Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice

• Autorzy: Yu G. , Dong X. , Tang K. , Li B. , Li C. , Zhang W. , Wang Y. , Jin Y.
• Języki publikacji: EN

Abstrakty

EN

Background: Inflammation is an important pathogenic component of endotoxemiainduced acute kidney injury (AKI), finally resulting in renal failure. Diacerein is an interleukin-1β (IL-1β) inhibitor used for osteoarthritis treatment by exerting antiinflammatory effects. This study aims to investigate the effects of diacerein on endotoxemia-induced AKI. Methods: Male C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/kg) for 24 h prior to diacerein treatment (15 mg/kg/day) for another 48 h. Mice were examined by histological, molecular and biochemical approaches. Results: LPS administration showed a time-dependent increase of IL-1β expression and secretion in kidney tissues. Diacerein treatment normalized urine volume and osmolarity, reduced blood urea nitrogen (BUN), fractional excretion of sodium (FENa), serum creatinine and osmolarity, and protected renal function in an endotoxemic AKI mice model. In the histopathologic study, diacerein also improved renal tubular damage such as necrosis of the tubular segment. Moreover, diacerein inhibited LPSinduced increase of inflammatory cytokines, such as IL-1β, tumor necrosis factor-α, monocyte chemoattractant protein-1 and nitric oxide synthase 2. In addition, LPS administration markedly decreased aquaporin 1 (AQP1), AQP2, AQP3, Na,K-ATPase α1, apical type 3 Na/H exchanger and Na-K-2Cl cotransporter expression in the kidney, which was reversed by diacerein treatment. We also found that diacerein or IL-1β inhibition prevented the secretion of inflammatory cytokines and the decrease of AQP and sodium transporter expression induced by LPS in HK-2 cells. Conclusion: Our study demonstrates for the first time that diacerein improves renal function efficiently in endotoxemic AKI mice by suppressing inflammation and altering tubular water and sodium handing. These results suggest that diacerein may be a novel therapeutic agent for the treatment of endotoxemic AKI.

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2018
• Tom: 23
• Opis fizyczny: p.1-12,fig.,ref.

Twórcy

autor

Yu G.

• Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China

autor

Dong X.

• Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China

autor

Tang K.

• Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China

autor

Li B.

• Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China

autor

Li C.

• Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China

autor

Zhang W.

• Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China

autor

Wang Y.

• Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China

autor

Jin Y.

• Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China

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Identyfikatory

DOI

10.1186/s11658-018-0107-z