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Protective Effect of Anisodamine Hydrobromide on Lipopolysaccharide-Induced Acute Kidney Injury

Protective Effect of Anisodamine Hydrobromide on Lipopolysaccharide-Induced Acute Kidney Injury

Feng Wan, Xiaoqiang Du, Huan Liu, Xueling He, Ye Zeng

Biosci Rep. 2020 Jun 23;BSR20201812.

PMID: 32573678

Abstract:

Anisodamine hydrobromide (AniHBr) is a Chinese medicine used to treat septic shock. However, whether AniHBr could ameliorate septic acute kidney injury and the underlying mechanism were not investigated. In the present study, eighteen male Sprague-Dawley rats (200 g-250 g) were randomly divided into control, lipopolysaccharide (LPS) and LPS+AniHBr groups. Rats were intravenously administrated with LPS or normal saline (for control). After 4 h, the rats were intravenously administrated with AniHBr (LPS+AniHBr) or normal saline at 4 h intervals. Heamodynamic parameters including blood pressure and heart rate were measured. The histopathologic evaluation of kidney tissues was performed. Lactate, creatine kinase, inflammatory cytokines and oxidative stress indicators were determined. Using Seahorse analysis, the metabolic analysis of mitochondrial stress and glycolytic stress in human renal proximal tubular epithelial cells treated with TNF-α in the presence of AniHBr were performed. AniHBr administration significantly reduced serum creatine kinase and lactate following LPS treatment. AniHBr significantly improved heamodynamics in sepsis rats including increase of the mean atrial pressure and reduction of the heart rate. AniHBr significantly attenuated LPS-induced TNF-α, IL-6 and IL-1β in serum, and LPS-induced TNF-α and IL-1β in renal tissues. The LPS-reduced SOD activity and LPS-increased MDA content were reversed by AniHBr. In vitro, TNF-α increased mitochondrial oxygen consumption and glycolysis, but inhibited the ATP generation, which was reversed by AniHBr. Thus, AniHBr protects against the LPS-induced inflammatory cytokines, mitochondrial dysfunction and oxidative stress, and thus attenuates the LPS-induced acute kidney injury, showing AniHBr is a promising therapeutic drug for septic kidney injury.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP55449495	Anisodamine hydrobromide		55449-49-5	Price

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