The protective effect of a novel H2S donor Cys-S3 against liver injury in diabetic mice includes an antiferroptotic effect

Author : K. Velickovic, J. Stamenkovic, N. Savic, M. Markelic, A. Stancic, V. Otasevic

Abstract :Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, is involved in the development/progression of liver disease associated with diabetes. Although studies suggest that H2S protects cells from ferroptosis, it is unclear whether targeting ferroptosis through H2S signaling pathways could ameliorate diabetic liver injury. Therefore, T1D was induced with streptozotocin, and mice were treated with: GYY4137, the most studied slow-release H2S donor, the polysulfide donor Na2S4, and the in situ persulfide donor Cys-S3, or with liproxstatin-1 (Lip-1), an established ferroptosis inhibitor, for four weeks two months after the onset of T1D. H2S/RSS donors were found to improve biochemical parameters of glucose homeostasis, liver injury (ALT, AST) and histological indices (liver f ibrosis, hepatocyte size, binucleation). The increased lipid peroxidation caused by diabetes (indicated by the increased 4-HNE positivity and iron accumulation) was reduced by treatment with H2S/RSS donors. Decreased activation of Nrf2, GSH-related antioxidant defence parameters (GPX4, GCLC, GSS) and expression of iron sequestering proteins (ferritin, ferroportin) were improved/increased by H2S

Keywords :Diabetes, ferroptosis, H2S/RSS donors, liver.

Conference Name :International Conference on Environment and Life Science (ICELS-25)

Conference Place Vienna, Austria

Conference Date 17th Sep 2025