Effects of Landiolol in Lipopolysaccharide-Induced Acute Kidney Injury in Rats and In Vitro.
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-300âg) were randomly allocated to three groups a sham control group (nâ=â8); a lipopolysaccharide (LPS) group (nâ=â8); and an LPSâ+âlandiolol group (nâ=â8). LPS was administered intravenously at the start of the experiments; the LPSâ+âlandiolol group rats received LPS and continuous intravenous landiolol. Serum creatinine and lactate concentrations and hemodynamic parameters were measured 3 and 6âh 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 0.8â±â0.6âmg/mL, LPSâ+âlandiolol group 0.5â±â0.1âmg/mL; Pâ<â0.05). 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.
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