Quinacrine protects neuronal cells against heat‐induced injury

Abstract

The effects of quinacrine (QA) on heat-induced neuronal injury have been explored, with the intention of understanding the mechanisms of QA protection. Primary cultivated striatum neurons from newborn rats were treated with QA 1h before heat treatment at 43 degrees C which lasted for another 1h, and necrosis and apoptosis were detected by Annexin-V-FITC and propidium iodide (PI) double staining. Neuronal apoptosis was determined using terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) techniques. Cell membrane fluidity, activity of cytosolic phospholipase A(2) (cPLA(2)) and the level of arachidonic acid (AA) were also examined. Membrane surface ultrastructure of striatum neurons was investigated by atomic force microscopy (AFM). Results showed that heat treatment induced great striatum neurons death, with many dying neurons undergoing necrosis rather than apoptosis. QA alone had little effect on the survival of striatum neurons, while QA pretreatment before heat treatment decreased necrosis. Heat treatment also resulted in decreased membrane fluidity and increased cPLA(2) activity as well as arachidonic acid level; these effects were reversed by QA pretreatment. QA pretreatment also significantly prevented damage to the membrane surface ultrastructure of heat-treated neurons. These results suggest that QA protects striatum neurons against heat-induced neuronal necrosis, and also demonstrate that inhibition of cPLA(2) activity and stabilization of membranes may contribute to protective effect of quinacrine.

Protective effect of quinacrine against glycerol-induced acute kidney injury in rats

“…Treatment with glycerol is known to significantly disturb the equilibrium between the AA metabolites including vasodilator prostacyclin (PGI2) and vasoconstrictor thromboxane (TxA2) in favor of TxA2 causing impairment of renal blood flow resulting in ischemic injury [ 44 – 46 ]. Quinacrine, a widely used inhibitor of lipolytic enzyme PLA2 has been shown to dose-dependently inhibit lipolytic release of arachidonate and generation of eicosanoids from kidney medulla [ 47 – 49 ]. Besides being a non-selective PLA2 inhibitor quinacrine has also been shown to possess significant cyclooxygenase inhibitory activity [ 50 ].…”

Protective effects of ectoine on articular chondrocytes and cartilage in rats for treating osteoarthritis

“…For example, heatstroke can cause nerve cell and muscle tissue necrosis and damage liver and kidney function. Gao et al [ 18 ] reported that heating primary cultured rat striatal neurons at 43°C for 1 h resulted in abnormal cell membrane phospholipid metabolism and decreased cell membrane fluidity, which affected cell membrane function.…”

Pharmacokinetics of Quinacrine Efflux from Mouse Brain via the P-glycoprotein Efflux Transporter

“…Unfortunately, the survival of the scrapie-infected mice could not be prolonged due to toxicity of the γ-secretase inhibitor. Quinacrine also proved ineffective in mouse models of glioblastoma and heat-induced injury [12], [13].…”

“…In addition to its ability to intercalate into DNA, quinacrine has been reported to regulate transcription factors, including NF-κB, hsp70 and p53 [12], [27], [28], which control immune responses, proliferation, and tumor genesis. Another study suggested that quinacrine protects heat-induced neuronal injury via inhibition of cPLA2 [13]. Interestingly, a multimeric quinacrine conjugate has been reported to inhibit Aβ-amyloid fibril formation [29].…”

“…Quinacrine also works against cutaneous leishmaniasis and Trypanosoma cruzi in vitro [10], [11]. As a nonselective inhibitor of phospholipase A2, quinacrine has thus been suggested as a possible therapeutic for neoplasms and heat-induced injury [12], [13]. Results from another in-vitro study suggested that quinacrine may be a potent compound for treating glioblastomas by inducing autophagic vacuoles leading to tumor cell death [14].…”