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Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice.
Cell Mol Biol Lett. 2018; 23:38.CM

Abstract

BACKGROUND

Inflammation is an important pathogenic component of endotoxemia-induced acute kidney injury (AKI), finally resulting in renal failure. Diacerein is an interleukin-1β (IL-1β) inhibitor used for osteoarthritis treatment by exerting anti-inflammatory 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 LPS-induced 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.

Authors+Show Affiliations

1Department of Emergency Surgery, The 1st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province China.2Department 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.2Department 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.2Department 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.2Department 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.2Department 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.2Department 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.2Department 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.2Department 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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30140293

Citation

Yu, Guangzhe, et al. "Inhibition of Inflammation Using Diacerein Markedly Improved Renal Function in Endotoxemic Acute Kidney Injured Mice." Cellular & Molecular Biology Letters, vol. 23, 2018, p. 38.
Yu G, Liu Q, Dong X, et al. Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice. Cell Mol Biol Lett. 2018;23:38.
Yu, G., Liu, Q., Dong, X., Tang, K., Li, B., Liu, C., Zhang, W., Wang, Y., & Jin, Y. (2018). Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice. Cellular & Molecular Biology Letters, 23, 38. https://doi.org/10.1186/s11658-018-0107-z
Yu G, et al. Inhibition of Inflammation Using Diacerein Markedly Improved Renal Function in Endotoxemic Acute Kidney Injured Mice. Cell Mol Biol Lett. 2018;23:38. PubMed PMID: 30140293.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice. AU - Yu,Guangzhe, AU - Liu,Qian, AU - Dong,Xuening, AU - Tang,Kaihong, AU - Li,Bohui, AU - Liu,Chunmei, AU - Zhang,Wenzheng, AU - Wang,Yiduo, AU - Jin,Yingyu, Y1 - 2018/08/16/ PY - 2018/04/29/received PY - 2018/08/06/accepted PY - 2018/8/25/entrez PY - 2018/8/25/pubmed PY - 2018/10/30/medline KW - Acute kidney injury KW - Aquaporins KW - Diacerein KW - Endotoxemia KW - Inflammation KW - Sodium transporters SP - 38 EP - 38 JF - Cellular & molecular biology letters JO - Cell Mol Biol Lett VL - 23 N2 - BACKGROUND: Inflammation is an important pathogenic component of endotoxemia-induced acute kidney injury (AKI), finally resulting in renal failure. Diacerein is an interleukin-1β (IL-1β) inhibitor used for osteoarthritis treatment by exerting anti-inflammatory 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 LPS-induced 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. SN - 1689-1392 UR - https://www.unboundmedicine.com/medline/citation/30140293/Inhibition_of_inflammation_using_diacerein_markedly_improved_renal_function_in_endotoxemic_acute_kidney_injured_mice_ L2 - https://cmbl.biomedcentral.com/articles/10.1186/s11658-018-0107-z DB - PRIME DP - Unbound Medicine ER -