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In the prevention of IRI by glycine in cells and isolated perfused or cold\u2010stored organs (tissues), direct cytoprotection plays a crucial role, most likely by prevention of the formation of pathological plasma membrane pores. Under<jats:italic>in vivo<\/jats:italic>conditions, the mechanism of protection by glycine is less clear, partly due to the physiological presence of the amino acid. Here, inhibition of the inflammatory response in the injured tissue is considered to contribute decisively to the glycine\u2010induced reduction of IRI. However, attenuation of IRI recently achieved in experimental animals by low\u2010dose glycine treatment regimens suggests additional\/other (unknown) protective mechanisms. Despite the convincing experimental evidence and the large therapeutic width of glycine, there are only a few clinical trials on the protection from IRI by glycine with ambivalent results. 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