| Abstract: | AIM：To investigate whether hydrogen sulfide (H2S) attenuates doxorubicin (DOX)-induced inflammation and cytotoxicity in rat cardiomyocytes (H9c2 cells) by modulating nuclear factor κB (NF-κB) pathway. METHODS：The expression of NF-κB p65 was measured by western blotting. The secretion levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNF-α) were tested by enzyme-linked immunosorbent assay (ELISA). Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Hoechst 33258 nuclear staining was used to detect the morphological changes and number of apoptotic cells. RESULTS：Treatment of H9c2 cells with 5 μmol/L DOX significantly up-regulated the expression level of phosphorylated NF-κB p65 (p-p65), and induced inflammation and cytotoxicity, as evidenced by increases in secretion levels of IL-1β, IL-6 and TNF-α and number of apoptotic cells as well as a decrease in cell viability. Pretreatment of H9c2 cells with 400 μmol/L NaHS (a donor of H2S) for 30 min markedly depressed the up-regulation of p-p65 expression induced by DOX. In addition, NaHS pretreatment also reduced DOX-induced inflammatory response and injury, leading to decreases in IL-1β, IL-6 and TNF-α secretion and number of apoptotic cells as well as an increase in cell viability. Similar to the effect of NaHS, pretreatment with 100 μmol/L pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, also blocked DOX-induced cardiac inflammation and cytotoxicity. Co-administration of IL-1 receptor antagonist (IL-1Ra) and DOX reduced DOX-induced activation of NF-κB and cytotoxicity in H9c2 cells. CONCLUSION：During the DOX-induced cardiomyocyte inflammation, there is positive interaction between NF-κB pathway and IL-1β. H2S may protect cardiomyocytes against DOX-induced inflammatory response and cytotoxicity by inhibiting NF-κB pathway. |
