Genes & genomics · 2026
Cisplatin-induced oxidative stress and ferroptosis-associated injury in retinal pigment epithelial cells attenuated by Toxoplasma gondii infection.
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Wang Xin-Cheng, Yun Yu-Sun, Choi In-Wook, Zhou Wei, Yuk Jaemin, Cha Guang-Ho
Аннотация
BACKGROUND: Cisplatin causes oxidative and iron-dependent injury, but whether it induces ferroptosis-associated damage in retinal pigment epithelial cells and how Toxoplasma gondii (T. gondii) can modify this response remain unclear.
OBJECTIVE: This study investigated cisplatin-induced oxidative stress, apoptosis, ferroptosis-associated changes, and iron dysregulation in ARPE-19 cells and evaluated the effects of acute T. gondii infection.
METHODS: ARPE-19 cells were exposed to increasing concentrations of cisplatin for 24 h. Cell viability, oxidative stress, antioxidant capacity, apoptosis-related proteins, ferroptosis-defense molecules, and intracellular iron were assessed using biochemical assays, fluorescence staining, reverse-transcription polymerase chain reaction, and western blotting. Cells treated with 20 μM cisplatin were additionally infected with T. gondii at a multiplicity of infection of 5 or treated with ferrostatin-1, deferoxamine, or Z-VAD-FMK.
RESULTS: Cisplatin reduced cell viability in a concentration-dependent manner, with a half-maximal inhibitory concentration of 20.37 μM, and increased reactive oxygen species, malondialdehyde, cleaved caspase-3, and Bax while decreasing superoxide dismutase, glutathione, and Bcl-xL. It also reduced GPX4 and SLC7A11 protein expression and FSP1 mRNA levels, while increasing FTH1 and SLC11A2 protein expression and intracellular Fe2+ and total iron. T. gondii infection improved viability, reduced oxidative stress and cleaved caspase-3, restored antioxidant capacity and GPX4/SLC7A11 expression, and limited iron accumulation. Ferrostatin-1 and deferoxamine did not markedly suppress apoptotic proteins, whereas Z-VAD-FMK inhibited apoptotic signaling without restoring GPX4 or SLC7A11.
CONCLUSIONS: Cisplatin induces concurrent oxidative stress, apoptosis, impairment of ferroptotic defense, and iron accumulation in ARPE-19 cells. Acute T. gondii infection attenuates these alterations by preserving redox balance, ferroptosis-defense pathways, and iron homeostasis.
OBJECTIVE: This study investigated cisplatin-induced oxidative stress, apoptosis, ferroptosis-associated changes, and iron dysregulation in ARPE-19 cells and evaluated the effects of acute T. gondii infection.
METHODS: ARPE-19 cells were exposed to increasing concentrations of cisplatin for 24 h. Cell viability, oxidative stress, antioxidant capacity, apoptosis-related proteins, ferroptosis-defense molecules, and intracellular iron were assessed using biochemical assays, fluorescence staining, reverse-transcription polymerase chain reaction, and western blotting. Cells treated with 20 μM cisplatin were additionally infected with T. gondii at a multiplicity of infection of 5 or treated with ferrostatin-1, deferoxamine, or Z-VAD-FMK.
RESULTS: Cisplatin reduced cell viability in a concentration-dependent manner, with a half-maximal inhibitory concentration of 20.37 μM, and increased reactive oxygen species, malondialdehyde, cleaved caspase-3, and Bax while decreasing superoxide dismutase, glutathione, and Bcl-xL. It also reduced GPX4 and SLC7A11 protein expression and FSP1 mRNA levels, while increasing FTH1 and SLC11A2 protein expression and intracellular Fe2+ and total iron. T. gondii infection improved viability, reduced oxidative stress and cleaved caspase-3, restored antioxidant capacity and GPX4/SLC7A11 expression, and limited iron accumulation. Ferrostatin-1 and deferoxamine did not markedly suppress apoptotic proteins, whereas Z-VAD-FMK inhibited apoptotic signaling without restoring GPX4 or SLC7A11.
CONCLUSIONS: Cisplatin induces concurrent oxidative stress, apoptosis, impairment of ferroptotic defense, and iron accumulation in ARPE-19 cells. Acute T. gondii infection attenuates these alterations by preserving redox balance, ferroptosis-defense pathways, and iron homeostasis.