Protective effect of anisodamine in rats with glycerol-induced acute kidney injury

Abstract

Background Anisodamine is used for the treatment of reperfusion injury in various organs. In this study, we investigated the effectiveness and mechanisms of action of anisodamine in promoting recovery from glycerol-induced acute kidney injury (AKI). Methods We compared the protective effects of atropine and anisodamine in the rat model of glycerol-induced AKI. We examined signaling pathways involved in oxidative stress, inflammation and apoptosis, as well as expression of kidney injury molecule-1 (KIM-1). Renal injury was assessed by measuring serum creatinine and urea, and by histologic analysis. Rhabdomyolysis was evaluated by measuring creatine kinase levels, and oxidative stress was assessed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels in kidney tissues. Inflammation was assessed by quantifying interleukin 6 (IL-6) and CD45 expression. Apoptosis and necrosis were evaluated by measuring caspase-3 (including cleaved caspase 3) and RIP3 levels, respectively. Results Glycerol administration resulted in a higher mean histologic damage score, as well as increases in serum creatinine, urea, creatine kinase, reactive oxygen species (ROS), MDA, IL-6, caspase-3 and KIM-1 levels. Furthermore, glycerol reduced kidney tissue SOD activity. All of these markers were significantly improved by anisodamine and atropine. However, the mean histologic damage score and levels of urea, serum creatinine, creatine kinase, ROS and IL-6 were lower in the anisodamine treatment group compared with the atropine treatment group. Conclusion Pretreatment with anisodamine ameliorates renal dysfunction in the rat model of glycerol-induced rhabdomyolytic kidney injury by reducing oxidative stress, the inflammatory response and cell death.

<p>Anisodamine Suppressed the Growth of Hepatocellular Carcinoma Cells, Induced Apoptosis and Regulated the Levels of Inflammatory Factors by Inhibiting NLRP3 Inflammasome Activation</p>

“…The specific mechanism may be by reducing the expression of ER stress markers IRE-1α, CHOP and ATF4, and inhibiting the activation of TXNIP and NLRP3 inflammasome. 11,26 Besides, ANI protected against myocardial ischemia/reperfusion (I/R) injury. Further mechanism analysis showed that the role of ANI in myocardial I/R may be by the inhibition of oxidative stress, inflammatory factors and cardiomyocyte apoptosis via Figure 5 ANI regulates the levels of inflammatory cytokines by inhibiting NLRP3 expression.…”

Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19

“…4) Anisodamine and organs protection: Anisodamine had displayed wide protection in other important organs, which were also affected in the COVID-19 infection. For example, anisodamine had cardioprotective effect through the suppression of cardiomyocytes apoptosis ( 67 ), protected against ischemic stroke via the α7nAChR ( 68 ), ameliorated renal dysfunction by reducing oxidative stress, the inflammatory response and cell death ( 69 ). The α7nAChR is widely distributed in these organs.…”

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

“…Images were acquired with an Olympus DP70 microscopy with a digital camera (Olympus Optical Co, Ltd., Tokyo, Japan). Using ImageJ software v.1.52s (National Institutes of Health, U.S.A.), the swelling, vacuolar degeneration, necrosis and desquamation of tubular epithelial cells were graded using a semi-quantitative scoring method as previously described [13]…”

“…In mice with Shiga toxin-producing Escherichia coli infection, anisodamine administration suppressed TNF-α mRNA expression [12]. In glycerol-induced AKI, anisodamine administration reduced ROS-induced oxidative stress and thus protected against AKI [13]. Therefore, we hypothesized that the natural extract AniHBr prevent kidney from septic injury by suppressing the mitochondrial metabolism and subsequently mitochondrial dysfunction via suppression of oxidative stress and release of inflammatory cytokines.…”