Protodioscin mitigates cyclophosphamide-induced renal toxicity in HEK-293 cells by regulating endoplasmic reticulum stress, antioxidant defense, and apoptotic pathways
5 affiliations
- 1Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- 2Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- 3Department of Immunology, Factually of Medical Sciences, Tarbiat Modares University, Tehran, Iran
- 4Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
- 5Stem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Abstract
Cyclophosphamide (CTX) is a widely used chemotherapeutic agent with well-established efficacy; however, its clinical use is limited by dose-dependent adverse effects, particularly nephrotoxicity. Protodioscin (Prot), a bioactive saponin derived from plants of the Dioscoreaceae family, has demonstrated notable antioxidant and anti-inflammatory properties. This study aimed to evaluate the protective effects of Prot against CTX-induced cytotoxicity in HEK-293 cells. Primary HEK-293 kidney cells were exposed to the IC50 concentration of CTX in the presence or absence of Prot (5 and 10 µM) for 24 hours. Cell viability was assessed using the MTT assay. Gene expression of Bax and Bcl-2 was measured by real-time PCR assay, while protein expression of Bax, cleaved caspase-3, Bcl-2, ATF6, PERK, GRP78, CHOP, p-eIF2α, p-PERK, and cleaved ATF6 were evaluated by Western blot analysis. Oxidative stress parameters, including CAT, SOD, GPx, GSH, MDA, and NO, were quantified using spectrophotometric assays, and kidney injury markers (KIM-1 and cystatin C) were measured by ELISA. Prot decreased Bax and caspase 3 expression and increased Bcl-2 expression in HEK-293 cells exposed to CTX, which was accompanied by reduced apoptosis. Treatment with 5 and 10 µM Prot significantly reduced the expression of ATF6, PERK, GRP78, CHOP, p-eIF2α, p-PERK and Cleaved- ATF6 proteins in CTX-exposed HEK-293 cells. Additionally, treatment with Prot significantly increased catalase, GPx, GSH, and SOD levels, while reducing KIM-1, cystatin C, MDA, and NO levels in HEK-293 cells subjected to CTX. These findings suggest that Prot exerts a protective role against CTX-induced renal injury in HEK-293 cells by modulating apoptotic pathways, attenuating endoplasmic reticulum stress, and improving antioxidant indices.
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BibTeX
@article{ahmadi2026protodioscin,
title = {{Protodioscin mitigates cyclophosphamide-induced renal toxicity in HEK-293 cells by regulating endoplasmic reticulum stress, antioxidant defense, and apoptotic pathways}},
author = {Ahmad Reza Ahmadi and Touraj Zamir Nasta and Ardeshir Abbasi and Mohammad Reza Tabandeh and Cyrus Jalili},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357227},
url = {https://doi.org/10.1371/journal.pone.0357227},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Protodioscin mitigates cyclophosphamide-induced renal toxicity in HEK-293 cells by regulating endoplasmic reticulum stress, antioxidant defense, and apoptotic pathways
AU - Ahmad Reza Ahmadi
AU - Touraj Zamir Nasta
AU - Ardeshir Abbasi
AU - Mohammad Reza Tabandeh
AU - Cyrus Jalili
PY - 2026
DA - 2026/09/21
JO - PLOS One
DO - 10.1371/journal.pone.0357227
UR - https://doi.org/10.1371/journal.pone.0357227
AB - Cyclophosphamide (CTX) is a widely used chemotherapeutic agent with well-established efficacy; however, its clinical use is limited by dose-dependent adverse effects, particularly nephrotoxicity. Protodioscin (Prot), a bioactive saponin derived from plants of the Dioscoreaceae family, has demonstrated notable antioxidant and anti-inflammatory properties. This study aimed to evaluate the protective effects of Prot against CTX-induced cytotoxicity in HEK-293 cells. Primary HEK-293 kidney cells were exposed to the IC50 concentration of CTX in the presence or absence of Prot (5 and 10 µM) for 24 hours. Cell viability was assessed using the MTT assay. Gene expression of Bax and Bcl-2 was measured by real-time PCR assay, while protein expression of Bax, cleaved caspase-3, Bcl-2, ATF6, PERK, GRP78, CHOP, p-eIF2α, p-PERK, and cleaved ATF6 were evaluated by Western blot analysis. Oxidative stress parameters, including CAT, SOD, GPx, GSH, MDA, and NO, were quantified using spectrophotometric assays, and kidney injury markers (KIM-1 and cystatin C) were measured by ELISA. Prot decreased Bax and caspase 3 expression and increased Bcl-2 expression in HEK-293 cells exposed to CTX, which was accompanied by reduced apoptosis. Treatment with 5 and 10 µM Prot significantly reduced the expression of ATF6, PERK, GRP78, CHOP, p-eIF2α, p-PERK and Cleaved- ATF6 proteins in CTX-exposed HEK-293 cells. Additionally, treatment with Prot significantly increased catalase, GPx, GSH, and SOD levels, while reducing KIM-1, cystatin C, MDA, and NO levels in HEK-293 cells subjected to CTX. These findings suggest that Prot exerts a protective role against CTX-induced renal injury in HEK-293 cells by modulating apoptotic pathways, attenuating endoplasmic reticulum stress, and improving antioxidant indices.
SN - 1932-6203
ER -