Dexpanthenol Attenuates Methotrexate-Induced Nephrotoxicity Through Modulation of NF-κB-Mediated Inflammation and SIRT1/PGC-1α-NRF2/HO-1-Associated Oxidative Stress Pathways.

Authors

Atila Altuntas, Halil Asci, Esma Selcuk, Huzeyfe Karaosman, Osman Aydin, Ilter Ilhan, Sefa Alperen Ozturk, Ozlem Ozmen

Published in

Journal of biochemical and molecular toxicology. Volume 40. Issue 8. Pages e71055.

Abstract

Methotrexate (MTX)-induced nephrotoxicity remains a clinically relevant limitation associated with oxidative stress, inflammation, and apoptosis. Dexpanthenol (DEX), a pantothenic acid derivative, has demonstrated cytoprotective properties; however, its effects on MTX-induced renal injury and related molecular pathways are not fully elucidated. This study investigated the potential renoprotective effects of DEX with a focus on inflammation- and redox-associated signaling. Thirty-two male Wistar rats were allocated into four groups: Control, MTX, MTX + DEX, and DEX. Renal injury was assessed by histopathology, immunohistochemical analysis of caspase-3, NF-κB, and TNF-α, biochemical parameters (urea and creatinine), and RT-qPCR analysis of SIRT1, PGC-1α, NRF2, and HO-1 gene expression. MTX administration resulted in marked renal damage characterized by tubular degeneration, hyperemia, and inflammatory infiltration, accompanied by increased caspase-3, NF-κB, and TNF-α expression (p < 0.001). MTX also significantly suppressed SIRT1, PGC-1α, NRF2, and HO-1 gene expression (p < 0.001). DEX co-treatment attenuated histopathological injury and significantly reduced pro-inflammatory and apoptotic markers while restoring SIRT1, PGC-1α, and HO-1 expression (p < 0.01-0.001), with a non-significant upward trend in NRF2 levels. Biochemically, DEX reduced MTX-induced urea and creatinine elevation. DEX confers significant protection against MTX-induced renal injury, likely through modulation of inflammatory and oxidative stress-related regulatory pathways and attenuation of apoptosis. These findings support the potential of DEX as a pharmacological candidate for mitigating drug-induced nephrotoxicity; however, further studies at the protein and functional levels are warranted.

PMID:
42546171
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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