Cisplatin-induced oxidative stress and ferroptosis-associated injury in retinal pigment epithelial cells attenuated by Toxoplasma gondii infection.

backgroundCisplatin 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.

objectiveThis 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.

methodsARPE-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.

resultsCisplatin 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 Fe

conclusionsCisplatin 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.