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Effects of dexmedetomidine on lipopolysaccharide-induced acute kidney injury in rats and mitochondrial function in cell culture.
Kiyonaga, Natsue; Moriyama, Takahiro; Kanmura, Yuichi.
Affiliation
  • Kiyonaga N; Department of Anesthesiology and Intensive Care, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima Prefecture, 890-0075, Japan.
  • Moriyama T; Department of Anesthesiology and Intensive Care, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima Prefecture, 890-0075, Japan. Electronic address: takmor@m3.kufm.kagoshima-u.ac.jp.
  • Kanmura Y; Department of Anesthesiology and Intensive Care, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima Prefecture, 890-0075, Japan.
Biomed Pharmacother ; 125: 109912, 2020 May.
Article in En | MEDLINE | ID: mdl-32014689
ABSTRACT

PURPOSE:

To investigate the mechanisms through which dexmedetomidine (DEX) could improve the renal injury in lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and examine how TNF-α or DEX might affect mitochondrial function and renal injury.

METHODS:

In vivo experiments involved 24 rats randomly allocated to a sham group, an LPS group, and an LPS + DEX group. Serum creatinine, lactate, TNF-α, IL-1ß, and IL-6 concentrations, as well as urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, were measured 0, 3, and 6 h after the start of the experiments. Histopathological examinations were performed to determine the extent of LPS-induced renal injury and recovery by administration of DEX. in vitro, human embryonic kidney 293 cells were treated with or without (control) several concentrations of TNF-α and DEX for 24 h before measurements of the oxygen consumption rate (OCR) under basal conditions and with the addition of oligomycin, carbonylcyanide-p-trifluoromethoxyphenylhydrazone, antimycin A, and rotenone, as well as intracellular reactive oxygen species (ROS) levels.

RESULTS:

DEX attenuated LPS-induced increases in serum creatinine and IL-6 concentrations. LPS administration caused histological tissue damage in the kidney, but DEX prevented such damage. In vitro, DEX suppressed TNF-α-induced increases in basal OCR and ROS levels and inhibited decreases of ATP production induced by TNF-α.

CONCLUSION:

DEX has protective effects for cells and tissues of the kidney by inhibiting oxygen consumption and hypoxia or by improving mitochondrial dysfunction via TNF-α in the renal cells. These results might point to DEX being an important new therapeutic target for the treatment of septic AKI.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lipopolysaccharides / Dexmedetomidine / Acute Kidney Injury / Mitochondria Type of study: Clinical_trials Limits: Animals / Humans / Male Language: En Journal: Biomed Pharmacother Year: 2020 Document type: Article Affiliation country: Japón

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lipopolysaccharides / Dexmedetomidine / Acute Kidney Injury / Mitochondria Type of study: Clinical_trials Limits: Animals / Humans / Male Language: En Journal: Biomed Pharmacother Year: 2020 Document type: Article Affiliation country: Japón