Ochronna rola CORMs w łagodzeniu stresu oksydacyjnego i stanu zapalnego indukowanego doksorubicyną w modelu prawidłowych komórek skóry - MINIATURA 8 2024/08/X/NZ7/01320 (dataset)

Abstract

Doxorubicin is a potent anticancer drug that unfortunately damages healthy cells. Researchers from the University of Łódź investigated whether carbon monoxide could protect against these side effects. They used CORMs (carbon monoxide-releasing molecules)—specifically CORM-2 and CORM-3—which safely deliver the gas to cells. The team tested these on healthy human fibroblasts exposed to doxorubicin, alongside inactive, gas-free molecules as a control. While pretreating cells with CORMs did not prevent the drug's overall toxicity, it effectively combated oxidative stress. Both CORM-2 and CORM-3 significantly reduced destructive oxygen free radicals induced by doxorubicin. Surprisingly, the inactive, gas-free molecules were equally effective at this. The researchers also assessed programmed cell death by measuring caspase activity. Active CORM-3 inhibited this process, showing a protective effect, whereas CORM-2 unexpectedly accelerated cell death. Additionally, CORM-3 reduced the activity of certain oxidative stress response genes without affecting inflammatory genes or final defensive protein levels. This research highlights the complex relationship between carbon monoxide releasers and chemotherapy. Although these molecules are not a cure-all for doxorubicin's toxicity, they possess valuable antioxidant properties. Crucially, the study reveals that the positive intracellular effects often stemmed from the molecule’s structural backbone itself rather than the released carbon monoxide. This discovery is a significant step toward understanding cellular mechanisms and designing better protective therapies for cancer patients.