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

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 (NF_kB), 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, NF_kB, 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.