In summary, on the basis of results present herein, it is possible to suggest that pharmacological inhibition of CXCR2 receptors by the antagonist SB225002 is able to interfere, in a dose-dependent manner, with paraquat-related systemic toxicity. Further studies are necessary to reinforce our findings. Cholesterol is a vital constituent in the plasma membrane of higher eukaryotes, where it typically represents 25–40% of total lipids. Cholesterol regulates biophysical membrane properties such as fluidity, permeability, and rigidity. It interacts with neighbouring lipids and proteins via steric interactions and via hydrogen bonding through its 3b-hydroxyl group. The interactions between cholesterol and polar phospholipids can locally increase lipid order. This leads to the formation of dynamic membrane domains that contribute to the regulation of key cellular processes, such as receptor signaling, endocytosis and cell polarity. To assess the functional importance of cholesterol, membrane cholesterol content is often reduced experimentally. Typically, cholesterol is extracted using methyl-b-cyclodextrin, which can deplete up to 80–90% of plasma membrane cholesterol. Another commonly used method is to expose the membrane to purified bacterial cholesterol oxidase. Enzymatic cholesterol oxidation and cholesterol removal by MBCD are often used interchangeably for cholesterol reduction but they act via different mechanisms; MBCD extrudes cholesterol from the membrane, whereas coase catalyzes the conversion of up to,20% of cellular cholesterol to 4-cholesten-3-one. Cholesterol oxidizing bacteria can further catabolize cholestenone to use it as their nutritional hydrocarbon source. However, in mammals, cholestenone is metabolized primarily in the liver. Therefore, once generated, cholestenone is likely to persist in extrahepatic mammalian cells. In cholestenone, the steroid 3-hydroxyl group is replaced by a keto group, with a more limited capacity for hydrogen bonding than a hydroxyl group. Consequently, cholestenone preferentially localizes to liquid-disordered domains in model membranes and causes lipid monolayer expansion. While coase treatment is widely used to disturb cholesterol domains in cell membranes, the membrane partitioning and effects of cholestenone in the cellular context have so far received little attention. In this study, we characterized the effects of coase treatment on membrane order and steroid mobility in primary human dermal fibroblasts. The molecular interactions PF-4217903 involved in cholestenone membrane partitioning and desorption from the membrane were addressed using atomistic simulations. Our data suggest that cholestenone is highly mobile in membranes and influences cholesterol flip-flop and efflux. Moreover, we provide evidence that in contrast to MBCD induced cholesterol depletion cholesterol oxidation causes long-term functional defects in cells due to the persistence of cholestenone. Atomistic MD simulations were also used to analyse how cholestenone affects the movement of the steroid molecules between membrane leaflets. One of the most striking observations was the frequent occurrence of inter-leaflet movements or flip-flop motions of cholestenone molecules.