Effects of Landiolol in Lipopolysaccharide-Induced Acute Kidney Injury in Rats and In Vitro. Issue 5 (November 2019)

• Record Type: Journal Article
• Authors: Kiyonaga, Natsue; Moriyama, Takahiro; Kanmura, Yuichi
• Is Part Of: Shock. Volume 52:Issue 5(2019)
• Publication Date: 2019-11
• Subjects: Inflammation -- mitochondria -- oxidative stress -- oxygen consumption -- renal injury -- sepsis -- β-blocker; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000001306
• Languages: English
• ISSNs: 1073-2322

Abstract

Abstract : ABSTRACT: The mechanisms by which landiolol, an ultra-short-acting, selective β-1 blocker, could improve septic acute kidney injury and how inflammation might affect mitochondrial function and cause the renal injury were examined. Male Wistar rats (250 g–300 g) were randomly allocated to three groups: a sham control group (n = 8); a lipopolysaccharide (LPS) group (n = 8); and an LPS + landiolol group (n = 8). LPS was administered intravenously at the start of the experiments; the LPS + landiolol group rats received LPS and continuous intravenous landiolol. Serum creatinine and lactate concentrations and hemodynamic parameters were measured 3 and 6 h after the experiments started. TNF-α, IL-1β, and IL-6 levels and urinary 8-OHdG concentrations were determined. The extent of LPS-induced renal injury and recovery with landiolol were examined histopathologically. Metabolic analysis in human embryonic kidney cells was performed using Seahorse analysis. The effects of landiolol on cytokine-induced mitochondrial stress and glycolytic stress were examined. Treatment with landiolol was shown to normalize serum creatinine and lactate levels following intravenous LPS administration (Cr: LPS group 0.8 ± 0.6 mg/mL, LPS + landiolol group 0.5 ± 0.1 mg/mL; P < 0.05). In the in vitro experiments, TNF-α induced an increase in mitochondrial oxygen consumption, which was attenuated by landiolol, which could represent a mechanism for renal protection. Landiolol may have protective effects on the cells and tissues of the kidney by inhibiting oxygen consumption and hypoxia caused by TNF-α in renal cells. These results suggest that landiolol may be an important new therapeutic target for treating inflammation-associated kidney injury.