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image of Naringin Alleviates Digoxin-induced Nephrotoxicity via Regulating Nrf2/ HO-1 and PI3K/ AKT/TGF-β Cascades in Rats’ Renal Tissues

Abstract

Background

Nephrotoxicity limits the clinical application of digoxin. One area that might be useful is the mechanical knowledge of altered renal function and renal impairment. We hypothesized that co-administration of naringin would affect digoxin nephrotoxicity by alleviating the altered renal oxidative/ antioxidant redox and apoptotic cascade.

Method

40 male Wistar Albino rats (200 ± 50 g) were grouped into 4, every group included (n= 7), control, Nar., Dig. and Nar. + dig. Groups. Colorimetric estimation of kidney functions and renal oxidative/ antioxidant redox were done.

Results

Comparing digoxin alone, the concomitant administration of digoxin and naringin restored renal antioxidant/ oxidative redox, redistributed Nrf2, HO-1 mRNA exposure with a concomitant down-regulation of NF-κB, AKT and PI3K mRNA expressions. Moreover, a significant decrease of Smad3 and transforming growth factor- (TGF- β) protein concentrations with a simultaneous rise of Smad7 were noticed in Nar. + dig. Arm when compared to Dig. group.

Conclusion

The co-administration of naringin and digoxin can mitigate digoxin-mediated nephrotoxicity by introducing antioxidant action. This is done by maintaining effects on renal oxidative/antioxidant cycle and lethality via regulating AKT/ PI3k/ Smad3/ Smad7 signaling pathways.

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2025-05-20
2025-09-19

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/content/journals/cpb/10.2174/0113892010340746250421065424
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Naringin Alleviates Digoxin-induced Nephrotoxicity via Regulating Nrf2/ HO-1 and PI3K/ AKT/TGF-β Cascades in Rats’ Renal Tissues
Bentham Science Publishers ; https://doi.org/10.2174/0113892010340746250421065424
/content/journals/cpb/10.2174/0113892010340746250421065424
/content/journals/cpb/10.2174/0113892010340746250421065424
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  • Article Type:     Research Article
Keywords: digoxin ; western plot ; apoptotic cascade ; nephrotoxicity ; Naringenin

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