“Radiation-Synthesized Gallotannin Hydrogel Attenuates Trisenox-Induced Nephrotoxicity in Rats: miR-223/TXNIP Axis Modulation of Oxidative Stress and Inflammation”
- 1Biochemistry and Molecular Biology Department, Faculty of veterinary Medicine, Benha University, Benha, Egypt
- 2Radiation Biology Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt
- 3Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
Abstract
Arsenic trioxide (ATO) is a potent therapeutic agent against acute promyelocytic leukemia; nevertheless, its clinical utility is severely restricted by dose-limiting nephrotoxicity. This study investigated the protective potential of a radiation-synthesized gallotannin hydrogel (GTH) against ATO-induced kidney injury in rats. Forty male Wistar rats were randomized into four experimental groups: Control, ATO (4 mg/kg, i.p., for 4 weeks), GTH (2 mg/kg, i.p.), and ATO + GTH. GTH treatment was initiated during the third week of ATO administration, with GTH being administrated one hour prior to ATO injection. Following the experimental period, animals were sacrificed, tissue histology was examined, and renal function was assessed by serum urea and creatinine levels. Oxidative stress was evaluated via MDA, SOD, GSH, and GPx markers. Additionally, miR-223 and TXNIP expression levels were quantified using qRT-PCR. Inflammatory mediators (NF-κB, NLRP3, Caspase-1, IL-1β, and IL-18), endoplasmic reticulum (ER) stress markers (PERK, eIF2α, and CHOP), and the apoptotic marker caspase-3 were analyzed by ELISA. Our results revealed that GTH noticeably ameliorated kidney dysfunction, as evidenced by reduced serum urea and creatinine levels. Furthermore, GTH attenuated oxidative stress by decreasing MDA levels and restoring antioxidant enzyme activities (SOD, GSH, and GPx). Histological analysis confirmed that GTH mitigated structural renal damage. Molecularly, GTH administration suppressed the ATO-induced upregulation of miR-223 and TXNIP. This downregulation correlated with a reduction in inflammatory mediators, attenuation of ER stress markers, and decreased apoptosis. These findings demonstrate that radiation-synthesized gallotannin hydrogel (GTH) exerts nephroprotective effects against ATO-induced nephrotoxicity. These benefits are driven by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms mediated via modulation of the miR-223/TXNIP axis.
Graphical Abstract:
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BibTeX
@article{abozaid2026radiationsynthesized,
title = {{“Radiation-Synthesized Gallotannin Hydrogel Attenuates Trisenox-Induced Nephrotoxicity in Rats: miR-223/TXNIP Axis Modulation of Oxidative Stress and Inflammation”}},
author = {Omayma A.R. Abo-Zaid and Mostafa A. Farrag and Aya S. R. Shaaban and Hiam Rushdy A Salem and Marwa A. Esmat},
journal = {Biological Trace Element Research},
year = {2026},
month = sep,
doi = {10.1007/s12011-026-05301-4},
url = {https://doi.org/10.1007/s12011-026-05301-4},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - “Radiation-Synthesized Gallotannin Hydrogel Attenuates Trisenox-Induced Nephrotoxicity in Rats: miR-223/TXNIP Axis Modulation of Oxidative Stress and Inflammation”
AU - Omayma A.R. Abo-Zaid
AU - Mostafa A. Farrag
AU - Aya S. R. Shaaban
AU - Hiam Rushdy A Salem
AU - Marwa A. Esmat
PY - 2026
DA - 2026/09/04
JO - Biological Trace Element Research
DO - 10.1007/s12011-026-05301-4
UR - https://doi.org/10.1007/s12011-026-05301-4
AB - Arsenic trioxide (ATO) is a potent therapeutic agent against acute promyelocytic leukemia; nevertheless, its clinical utility is severely restricted by dose-limiting nephrotoxicity. This study investigated the protective potential of a radiation-synthesized gallotannin hydrogel (GTH) against ATO-induced kidney injury in rats. Forty male Wistar rats were randomized into four experimental groups: Control, ATO (4 mg/kg, i.p., for 4 weeks), GTH (2 mg/kg, i.p.), and ATO + GTH. GTH treatment was initiated during the third week of ATO administration, with GTH being administrated one hour prior to ATO injection. Following the experimental period, animals were sacrificed, tissue histology was examined, and renal function was assessed by serum urea and creatinine levels. Oxidative stress was evaluated via MDA, SOD, GSH, and GPx markers. Additionally, miR-223 and TXNIP expression levels were quantified using qRT-PCR. Inflammatory mediators (NF-κB, NLRP3, Caspase-1, IL-1β, and IL-18), endoplasmic reticulum (ER) stress markers (PERK, eIF2α, and CHOP), and the apoptotic marker caspase-3 were analyzed by ELISA. Our results revealed that GTH noticeably ameliorated kidney dysfunction, as evidenced by reduced serum urea and creatinine levels. Furthermore, GTH attenuated oxidative stress by decreasing MDA levels and restoring antioxidant enzyme activities (SOD, GSH, and GPx). Histological analysis confirmed that GTH mitigated structural renal damage. Molecularly, GTH administration suppressed the ATO-induced upregulation of miR-223 and TXNIP. This downregulation correlated with a reduction in inflammatory mediators, attenuation of ER stress markers, and decreased apoptosis. These findings demonstrate that radiation-synthesized gallotannin hydrogel (GTH) exerts nephroprotective effects against ATO-induced nephrotoxicity. These benefits are driven by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms mediated via modulation of the miR-223/TXNIP axis. Graphical Abstract:
SN - 0163-4984
SN - 1559-0720
ER -