Chelatable Fe (II) is generated in the rat kidneys exposed to ischemia and reperfusion, and a divalent metal chelator, 2, 2′-dipyridyl, attenuates the acute ischemia/reperfusion-injury of the kidneys: a histochemical study by the perfusion-Perls and -Turnbull methods

The perfusion-Perls and -Turnbull methods supplemented by diaminobenzidine intensification demonstrated the generation and localization of chelatable Fe (II) which can catalyze the generation of cytotoxic hydroxyl radicals (OH center dot) during the Fenton reaction in rat kidneys exposed to 40 min ischemia or 40 min-ischemia followed by 60 min-reperfusion. The kidneys exposed to 40 min-ischemia showed Fe (II)-deposits largely localized in the deeper half of the cortex, where the deposits densely filled the tubular cell nuclei, with a small amount of them in the cytoplasm of the proximal convoluted tubules (PCT). Intraluminally protruded or exfoliated tubular cell nuclei were also filled with the deposits. The kidneys subjected to 40 min-ischemia/60 min-reperfusion showed a more extensive distribution of Fe (II)-deposits, including most depths of the cortex. Furthermore, there were numerous exfoliated, Fe (II)-positive nuclei surrounded by a small amount of cytoplasm in the lumen of the PCT. These cells appeared to undergo apoptotic cell death since the lumen of strongly dilated, down-stream, proximal straight tubules were obstructed with numerous apoptotic cells in the kidneys exposed to 40 min-ischemia and 24 h-reperfusion. Pretreatment with a divalent metal chelator, 2, 2'-dipyridyl, effectively inhibited Fe (II)-staining, decreased the number of exfoliated cells in the kidneys with 40 min-ischemia/60 m-reperfusion, and decreased the number of apoptotic cells in the kidneys with 40 min-ischemia/24 h-reperfusion. The generation of highly reactive OH center dot during the Fe2+-catalyzed Fenton reaction was suggested to play a crucial role in ischemia/reperfusion-induced kidney injury.