Protective effect of anisodamine hydrobromide on lipopolysaccharide-induced acute kidney injury

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, 18 male Sprague-Dawley rats (200–250 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. Hemodynamic 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 was performed. AniHBr administration significantly reduced serum creatine kinase and lactate following LPS treatment. AniHBr significantly improved hemodynamics in sepsis rats including increase in the mean atrial pressure and reduction in 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.

The effects of l-carnitine supplementation on inflammatory factors, oxidative stress, and clinical outcomes in patients with sepsis admitted to the intensive care unit (ICU): study protocol for a double blind, randomized, placebo-controlled clinical trial

“…Some other anti-inflammatory agents that may also be used in sepsis include ulinastatin, which is a serine protease inhibitor that can reduce IL-6, IL-8, TNF-α, and CRP and can alleviate injury of mitochondria and has anti-oxidant effects; thymosin α-1 (Tα1), which is a thymic peptide regulates immune system and so can decrease mortality rate in septic patients [ 14 ]; and anisodamine, another medicinal treatment choice for septic shock. It improves blood circulation and reduces TNFα in these patients [ 15 ]; besides, anisodamine can combat oxidative agents, act as anti-oxidant, and prevent mitochondrial damage [ 16 ].…”

Construction and Validation of Prognostic Models in Critically Ill Patients with Sepsis-associated Acute Kidney Injury: machine learning approaches compare with traditional logistic regression.

“…That is the mortality of S-AKI patients with severe hyperlactatemia was considerably higher than the remaining. In the practice of clinical, serum lactate level, as a sensitive indicator to diagnose whether it is in a status of hypoperfusion or hypoxia, has also been shown to correlate with the severity and prognosis of sepsis [42][43][44]. Lactate and bicarbonate are both typical metabolic indicators.…”

Anisodamine hydrobromide attenuates oxidative stress and proinflammatory cytokines in septic rats induced by cecal ligation and puncture

“…NF-κB plays an important role in inflammatory illnesses by regulating the production of pro-inflammatory cytokines (25). Ani HBr has been reported to reduce LPS-induced acute kidney injury by inhibiting lipopolysaccharide-induced inflammatory cytokines, mitochondrial dysfunction, and oxidative stress (26). These findings revealed that anisodamine's anti-shock action was partially associated with anti-inflammation (27).…”