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Effects of Landiolol in Lipopolysaccharide-Induced Acute Kidney Injury in Rats and In Vitro.
Kiyonaga, Natsue; Moriyama, Takahiro; Kanmura, Yuichi.
Affiliation
  • Kiyonaga N; Department of Anesthesiology and Intensive Care, Kagoshima University Hospital, Kagoshima, Japan.
Shock ; 52(5): e117-e123, 2019 11.
Article in En | MEDLINE | ID: mdl-30585987
ABSTRACT
The mechanisms by which landiolol, an ultra-short-acting, selective ß-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-1ß, 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 ±â€Š0.6 mg/mL, LPS + landiolol group 0.5 ±â€Š0.1 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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Urea / Lipopolysaccharides / Morpholines / Acute Kidney Injury Limits: Animals Language: En Journal: Shock Journal subject: ANGIOLOGIA / CARDIOLOGIA Year: 2019 Document type: Article Affiliation country: Japón

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Urea / Lipopolysaccharides / Morpholines / Acute Kidney Injury Limits: Animals Language: En Journal: Shock Journal subject: ANGIOLOGIA / CARDIOLOGIA Year: 2019 Document type: Article Affiliation country: Japón