and examined for gene expression, histopathology, and immunohistochemistry for nuclear factor kappa B (NFkB), transforming growth factor beta‐1 (TGF‐β1), and tumor necrosis factor‐alpha (TNF‐α) immunoreactivity. Serum levels of creatinine, uric acid, and urea were all increased after gentamicin injection. TGF‐β1 and cyclooxygenase‐2 (COX2) were upregulated in renal tissues of the gentamycin group compared to the control and
H. thebaica
groups using real‐time quantitative PCR (RT‐qPCR) analysis, unlike genes of oxidative stress markers, nuclear factor erythroid 2‐related factor 2 (Nrf2) was downregulated and was ameliorated by
H. thebaica
pre‐administration. Immunoreactivity of genes of TGF‐β1, NFkB, and TNF‐α was significantly immunoreacted and expressed in GM‐injected mice and was normalized and ameliorated in the protective group. There were deformities in renal histology represented by degenerative changes in the renal glomerulus, which was surrounded by a wide capsular space, degeneration in the tubular epithelium, and an increase in the accumulation of acidophilic proteinaceous substances within the lumens of some tubules in the gentamycin‐injected group compared to the protective group. These deformities were ameliorated by
Hyphaene thebaica
administration in the protective group.

Hyphaene thebaica
extract ameliorated nephrotoxic effects of gentamycin through its role as anti‐inflammatory mediators by regulating NFkB, COX‐2, and TGF‐β1 expressions. Moreover,
H. thebaica
regulated the expression of inflammation‐associated apoptotic genes.
H. thebaica
increased antioxidative stress biomarkers named Nrf2, catalase, and GSH. Therefore, using
H. thebaica
as a supplemental nutrient against toxicity of the kidney is acceptable with limitation to its possible impacts for use in medication.