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• W4377029112 abstract "<b>Abstract ID 17232</b> <b>Poster Board 304</b> Cardiac involvement during sepsis frequently occurs, and considerable diabetes mellitus (DM) patients develop sepsis with concomitant cardiac complications. Propofol (PPF), one of the commonly used intravenous agents for anaesthesia and sedation, has been shown to have moderate antioxidant capacity that enables it to confer protection against cardiovascular complications that are associated with increases in oxidative stress when used at relatively high doses. However, application of propofol at high dose may cause hemodynamic instability especially in patients with pre-existing cardiovascular depressions such as sepsis and/or advanced stages of diabetes. Salvianolic acid A (SAA), a water-soluble extract of Danshen (Salvia miltiorrhiza Bunge), is a potent free radical scavenger that confers cardioprotection without noticeable cardiovascular side effects. PPF and SAA share partial structural similarity in terms of phenol structure. It is unknown whether or not PPF and SAA may confer synergistic cardioprotection in subjects with diabetes and sepsis. Rat heart-derived H9c2 cells were exposed to high glucose (HG) for 48 hours, then subjected to lipopolysaccharide (LPS) for 6 hours. HG+LPS significantly decreased cell viability, increased lactate dehydrogenase (LDH) leakage in H9c2 cells, all of which were significantly reversed by either PPF or SAA (respectively applied at 12.5, 25, and 50 μM) in a concentration-dependent manner. Administration of 12.5 μM PPF (P12.5) jointly with 12.5 μM SAA(S12.5) conferred superior protective effects to higher concentration of PPF alone at 25 μM (P25), manifested as significantly reduced productions of reactive oxygen species (ROS) and inflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-18, IL-1β and IL-6. Moreover, individual application of PPF or PPF and SAA in combination all significantly reduced HG+LPS-induced myocardial cell pyroptosis evidenced as reduced expression of NLRP3, ASC, caspase-1 and GSDMD (all<i> P</i><0.05, NC vs. HG; HG vs. HG+LPS; HG+LPS vs. HG+LPS+P25 or HG+LPS+P12.5+S12.5). Mechanistically, PPF and/or SAA mediated attenuation of H9c2 cells pyroptosis was associated with increased SIRT1 expression, and the protective effects were reversed by silencing SIRT1(all <i>P</i><0.05, HG+LPS+P25 or HG+LPS+P12.5+S12.5 vs. HG+LPS+P12.5+S12.5+siRNA). Taken together, these results indicated that PPF inhibits oxidative stress response of LPS-induced cardiomyocyte injury by targeting SIRT1 to inhibit NLRP3 dependent-pyroptosis under hyperglycemia and that SAA offers synergistic effect to PPF in cardiac protection, which may represent a novel therapeutic approach to avoid clinical side effects of high dose PPF." @default.
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• W4377029112 date "2023-05-18" @default.
• W4377029112 modified "2023-10-01" @default.
• W4377029112 title "Propofol and salvianolic acid A synergistically ameliorates LPS-induced H92 cells injury under hyperglycemia via enhancing SIRT1 to inhibit NLRP3 dependent-pyroptosis" @default.
• W4377029112 doi "https://doi.org/10.1124/jpet.122.172320" @default.
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