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Distinct concentration-dependent oxidative stress profiles by cadmium in a rat kidney proximal tubule cell line

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Názov: Distinct concentration-dependent oxidative stress profiles by cadmium in a rat kidney proximal tubule cell line
Autori: Wing-Kee Lee, Stephanie Probst, Bettina Scharner, Timo Deba, Faouzi Dahdouh, Frank Thévenod
Zdroj: Arch Toxicol
Informácie o vydavateľovi: Springer Science and Business Media LLC, 2024.
Rok vydania: 2024
Predmety: 0301 basic medicine, 0303 health sciences, Superoxide Dismutase, Metalloporphyrins, alpha-Tocopherol, Superoxide Dismutase-1/pharmacology [MeSH], Cell Line [MeSH], Oxidative Stress [MeSH], Cadmium/toxicity [MeSH], Spin Labels [MeSH], Superoxides/metabolism [MeSH], Inorganic Compounds, Catalase/pharmacology [MeSH], Superoxide, Antioxidants/metabolism [MeSH], alpha-Tocopherol/metabolism [MeSH], Antioxidants/pharmacology [MeSH], Hydrogen Peroxide/metabolism [MeSH], Redox, Hydrogen peroxide, Catalase, Reactive Oxygen Species/metabolism [MeSH], Rats [MeSH], Kidney [MeSH], Animals [MeSH], alpha-Tocopherol/pharmacology [MeSH], Metalloporphyrins [MeSH], Reactive oxygen species, Cyclic N-Oxides [MeSH], Superoxide Dismutase-1/metabolism [MeSH], Superoxide Dismutase/metabolism [MeSH], Catalase/metabolism [MeSH], Hydrogen Peroxide, Kidney, Antioxidants, Rats, Cell Line, Cyclic N-Oxides, Oxidative Stress, 03 medical and health sciences, Superoxide Dismutase-1, Superoxides, Animals, Spin Labels, Reactive Oxygen Species, Cadmium
Popis: Levels and chemical species of reactive oxygen/nitrogen species (ROS/RNS) determine oxidative eustress and distress. Abundance of uptake pathways and high oxygen consumption for ATP-dependent transport makes the renal proximal tubule particularly susceptible to cadmium (Cd2+)-induced oxidative stress by targeting ROS/RNS generation or antioxidant defence mechanisms, such as superoxide dismutase (SOD) or H2O2-metabolizing catalase (CAT). Though ROS/RNS are well-evidenced, the role of distinct ROS profiles in Cd2+ concentration-dependent toxicity is not clear. In renal cells, Cd2+ (10–50 µM) oxidized dihydrorhodamine 123, reaching a maximum at 2–3 h. Increases (up to fourfold) in lipid peroxidation by TBARS assay and H2O2 by Amplex Red were evident within 30 min. ROS and loss in cell viability by MTT assay with 50 µM Cd2+ could not be fully reversed by SOD mimetics Tempol and MnTBAP nor by SOD1 overexpression, whereas CAT expression and α-tocopherol were effective. SOD and CAT activities were attenuated below controls only with >6 h 50 µM Cd2+, yet augmented by up to 1.5- and 1.2-fold, respectively, by 10 µM Cd2+. Moreover, 10 µM, but not 25–50 µM Cd2+, caused 1.7-fold increase in superoxide anion (O2•−), detected by dihydroethidium, paralled by loss in cell viability, that was abolished by Tempol, MnTBAP, α-tocopherol and SOD1 or CAT overexpression. H2O2-generating NADPH oxidase 4 (NOX4) was attenuated by ~50% with 10 µM Cd2+ at 3 h compared to upregulation by 50 µM Cd2+ (~1.4-fold, 30 min), which was sustained for 24 h. In summary, O2•− predominates with low–moderate Cd2+, driving an adaptive response, whereas oxidative stress by elevated H2O2 at high Cd2+ triggers cell death signaling pathways.Highlights Different levels of reactive oxygen species are generated, depending on cadmium concentration. Superoxide anion predominates and H2O2 is suppressed with low cadmium representing oxidative eustress. High cadmium fosters H2O2 by inhibiting catalase and increasing NOX4 leading to oxidative distress. Superoxide dismutase mimetics and overexpression were less effective with high versus low cadmium. Oxidative stress profile could dictate downstream signalling pathways.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1432-0738
0340-5761
DOI: 10.1007/s00204-023-03677-z
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38289529
https://repository.publisso.de/resource/frl:6499561
Rights: CC BY
"In Copyright" Rights Statement
Prístupové číslo: edsair.doi.dedup.....5e31eaa0f9cdd483fc87870e2a7f92c6
Databáza: OpenAIRE
Popis
Abstrakt:Levels and chemical species of reactive oxygen/nitrogen species (ROS/RNS) determine oxidative eustress and distress. Abundance of uptake pathways and high oxygen consumption for ATP-dependent transport makes the renal proximal tubule particularly susceptible to cadmium (Cd2+)-induced oxidative stress by targeting ROS/RNS generation or antioxidant defence mechanisms, such as superoxide dismutase (SOD) or H2O2-metabolizing catalase (CAT). Though ROS/RNS are well-evidenced, the role of distinct ROS profiles in Cd2+ concentration-dependent toxicity is not clear. In renal cells, Cd2+ (10–50 µM) oxidized dihydrorhodamine 123, reaching a maximum at 2–3 h. Increases (up to fourfold) in lipid peroxidation by TBARS assay and H2O2 by Amplex Red were evident within 30 min. ROS and loss in cell viability by MTT assay with 50 µM Cd2+ could not be fully reversed by SOD mimetics Tempol and MnTBAP nor by SOD1 overexpression, whereas CAT expression and α-tocopherol were effective. SOD and CAT activities were attenuated below controls only with >6 h 50 µM Cd2+, yet augmented by up to 1.5- and 1.2-fold, respectively, by 10 µM Cd2+. Moreover, 10 µM, but not 25–50 µM Cd2+, caused 1.7-fold increase in superoxide anion (O2•−), detected by dihydroethidium, paralled by loss in cell viability, that was abolished by Tempol, MnTBAP, α-tocopherol and SOD1 or CAT overexpression. H2O2-generating NADPH oxidase 4 (NOX4) was attenuated by ~50% with 10 µM Cd2+ at 3 h compared to upregulation by 50 µM Cd2+ (~1.4-fold, 30 min), which was sustained for 24 h. In summary, O2•− predominates with low–moderate Cd2+, driving an adaptive response, whereas oxidative stress by elevated H2O2 at high Cd2+ triggers cell death signaling pathways.Highlights Different levels of reactive oxygen species are generated, depending on cadmium concentration. Superoxide anion predominates and H2O2 is suppressed with low cadmium representing oxidative eustress. High cadmium fosters H2O2 by inhibiting catalase and increasing NOX4 leading to oxidative distress. Superoxide dismutase mimetics and overexpression were less effective with high versus low cadmium. Oxidative stress profile could dictate downstream signalling pathways.
ISSN:14320738
03405761
DOI:10.1007/s00204-023-03677-z