Zhou 2020 Biomed Pharmacother
|Zhou J, Zhang Y, Li S, Zhou Q, Lu Y, Shi J, Liu J, Wu Q, Zhou S (2020) Dendrobium nobile Lindl. alkaloids-mediated protection against CCl4-induced liver mitochondrial oxidative damage is dependent on the activation of Nrf2 signaling pathway. Biomed Pharmacother 129:110351.|
Abstract: The activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway has been involved in the mechanisms of a variety of protective agents against cellular oxidative stress. We recently demonstrated that Dendrobium nobile Lindl. alkaloids (DNLA), the active ingredients of Dendrobium, protects mice from CCl4-induced liver injury, dependent on the Nrf2 signaling pathway. The present study was aimed to determine whether the protection against mitochondrial oxidative damage plays a role in the mode of action of DNLA on CCl4-induced liver injury, and to further investigate whether the DNLA-conferred mitochondrial beneficial effects is dependent on the activation of Nrf2 signaling. The CCl4-induced acute liver injury model was employed in both wild-type (WT) and Nrf2-knockout (Nrf2−/−) mice. The results showed that in WT mice DNLA reduced CCl4-induced liver injury, accompanied by a significant reduction in CCl4-induced mitochondrial oxidative stress as evidenced by a decrease in mitochondrial H2O2 content and MDA production, and a marked increase in GSH level and Mn-SOD activity. However, these protective effects were significantly attenuated in Nrf2−/− mice. Furthermore, the administration of DNLA improved mitochondrial oxygen consumption, elevated ATP production, and decreased CCl4-induced apoptosis in the WT mice, whereas the DNLA-mediated protections on mitochondrial function were diminished in the Nrf2 null mice. These results demonstrate that the improvement of mitochondrial oxidative stress and mitochondrial dysfunction is implicated in the mechanism of DNLA-mediated protection on CCl4-induced liver injury, and this DNLA-modulated mode of action is dependent on the activation of Nrf2 signaling pathway.
Labels: MiParea: Respiration, Genetic knockout;overexpression
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS Pathway: N HRR: Oxygraph-2k